PKHD1_HUMAN
ID PKHD1_HUMAN Reviewed; 4074 AA.
AC P08F94; Q5VUA2; Q5VUA3; Q5VWV1; Q86Z26; Q8TCZ9;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Fibrocystin {ECO:0000305};
DE AltName: Full=Polycystic kidney and hepatic disease 1 protein;
DE AltName: Full=Polyductin;
DE AltName: Full=Tigmin;
DE Flags: Precursor;
GN Name=PKHD1 {ECO:0000303|PubMed:28375157, ECO:0000312|HGNC:HGNC:9016};
GN Synonyms=FCYT, TIGM1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS PKD4 MET-36;
RP VAL-222; TRP-1249; ARG-1407; PHE-1664; MET-1741; ARG-1917; GLY-1995;
RP LYS-2331; THR-2957; PHE-3018 AND THR-3553, AND VARIANTS VAL-25; MET-752;
RP CYS-760; ARG-852; VAL-1262; MET-2938; TYR-3139; ILE-3960 AND ARG-4048.
RC TISSUE=Kidney;
RX PubMed=11919560; DOI=10.1038/ng833;
RA Ward C.J., Hogan M.C., Rossetti S., Walker D., Sneddon T., Wang X.,
RA Kubly V., Cunningham J.M., Bacallao R., Ishibashi M., Milliner D.S.,
RA Torres V.E., Harris P.C.;
RT "The gene mutated in autosomal recessive polycystic kidney disease encodes
RT a large, receptor-like protein.";
RL Nat. Genet. 30:259-269(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE SPLICING,
RP VARIANTS PKD4 MET-36; VAL-222; LEU-253; HIS-760; SER-1122; TRP-1624 AND
RP THR-2957, AND VARIANTS VAL-1870 AND TYR-3139.
RC TISSUE=Kidney;
RX PubMed=11898128; DOI=10.1086/340448;
RA Onuchic L.F., Furu L., Nagasawa Y., Hou X., Eggermann T., Ren Z.,
RA Bergmann C., Senderek J., Esquivel E., Zeltner R., Rudnik-Schoeneborn S.,
RA Mrug M., Sweeney W., Avner E.D., Zerres K., Guay-Woodford L.M., Somlo S.,
RA Germino G.G.;
RT "PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel
RT large protein containing multiple immunoglobulin-like-plexin-transcription-
RT factor domains and parallel beta-helix 1 repeats.";
RL Am. J. Hum. Genet. 70:1305-1317(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT TYR-1204.
RC TISSUE=Fetal kidney;
RX PubMed=12079288; DOI=10.1006/geno.2002.6802;
RA Xiong H., Chen Y., Yi Y., Tsuchiya K., Moeckel G., Cheung J., Liang D.,
RA Tham K., Xu X., Chen X.-Z., Pei Y., Zhao Z.J., Wu G.;
RT "A novel gene encoding a TIG multiple domain protein is a positional
RT candidate for autosomal recessive polycystic kidney disease.";
RL Genomics 80:96-104(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=14978161; DOI=10.1097/01.asn.0000113793.12558.1d;
RA Wang S., Luo Y., Wilson P.D., Witman G.B., Zhou J.;
RT "The autosomal recessive polycystic kidney disease protein is localized to
RT primary cilia, with concentration in the basal body area.";
RL J. Am. Soc. Nephrol. 15:592-602(2004).
RN [7]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15458427; DOI=10.1111/j.1523-1755.2004.00844.x;
RA Menezes L.F., Cai Y., Nagasawa Y., Silva A.M., Watkins M.L., Da Silva A.M.,
RA Somlo S., Guay-Woodford L.M., Germino G.G., Onuchic L.F.;
RT "Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma
RT membrane, primary cilium, and cytoplasm.";
RL Kidney Int. 66:1345-1355(2004).
RN [8]
RP MUTAGENESIS OF 3617-LYS-ARG-3618, PROTEOLYTIC PROCESSING, CLEAVAGE SITE,
RP SHEDDING, AND SUBCELLULAR LOCATION.
RX PubMed=17470460; DOI=10.1093/hmg/ddm039;
RA Kaimori J.Y., Nagasawa Y., Menezes L.F., Garcia-Gonzalez M.A., Deng J.,
RA Imai E., Onuchic L.F., Guay-Woodford L.M., Germino G.G.;
RT "Polyductin undergoes notch-like processing and regulated release from
RT primary cilia.";
RL Hum. Mol. Genet. 16:942-956(2007).
RN [9]
RP INTERACTION WITH PKD2.
RX PubMed=18235088; DOI=10.1681/asn.2007070770;
RA Kim I., Fu Y., Hui K., Moeckel G., Mai W., Li C., Liang D., Zhao P., Ma J.,
RA Chen X.Z., George A.L. Jr., Coffey R.J., Feng Z.P., Wu G.;
RT "Fibrocystin/polyductin modulates renal tubular formation by regulating
RT polycystin-2 expression and function.";
RL J. Am. Soc. Nephrol. 19:455-468(2008).
RN [10]
RP INTERACTION WITH CAMLG.
RX PubMed=16243292; DOI=10.1016/j.bbrc.2005.10.022;
RA Nagano J., Kitamura K., Hujer K.M., Ward C.J., Bram R.J., Hopfer U.,
RA Tomita K., Huang C., Miller R.T.;
RT "Fibrocystin interacts with CAML, a protein involved in Ca2+ signaling.";
RL Biochem. Biophys. Res. Commun. 338:880-889(2005).
RN [11]
RP PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=16956880; DOI=10.1074/jbc.m606740200;
RA Hiesberger T., Gourley E., Erickson A., Koulen P., Ward C.J., Masyuk T.V.,
RA Larusso N.F., Harris P.C., Igarashi P.;
RT "Proteolytic cleavage and nuclear translocation of fibrocystin is regulated
RT by intracellular Ca2+ and activation of protein kinase C.";
RL J. Biol. Chem. 281:34357-34364(2006).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20554582; DOI=10.1093/hmg/ddq233;
RA Zhang J., Wu M., Wang S., Shah J.V., Wilson P.D., Zhou J.;
RT "Polycystic kidney disease protein fibrocystin localizes to the mitotic
RT spindle and regulates spindle bipolarity.";
RL Hum. Mol. Genet. 19:3306-3319(2010).
RN [13]
RP FUNCTION.
RX PubMed=30898581; DOI=10.1016/j.jhep.2019.02.024;
RA Tsunoda T., Kakinuma S., Miyoshi M., Kamiya A., Kaneko S., Sato A.,
RA Tsuchiya J., Nitta S., Kawai-Kitahata F., Murakawa M., Itsui Y.,
RA Nakagawa M., Azuma S., Sogo T., Komatsu H., Mukouchi R., Inui A.,
RA Fujisawa T., Nakauchi H., Asahina Y., Watanabe M.;
RT "Loss of fibrocystin promotes interleukin-8-dependent proliferation and
RT CTGF production of biliary epithelium.";
RL J. Hepatol. 71:143-152(2019).
RN [14]
RP VARIANTS PKD4 MET-36; SER-223; LEU-253; SER-473; PRO-496; CYS-656; ASN-703;
RP HIS-760; LEU-805; LYS-997; GLU-1030; SER-1122; SER-1123; TRP-1249;
RP ARG-1407; LEU-1486; TRP-1624; PHE-1664; MET-1741; ARG-1917; GLY-1995;
RP THR-1998; PRO-2134; LYS-2331; TYR-2761; THR-2957; PHE-3018; VAL-3081;
RP VAL-3293; GLY-3471; CYS-3482 AND THR-3553, AND VARIANTS MET-579; SER-830
RP AND TYR-3139.
RX PubMed=12506140; DOI=10.1097/01.asn.0000039578.55705.6e;
RA Bergmann C., Senderek J., Sedlacek B., Pegiazoglou I., Puglia P.,
RA Eggermann T., Rudnik-Schoeneborn S., Furu L., Onuchic L.F., De Baca M.,
RA Germino G.G., Guay-Woodford L., Somlo S., Moser M., Buettner R., Zerres K.;
RT "Spectrum of mutations in the gene for autosomal recessive polycystic
RT kidney disease (ARPKD/PKHD1).";
RL J. Am. Soc. Nephrol. 14:76-89(2003).
RN [15]
RP VARIANTS PKD4 MET-36; VAL-326; ASN-387 DEL; PRO-899; SER-1123; ILE-1584;
RP ILE-1781; LEU-1789; GLY-1942; ASP-1971; LEU-2032; GLY-2422; PRO-2772;
RP CYS-2863; THR-2957; LEU-2983; GLY-3036; TYR-3124; LEU-3167; ASP-3175;
RP SER-3175; THR-3177; VAL-3293 AND SER-3783, AND VARIANTS ASP-457; PHE-732;
RP CYS-760; PRO-1150; LEU-1283; PHE-1709; VAL-1870; GLY-2615; ALA-2641;
RP GLY-2861; LYS-2869; TYR-3139; ILE-3143; ASP-3440; LYS-3551; ARG-3899 AND
RP ILE-3960.
RX PubMed=12874454; DOI=10.1097/01.asn.0000078805.87038.05;
RA Furu L., Onuchic L.F., Gharavi A., Hou X., Esquivel E.L., Nagasawa Y.,
RA Bergmann C., Senderek J., Avner E., Zerres K., Germino G.G.,
RA Guay-Woodford L.M., Somlo S.;
RT "Milder presentation of recessive polycystic kidney disease requires
RT presence of amino acid substitution mutations.";
RL J. Am. Soc. Nephrol. 14:2004-2014(2003).
RN [16]
RP VARIANTS PKD4 VAL-17; MET-36; VAL-222; LEU-739; LEU-757; LEU-805; THR-1389;
RP MET-1741; LEU-1833; CYS-1838; ASN-1867; GLY-1942; PHE-2688; THR-2957;
RP THR-3177; ARG-3346; VAL-3468; VAL-3502 AND TYR-3622, AND VARIANTS CYS-760;
RP SER-830; VAL-1262; PHE-1709; VAL-1870; LYS-2869; TYR-3139; ARG-3505;
RP GLN-3529; ARG-3899; ILE-3960 AND ARG-4048.
RX PubMed=12846734; DOI=10.1046/j.1523-1755.2003.00111.x;
RA Rossetti S., Torra R., Coto E., Consugar M., Kubly V., Malaga S.,
RA Navarro M., El-Youssef M., Torres V.E., Harris P.C.;
RT "A complete mutation screen of PKHD1 in autosomal-recessive polycystic
RT kidney disease (ARPKD) pedigrees.";
RL Kidney Int. 64:391-403(2003).
RN [17]
RP REVIEW ON VARIANTS.
RX PubMed=15108277; DOI=10.1002/humu.20029;
RA Bergmann C., Senderek J., Kuepper F., Schneider F., Dornia C., Windelen E.,
RA Eggermann T., Rudnik-Schoeneborn S., Kirfel J., Furu L., Onuchic L.F.,
RA Rossetti S., Harris P.C., Somlo S., Guay-Woodford L., Germino G.G.,
RA Moser M., Buettner R., Zerres K.;
RT "PKHD1 mutations in autosomal recessive polycystic kidney disease
RT (ARPKD).";
RL Hum. Mutat. 23:453-463(2004).
RN [18]
RP VARIANTS PKD4 MET-36; THR-307; HIS-486; LEU-805; TYR-1472; PHE-2303;
RP THR-2957; GLY-2962; TYR-3124; THR-3177 AND CYS-3482, AND VARIANTS LYS-2869
RP AND TYR-3139.
RX PubMed=15108281; DOI=10.1002/humu.20019;
RA Bergmann C., Senderek J., Schneider F., Dornia C., Kuepper F.,
RA Eggermann T., Rudnik-Schoeneborn S., Kirfel J., Moser M., Buettner R.,
RA Zerres K.;
RT "PKHD1 mutations in families requesting prenatal diagnosis for autosomal
RT recessive polycystic kidney disease (ARPKD).";
RL Hum. Mutat. 23:487-495(2004).
RN [19]
RP VARIANT PKD4 LEU-372.
RX PubMed=16677362; DOI=10.1111/j.1399-3046.2005.00464.x;
RA Prelog M., Bergmann C., Ausserlechner M.J., Fischer H., Margreiter R.,
RA Gassner I., Brunner A., Jungraithmayr T.C., Zerres K., Sergi E.C.,
RA Zimmerhackl L.B.;
RT "Successful transplantation in a child with rapid progression of autosomal
RT recessive polycystic kidney disease associated with a novel mutation.";
RL Pediatr. Transplant. 10:362-366(2006).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-19; CYS-1081; ARG-1096; TRP-1624 AND
RP LYS-1806.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [21]
RP VARIANTS PKD4 TRP-92; THR-246; CYS-255; VAL-293; GLU-466; VAL-470; THR-539;
RP PRO-686; ARG-724; ARG-1712; GLY-1817; GLY-1875; LEU-1928; THR-2009;
RP ARG-2106; GLU-2210; LEU-2219; ARG-2224; ARG-2422; VAL-2431; CYS-2573;
RP GLY-2798; ARG-2803; LYS-2804; ARG-3049; THR-3207 AND CYS-3957, AND VARIANTS
RP VAL-292; CYS-723; HIS-2661 AND ALA-3219.
RX PubMed=19914852; DOI=10.1016/j.ymgme.2009.10.010;
RA Gunay-Aygun M., Tuchman M., Font-Montgomery E., Lukose L., Edwards H.,
RA Garcia A., Ausavarat S., Ziegler S.G., Piwnica-Worms K., Bryant J.,
RA Bernardini I., Fischer R., Huizing M., Guay-Woodford L., Gahl W.A.;
RT "PKHD1 sequence variations in 78 children and adults with autosomal
RT recessive polycystic kidney disease and congenital hepatic fibrosis.";
RL Mol. Genet. Metab. 99:160-173(2010).
RN [22]
RP VARIANTS PKD4 HIS-19; MET-36; LYS-218; VAL-222; TRP-1624; TRP-1624;
RP THR-2957 AND ILE-3289, AND VARIANTS MET-579; SER-830 AND LYS-2869.
RX PubMed=25701400; DOI=10.1016/j.gene.2015.02.040;
RA Tavira B., Gomez J., Malaga S., Santos F., Fernandez-Aracama J., Alonso B.,
RA Iglesias S., Benavides A., Hernando I., Plasencia A., Alvarez V., Coto E.;
RT "A labor and cost effective next generation sequencing of PKHD1 in
RT autosomal recessive polycystic kidney disease patients.";
RL Gene 561:165-169(2015).
RN [23]
RP VARIANTS MET-36; 496-ARG--LEU-4074 DEL; ILE-2436; SER-2648; TYR-3024;
RP 3070-GLN--LEU-4074 DEL; CYS-3210; ALA-3263; 3407-GLN--LEU-4074 DEL;
RP SER-3780; 4009-TYR--LEU-4074 DEL; PRO-4037 AND 4048-GLN--LEU-4074 DEL.
RX PubMed=28375157; DOI=10.1172/jci90129;
RA Besse W., Dong K., Choi J., Punia S., Fedeles S.V., Choi M.,
RA Gallagher A.R., Huang E.B., Gulati A., Knight J., Mane S., Tahvanainen E.,
RA Tahvanainen P., Sanna-Cherchi S., Lifton R.P., Watnick T., Pei Y.P.,
RA Torres V.E., Somlo S.;
RT "Isolated polycystic liver disease genes define effectors of polycystin-1
RT function.";
RL J. Clin. Invest. 127:1772-1785(2017).
CC -!- FUNCTION: Promotes ciliogenesis in renal epithelial cells and therefore
CC participates in the tubules formation and/ or ensures the maintenance
CC of the architecture of the lumen of the kidney (By similarity). Has an
CC impact on cellular symmetry by ensuring correct bipolar cell division
CC through the regulation of centrosome duplication and mitotic spindle
CC assembly and by maintaining oriented cell division (OCD) during tubular
CC elongation through planar cell polarity (PCP) pathway
CC (PubMed:20554582). During epithelial cell morphogenesis regulates also
CC cell-cell and cell-matrix adhesion and participates in cell motility
CC (By similarity). Promotes cell-cell contact through the positive
CC regulation of PTK2 kinase activity leading to either positive
CC regulation of epithelial cell proliferation through the HRAS/RAF1
CC pathways, or negative regulation of apoptosis through the PDK1/AKT1
CC pathway (By similarity). May act in collecting-duct and biliary
CC differentiation (PubMed:11919560). May participate in the regulation of
CC the cholangiocytes proliferation and the CCN2 production in an CXCL8-
CC dependent manner (PubMed:30898581). {ECO:0000250|UniProtKB:E2RK30,
CC ECO:0000250|UniProtKB:E9PZ36, ECO:0000269|PubMed:11919560,
CC ECO:0000269|PubMed:20554582, ECO:0000269|PubMed:30898581}.
CC -!- SUBUNIT: Interacts with CAMLG (PubMed:16243292). Interacts with PKD2
CC (PubMed:18235088). Interacts (via CST) with ARF4; this interaction
CC allows an efficient PKHD1 trafficking to the cilium. Interacts (via
CC CST) with RAB8A; this interaction controls trafficking through the
CC endomembrane systeme and the cilium. Interacts (via CST) with TULP3;
CC this interaction allows PKHD1 trafficking to the cilium (By
CC similarity). {ECO:0000250|UniProtKB:E9PZ36,
CC ECO:0000269|PubMed:16243292, ECO:0000269|PubMed:18235088}.
CC -!- INTERACTION:
CC P08F94; P49069: CAMLG; NbExp=3; IntAct=EBI-11693144, EBI-1748958;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15458427};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000269|PubMed:15458427}. Cell projection, cilium
CC {ECO:0000269|PubMed:14978161, ECO:0000269|PubMed:15458427,
CC ECO:0000269|PubMed:17470460}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:14978161}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:20554582}. Chromosome, centromere
CC {ECO:0000269|PubMed:20554582}. Apical cell membrane
CC {ECO:0000250|UniProtKB:E9PZ36}. Nucleus {ECO:0000250|UniProtKB:E9PZ36}.
CC Secreted, extracellular exosome {ECO:0000250|UniProtKB:E9PZ36}.
CC Secreted {ECO:0000250|UniProtKB:E9PZ36}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:E9PZ36}. Golgi apparatus
CC {ECO:0000250|UniProtKB:E9PZ36}. Note=The intracellular C-terminal
CC fragment (ICD) translocates to the nucleus and is not detected in
CC primary cilia (PubMed:17470460, PubMed:16956880). The extracellular
CC domain (PECD) traffics beyond the mid-Golgi and localizes on exosome
CC like vesicles (ELVs) attached to the primary cilium (By similarity). In
CC the urine, the extracellular domain (PECD) exists as an highly abundant
CC secreted form and a less abundant PECD form that is either tethered to
CC or shed with the C-terminal fragment (PTM) in ELVs (By similarity). The
CC majority of full length PKHD1 protein resides at the endoplasmic
CC reticulum and cannot pass beyond the mid-Golgi apparatus and is not
CC detected in primary cilia (By similarity). The intra-cellular C-
CC terminal fragment of 21-kDa translocates to the nucleus. The
CC extracellular domain traffics beyond the mid-Golgi and localizes on
CC exosome like vesicles (ELVs) attached to the primary cilium (By
CC similarity). {ECO:0000250|UniProtKB:E9PZ36,
CC ECO:0000269|PubMed:16956880, ECO:0000269|PubMed:17470460}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist. As a matter of fact,
CC alternatively spliced products seem to fall into two broad groups:
CC one group, which includes the longest continuous ORF but which may
CC also include molecules lacking some middle domains, has a single TM
CC element and is likely to be associated with the plasma membrane. The
CC other group lacks a TM domain and thus its members may be secreted.;
CC Name=1;
CC IsoId=P08F94-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08F94-2; Sequence=VSP_003947, VSP_003948;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in fetal and adult kidney.
CC In the kidney, it is found in the cortical and medullary collecting
CC ducts. Also present in the adult pancreas, but at much lower levels.
CC Detectable in fetal and adult liver. Rather indistinct signal in fetal
CC brain. {ECO:0000269|PubMed:14978161, ECO:0000269|PubMed:15458427}.
CC -!- PTM: Several proteolytic cleavages occur within the extracellular
CC domain, whereas at least one cleavage occurs within the cytoplasmic
CC domain (PubMed:16956880). Cleaved by a probable proprotein convertase
CC which produces an extracellular domain (polyductin extracellular
CC domain, (PECD)) and a C-terminal fragment (polyductin transmembrane
CC fragment (PTM)) which are tethered together by disulfide bonds
CC (PubMed:17470460). This extracellular domain (PECD) is then shed from
CC the primary cilium by activation of a member of the ADAM
CC metalloproteinase disintegrins family, resulting in concomitant release
CC of an intra-cellular C-terminal fragment (ICD) via a gamma-secretase-
CC dependent process (PubMed:17470460). The proteolytic cleavage of the C-
CC terminal intracellular fragment (ICD) is controlled by cytosolic
CC calcium concentration and activation of PKC (PubMed:16956880).
CC {ECO:0000269|PubMed:16956880, ECO:0000269|PubMed:17470460}.
CC -!- PTM: Palmitoylated. Palmitoylation facilitates membrane targeting and
CC the trafficking to the cilia. {ECO:0000250|UniProtKB:E9PZ36}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:E9PZ36}.
CC -!- DISEASE: Polycystic kidney disease 4, with or without polycystic liver
CC disease (PKD4) [MIM:263200]: A severe form of polycystic kidney disease
CC affecting the kidneys and, in some cases, the hepatic biliary tract.
CC The clinical spectrum is widely variable, with most cases presenting
CC during infancy. The fetal phenotypic features classically include
CC enlarged and echogenic kidneys, as well as oligohydramnios secondary to
CC a poor urine output. Up to 50% of the affected neonates die shortly
CC after birth, as a result of severe pulmonary hypoplasia and secondary
CC respiratory insufficiency. In the subset that survives the perinatal
CC period, morbidity and mortality are mainly related to severe systemic
CC hypertension, renal insufficiency, and portal hypertension due to
CC portal-tract fibrosis. PKD4 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11898128, ECO:0000269|PubMed:11919560,
CC ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:12846734,
CC ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281,
CC ECO:0000269|PubMed:16677362, ECO:0000269|PubMed:19914852,
CC ECO:0000269|PubMed:25701400}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Loss-of-function PKHD1 variations may cause autosomal
CC dominant polycystic liver disease (PCLD) in patients that lack
CC variations in known causative genes, such as PRKCSH and SEC63.
CC {ECO:0000269|PubMed:28375157}.
CC -!- WEB RESOURCE: Name=Mutation Database Autosomal Recessive Polycystic
CC Kidney Disease (ARPKD/PKHD1);
CC URL="http://www.humgen.rwth-aachen.de/";
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DR EMBL; AY074797; AAL74290.1; -; mRNA.
DR EMBL; AY129465; AAM93492.1; -; Genomic_DNA.
DR EMBL; AF480064; AAM44232.1; -; mRNA.
DR EMBL; AY092083; AAM18186.1; -; mRNA.
DR EMBL; AL590391; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355997; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04359.1; -; Genomic_DNA.
DR CCDS; CCDS4935.1; -. [P08F94-1]
DR CCDS; CCDS4936.1; -. [P08F94-2]
DR RefSeq; NP_619639.3; NM_138694.3. [P08F94-1]
DR RefSeq; NP_733842.2; NM_170724.2. [P08F94-2]
DR RefSeq; XP_011512982.1; XM_011514680.2. [P08F94-1]
DR RefSeq; XP_016866433.1; XM_017010944.1. [P08F94-1]
DR BioGRID; 111331; 9.
DR CORUM; P08F94; -.
DR IntAct; P08F94; 3.
DR STRING; 9606.ENSP00000360158; -.
DR GlyGen; P08F94; 64 sites.
DR iPTMnet; P08F94; -.
DR PhosphoSitePlus; P08F94; -.
DR BioMuta; PKHD1; -.
DR DMDM; 296439717; -.
DR EPD; P08F94; -.
DR MassIVE; P08F94; -.
DR PaxDb; P08F94; -.
DR PeptideAtlas; P08F94; -.
DR PRIDE; P08F94; -.
DR ProteomicsDB; 52181; -. [P08F94-1]
DR ProteomicsDB; 52182; -. [P08F94-2]
DR Antibodypedia; 30875; 167 antibodies from 13 providers.
DR DNASU; 5314; -.
DR Ensembl; ENST00000340994.4; ENSP00000341097.4; ENSG00000170927.15. [P08F94-2]
DR Ensembl; ENST00000371117.8; ENSP00000360158.3; ENSG00000170927.15. [P08F94-1]
DR GeneID; 5314; -.
DR KEGG; hsa:5314; -.
DR MANE-Select; ENST00000371117.8; ENSP00000360158.3; NM_138694.4; NP_619639.3.
DR UCSC; uc003pah.2; human. [P08F94-1]
DR CTD; 5314; -.
DR DisGeNET; 5314; -.
DR GeneCards; PKHD1; -.
DR GeneReviews; PKHD1; -.
DR HGNC; HGNC:9016; PKHD1.
DR HPA; ENSG00000170927; Group enriched (epididymis, kidney, pancreas).
DR MalaCards; PKHD1; -.
DR MIM; 263200; phenotype.
DR MIM; 606702; gene.
DR neXtProt; NX_P08F94; -.
DR OpenTargets; ENSG00000170927; -.
DR Orphanet; 731; Autosomal recessive polycystic kidney disease.
DR Orphanet; 53035; Caroli disease.
DR PharmGKB; PA33348; -.
DR VEuPathDB; HostDB:ENSG00000170927; -.
DR eggNOG; ENOG502QR85; Eukaryota.
DR GeneTree; ENSGT00940000160697; -.
DR HOGENOM; CLU_000057_1_0_1; -.
DR InParanoid; P08F94; -.
DR OMA; ETVHNAD; -.
DR OrthoDB; 323806at2759; -.
DR PhylomeDB; P08F94; -.
DR TreeFam; TF329582; -.
DR PathwayCommons; P08F94; -.
DR SignaLink; P08F94; -.
DR BioGRID-ORCS; 5314; 11 hits in 1070 CRISPR screens.
DR ChiTaRS; PKHD1; human.
DR GenomeRNAi; 5314; -.
DR Pharos; P08F94; Tbio.
DR PRO; PR:P08F94; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P08F94; protein.
DR Bgee; ENSG00000170927; Expressed in kidney epithelium and 42 other tissues.
DR Genevisible; P08F94; HS.
DR GO; GO:0097731; C:9+0 non-motile cilium; IEA:Ensembl.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; TAS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0045216; P:cell-cell junction organization; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IEA:Ensembl.
DR GO; GO:0003382; P:epithelial cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0051660; P:establishment of centrosome localization; ISS:UniProtKB.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISS:UniProtKB.
DR GO; GO:0042592; P:homeostatic process; NAS:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0010824; P:regulation of centrosome duplication; IMP:UniProtKB.
DR GO; GO:1904054; P:regulation of cholangiocyte proliferation; IMP:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0090175; P:regulation of establishment of planar polarity; ISS:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB.
DR Gene3D; 2.160.20.10; -; 2.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR039448; Beta_helix.
DR InterPro; IPR019316; G8_domain.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR037524; PA14/GLEYA.
DR InterPro; IPR006626; PbH1.
DR InterPro; IPR012334; Pectin_lyas_fold.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR InterPro; IPR028839; PKHD1.
DR PANTHER; PTHR46769:SF1; PTHR46769:SF1; 1.
DR Pfam; PF13229; Beta_helix; 2.
DR Pfam; PF10162; G8; 2.
DR Pfam; PF01833; TIG; 7.
DR SMART; SM01225; G8; 2.
DR SMART; SM00429; IPT; 6.
DR SMART; SM00710; PbH1; 10.
DR SUPFAM; SSF51126; SSF51126; 2.
DR SUPFAM; SSF81296; SSF81296; 6.
DR PROSITE; PS51484; G8; 2.
DR PROSITE; PS51820; PA14; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Centromere;
KW Chromosome; Ciliopathy; Cilium; Cytoplasm; Cytoskeleton; Disease variant;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Membrane; Nucleus;
KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..4074
FT /note="Fibrocystin"
FT /id="PRO_0000022062"
FT TOPO_DOM 24..3858
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 3859..3879
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3880..4074
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..111
FT /note="IPT/TIG 1; atypical"
FT DOMAIN 137..232
FT /note="IPT/TIG 2"
FT DOMAIN 259..335
FT /note="IPT/TIG 3"
FT DOMAIN 322..485
FT /note="PA14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01164"
FT DOMAIN 931..1015
FT /note="IPT/TIG 4"
FT DOMAIN 1019..1103
FT /note="IPT/TIG 5"
FT DOMAIN 1108..1192
FT /note="IPT/TIG 6; atypical"
FT DOMAIN 1196..1289
FT /note="IPT/TIG 7"
FT DOMAIN 1301..1382
FT /note="IPT/TIG 8; atypical"
FT DOMAIN 1389..1481
FT /note="IPT/TIG 9"
FT DOMAIN 1486..1570
FT /note="IPT/TIG 10"
FT DOMAIN 1573..1659
FT /note="IPT/TIG 11"
FT DOMAIN 1658..1742
FT /note="IPT/TIG 12; atypical"
FT DOMAIN 1932..2053
FT /note="G8 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817"
FT REPEAT 2226..2248
FT /note="PbH1 1"
FT REPEAT 2249..2271
FT /note="PbH1 2"
FT REPEAT 2292..2325
FT /note="PbH1 3"
FT REPEAT 2326..2347
FT /note="PbH1 4"
FT REPEAT 2409..2431
FT /note="PbH1 5"
FT REPEAT 2469..2502
FT /note="PbH1 6"
FT DOMAIN 2747..2873
FT /note="G8 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817"
FT REPEAT 3010..3032
FT /note="PbH1 7"
FT REPEAT 3033..3055
FT /note="PbH1 8"
FT REPEAT 3086..3108
FT /note="PbH1 9"
FT REGION 3876..3893
FT /note="Ciliary targeting sequence (CST)"
FT /evidence="ECO:0000250|UniProtKB:E9PZ36"
FT REGION 3890..3925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3952..3976
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000250|UniProtKB:E9PZ36"
FT COMPBIAS 3908..3925
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 3620..3621
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:17470460"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 520
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 711
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 830
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 869
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 967
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 977
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1065
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1084
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1527
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1532
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1582
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1631
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1698
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1764
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1779
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1879
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1883
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1919
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1945
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1959
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2034
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2509
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2553
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2595
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2633
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2753
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2768
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3008
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3707
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3726
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3838
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 3386..3396
FT /note="GTFREEQKCTY -> VTTEQALKISE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12079288"
FT /id="VSP_003947"
FT VAR_SEQ 3397..4074
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12079288"
FT /id="VSP_003948"
FT VARIANT 17
FT /note="A -> V (in PKD4; dbSNP:rs755654557)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018520"
FT VARIANT 19
FT /note="R -> H (in a colorectal cancer sample and PKD4;
FT somatic mutation; unknown pathological significance;
FT dbSNP:rs1375765328)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:25701400"
FT /id="VAR_036228"
FT VARIANT 25
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:11919560"
FT /id="VAR_018521"
FT VARIANT 36
FT /note="T -> M (in PKD4; common mutation; also found in a
FT patient affected by polycystic liver disease;
FT dbSNP:rs137852944)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454,
FT ECO:0000269|PubMed:15108281, ECO:0000269|PubMed:25701400,
FT ECO:0000269|PubMed:28375157"
FT /id="VAR_014039"
FT VARIANT 92
FT /note="R -> W (in PKD4; dbSNP:rs370277502)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066416"
FT VARIANT 218
FT /note="E -> K (in PKD4; unknown pathological significance;
FT dbSNP:rs149522482)"
FT /evidence="ECO:0000269|PubMed:25701400"
FT /id="VAR_075540"
FT VARIANT 222
FT /note="I -> V (in PKD4; dbSNP:rs369925690)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12846734,
FT ECO:0000269|PubMed:25701400"
FT /id="VAR_014040"
FT VARIANT 223
FT /note="G -> S (in PKD4; dbSNP:rs749454235)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018522"
FT VARIANT 246
FT /note="I -> T (in PKD4; dbSNP:rs1037991711)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066417"
FT VARIANT 253
FT /note="F -> L (in PKD4; dbSNP:rs775254013)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014041"
FT VARIANT 255
FT /note="Y -> C (in PKD4; dbSNP:rs886042259)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066418"
FT VARIANT 292
FT /note="I -> V (in a patient with polycystic kidney disease;
FT dbSNP:rs367590965)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066419"
FT VARIANT 293
FT /note="A -> V (in PKD4; dbSNP:rs398124499)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066420"
FT VARIANT 307
FT /note="I -> T (in PKD4; dbSNP:rs1288017883)"
FT /evidence="ECO:0000269|PubMed:15108281"
FT /id="VAR_018523"
FT VARIANT 326
FT /note="G -> V (in PKD4; dbSNP:rs778329699)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018524"
FT VARIANT 372
FT /note="F -> L (in PKD4; dbSNP:rs1582038191)"
FT /evidence="ECO:0000269|PubMed:16677362"
FT /id="VAR_027439"
FT VARIANT 387
FT /note="Missing (in PKD4; dbSNP:rs1554218506)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018525"
FT VARIANT 457
FT /note="E -> D"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018526"
FT VARIANT 466
FT /note="G -> E (in PKD4; dbSNP:rs750730042)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066421"
FT VARIANT 470
FT /note="G -> V (in PKD4; dbSNP:rs776845008)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066422"
FT VARIANT 473
FT /note="I -> S (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018527"
FT VARIANT 486
FT /note="Y -> H (in PKD4)"
FT /evidence="ECO:0000269|PubMed:15108281"
FT /id="VAR_018528"
FT VARIANT 488
FT /note="R -> P (in dbSNP:rs186202437)"
FT /id="VAR_018529"
FT VARIANT 496..4074
FT /note="Missing (found in a patient affected by polycystic
FT liver disease; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080923"
FT VARIANT 496
FT /note="R -> P (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018530"
FT VARIANT 539
FT /note="I -> T (in PKD4; dbSNP:rs749730748)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066423"
FT VARIANT 579
FT /note="T -> M (in dbSNP:rs45500692)"
FT /evidence="ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:25701400"
FT /id="VAR_018531"
FT VARIANT 656
FT /note="W -> C (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018532"
FT VARIANT 686
FT /note="H -> P (in PKD4)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066424"
FT VARIANT 703
FT /note="D -> N (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018533"
FT VARIANT 723
FT /note="R -> C (in dbSNP:rs794727366)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066425"
FT VARIANT 724
FT /note="P -> R (in PKD4; dbSNP:rs1229139298)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066426"
FT VARIANT 732
FT /note="V -> F (in dbSNP:rs201432731)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018534"
FT VARIANT 739
FT /note="P -> L (in PKD4; dbSNP:rs758352210)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018535"
FT VARIANT 752
FT /note="T -> M (in dbSNP:rs200654041)"
FT /evidence="ECO:0000269|PubMed:11919560"
FT /id="VAR_014042"
FT VARIANT 757
FT /note="I -> L (in PKD4; unknown pathological significance;
FT dbSNP:rs777183511)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018536"
FT VARIANT 760
FT /note="R -> C (in dbSNP:rs9370096)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454"
FT /id="VAR_014043"
FT VARIANT 760
FT /note="R -> H (in PKD4; dbSNP:rs745770404)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014044"
FT VARIANT 760
FT /note="R -> W (in dbSNP:rs9370096)"
FT /id="VAR_051282"
FT VARIANT 805
FT /note="P -> L (in PKD4; dbSNP:rs199531851)"
FT /evidence="ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:15108281"
FT /id="VAR_018537"
FT VARIANT 830
FT /note="N -> S (in dbSNP:rs62406032)"
FT /evidence="ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:25701400"
FT /id="VAR_018538"
FT VARIANT 852
FT /note="W -> R"
FT /evidence="ECO:0000269|PubMed:11919560"
FT /id="VAR_014045"
FT VARIANT 899
FT /note="T -> P (in PKD4; dbSNP:rs922828020)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018539"
FT VARIANT 997
FT /note="M -> K (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018540"
FT VARIANT 1030
FT /note="A -> E (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018541"
FT VARIANT 1081
FT /note="R -> C (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs200986136)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036229"
FT VARIANT 1096
FT /note="L -> R (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036230"
FT VARIANT 1122
FT /note="G -> S (in PKD4)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014046"
FT VARIANT 1123
FT /note="G -> S (in PKD4; dbSNP:rs142107837)"
FT /evidence="ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12874454"
FT /id="VAR_018542"
FT VARIANT 1136
FT /note="Y -> C (in dbSNP:rs41273726)"
FT /id="VAR_018543"
FT VARIANT 1150
FT /note="A -> P"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018544"
FT VARIANT 1204
FT /note="C -> Y"
FT /evidence="ECO:0000269|PubMed:12079288"
FT /id="VAR_014047"
FT VARIANT 1249
FT /note="C -> W (in PKD4; dbSNP:rs748540413)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014048"
FT VARIANT 1262
FT /note="A -> V (in dbSNP:rs9296669)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12846734"
FT /id="VAR_014049"
FT VARIANT 1283
FT /note="S -> L"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018545"
FT VARIANT 1389
FT /note="P -> T (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018546"
FT VARIANT 1407
FT /note="L -> R (in PKD4; dbSNP:rs1464962854)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014050"
FT VARIANT 1472
FT /note="C -> Y (in PKD4)"
FT /evidence="ECO:0000269|PubMed:15108281"
FT /id="VAR_018547"
FT VARIANT 1486
FT /note="P -> L (in PKD4; dbSNP:rs1421520936)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018548"
FT VARIANT 1584
FT /note="S -> I (in PKD4; dbSNP:rs1197981811)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018549"
FT VARIANT 1624
FT /note="R -> W (in PKD4; unknown pathological significance;
FT dbSNP:rs200391019)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:25701400"
FT /id="VAR_014051"
FT VARIANT 1664
FT /note="S -> F (in PKD4; dbSNP:rs28937907)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014052"
FT VARIANT 1709
FT /note="L -> F (in dbSNP:rs45517932)"
FT /evidence="ECO:0000269|PubMed:12846734,
FT ECO:0000269|PubMed:12874454"
FT /id="VAR_018550"
FT VARIANT 1712
FT /note="G -> R (in a patient with polycystic kidney disease;
FT dbSNP:rs141103838)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066427"
FT VARIANT 1741
FT /note="V -> M (in PKD4; dbSNP:rs137852946)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:12846734"
FT /id="VAR_014053"
FT VARIANT 1781
FT /note="T -> I (in PKD4; dbSNP:rs1554197025)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018551"
FT VARIANT 1789
FT /note="V -> L (in PKD4; dbSNP:rs1288521396)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018552"
FT VARIANT 1806
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036231"
FT VARIANT 1817
FT /note="V -> G (in PKD4)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066428"
FT VARIANT 1833
FT /note="S -> L (in PKD4; dbSNP:rs201105958)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018553"
FT VARIANT 1838
FT /note="Y -> C (in PKD4; dbSNP:rs777999875)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018554"
FT VARIANT 1867
FT /note="S -> N (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018555"
FT VARIANT 1870
FT /note="L -> V (in dbSNP:rs2435322)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454"
FT /id="VAR_018556"
FT VARIANT 1875
FT /note="V -> G (in PKD4; dbSNP:rs202016058)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066429"
FT VARIANT 1917
FT /note="Q -> R (in PKD4; dbSNP:rs1412045164)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014054"
FT VARIANT 1928
FT /note="W -> L (in PKD4)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066430"
FT VARIANT 1942
FT /note="D -> G (in PKD4; dbSNP:rs1210846081)"
FT /evidence="ECO:0000269|PubMed:12846734,
FT ECO:0000269|PubMed:12874454"
FT /id="VAR_018557"
FT VARIANT 1971
FT /note="G -> D (in PKD4; dbSNP:rs180675584)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018558"
FT VARIANT 1995
FT /note="E -> G (in PKD4; dbSNP:rs1554144359)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014055"
FT VARIANT 1998
FT /note="I -> T (in PKD4; dbSNP:rs1210348558)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018559"
FT VARIANT 2009
FT /note="A -> T (in PKD4; dbSNP:rs761786260)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066431"
FT VARIANT 2032
FT /note="V -> L (in PKD4; dbSNP:rs1187112770)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018560"
FT VARIANT 2106
FT /note="L -> R (in PKD4; dbSNP:rs1254909885)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066432"
FT VARIANT 2134
FT /note="L -> P (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018561"
FT VARIANT 2210
FT /note="G -> E (in PKD4)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066433"
FT VARIANT 2219
FT /note="S -> L (in PKD4)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066434"
FT VARIANT 2224
FT /note="G -> R (in PKD4; may affect splicing;
FT dbSNP:rs759687904)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066435"
FT VARIANT 2303
FT /note="I -> F (in PKD4; dbSNP:rs751084512)"
FT /evidence="ECO:0000269|PubMed:15108281"
FT /id="VAR_018562"
FT VARIANT 2331
FT /note="I -> K (in PKD4; dbSNP:rs200179145)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014056"
FT VARIANT 2422
FT /note="C -> G (in PKD4; dbSNP:rs201881567)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018563"
FT VARIANT 2422
FT /note="C -> R (in PKD4; dbSNP:rs201881567)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066436"
FT VARIANT 2431
FT /note="E -> V (in PKD4; may affect splicing;
FT dbSNP:rs1280884139)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066437"
FT VARIANT 2436
FT /note="T -> I (found in a patient affected by polycystic
FT liver disease; unknown pathological significance;
FT dbSNP:rs147851214)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080924"
FT VARIANT 2573
FT /note="R -> C (in PKD4; dbSNP:rs752994816)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066438"
FT VARIANT 2615
FT /note="A -> G"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018564"
FT VARIANT 2641
FT /note="T -> A (in dbSNP:rs7766366)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018565"
FT VARIANT 2648
FT /note="G -> S (found in a patient affected by polycystic
FT liver disease; unknown pathological significance;
FT dbSNP:rs139555370)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080925"
FT VARIANT 2661
FT /note="Y -> H (in a patient with polycystic kidney
FT disease)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066439"
FT VARIANT 2688
FT /note="C -> F (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018566"
FT VARIANT 2761
FT /note="D -> Y (in PKD4; dbSNP:rs1554263080)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018567"
FT VARIANT 2772
FT /note="L -> P (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018568"
FT VARIANT 2798
FT /note="V -> G (in PKD4; dbSNP:rs1554243589)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066440"
FT VARIANT 2803
FT /note="C -> R (in PKD4; dbSNP:rs398124495)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066441"
FT VARIANT 2804
FT /note="M -> K (in PKD4; dbSNP:rs794727759)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066442"
FT VARIANT 2861
FT /note="S -> G (in dbSNP:rs150925674)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018569"
FT VARIANT 2863
FT /note="Y -> C (in PKD4; dbSNP:rs1342555536)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018570"
FT VARIANT 2869
FT /note="T -> K (in dbSNP:rs142522748)"
FT /evidence="ECO:0000269|PubMed:12846734,
FT ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281,
FT ECO:0000269|PubMed:25701400"
FT /id="VAR_018571"
FT VARIANT 2938
FT /note="T -> M (in dbSNP:rs776068047)"
FT /evidence="ECO:0000269|PubMed:11919560"
FT /id="VAR_014057"
FT VARIANT 2957
FT /note="I -> T (in PKD4; dbSNP:rs760222236)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454,
FT ECO:0000269|PubMed:15108281, ECO:0000269|PubMed:25701400"
FT /id="VAR_014058"
FT VARIANT 2962
FT /note="D -> G (in PKD4; dbSNP:rs1554220680)"
FT /evidence="ECO:0000269|PubMed:15108281"
FT /id="VAR_018572"
FT VARIANT 2983
FT /note="S -> L (in PKD4; dbSNP:rs141169758)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018573"
FT VARIANT 3018
FT /note="S -> F (in PKD4; dbSNP:rs137852945)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014059"
FT VARIANT 3024
FT /note="C -> Y (found in a patient affected by polycystic
FT liver disease; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080926"
FT VARIANT 3036
FT /note="V -> G (in PKD4; dbSNP:rs893497345)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018574"
FT VARIANT 3049
FT /note="H -> R (in PKD4; dbSNP:rs367678592)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066443"
FT VARIANT 3052
FT /note="D -> Y (in dbSNP:rs765526)"
FT /id="VAR_027440"
FT VARIANT 3070..4074
FT /note="Missing (probable disease-associated variant found
FT in a patient affected by polycystic liver disease)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080927"
FT VARIANT 3072
FT /note="A -> V (in dbSNP:rs139306706)"
FT /id="VAR_018575"
FT VARIANT 3081
FT /note="I -> V (in PKD4; dbSNP:rs142146981)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018576"
FT VARIANT 3088
FT /note="D -> N (in dbSNP:rs201066635)"
FT /id="VAR_018577"
FT VARIANT 3107
FT /note="R -> P"
FT /id="VAR_018578"
FT VARIANT 3124
FT /note="H -> Y (in PKD4; dbSNP:rs1554218666)"
FT /evidence="ECO:0000269|PubMed:12874454,
FT ECO:0000269|PubMed:15108281"
FT /id="VAR_018579"
FT VARIANT 3139
FT /note="D -> Y (in dbSNP:rs45503297)"
FT /evidence="ECO:0000269|PubMed:11898128,
FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454,
FT ECO:0000269|PubMed:15108281"
FT /id="VAR_014060"
FT VARIANT 3143
FT /note="R -> I"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018580"
FT VARIANT 3167
FT /note="I -> L (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018581"
FT VARIANT 3175
FT /note="N -> D (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018582"
FT VARIANT 3175
FT /note="N -> S (in PKD4; dbSNP:rs1343246818)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018583"
FT VARIANT 3177
FT /note="I -> T (in PKD4; dbSNP:rs200511261)"
FT /evidence="ECO:0000269|PubMed:12846734,
FT ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281"
FT /id="VAR_018584"
FT VARIANT 3207
FT /note="A -> T (in PKD4; dbSNP:rs1242089464)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066444"
FT VARIANT 3210
FT /note="S -> C (found in a patient affected by polycystic
FT liver disease; unknown pathological significance;
FT dbSNP:rs141081295)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080928"
FT VARIANT 3219
FT /note="V -> A (in a patient with polycystic kidney
FT disease)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066445"
FT VARIANT 3263
FT /note="V -> A (in dbSNP:rs146519878)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080929"
FT VARIANT 3289
FT /note="S -> I (in PKD4; unknown pathological significance;
FT dbSNP:rs148932323)"
FT /evidence="ECO:0000269|PubMed:25701400"
FT /id="VAR_018585"
FT VARIANT 3293
FT /note="D -> V (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:12874454"
FT /id="VAR_018586"
FT VARIANT 3346
FT /note="C -> R (in PKD4; unknown pathological significance;
FT dbSNP:rs149798764)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018587"
FT VARIANT 3407..4074
FT /note="Missing (found in a patient affected by polycystic
FT liver disease; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080930"
FT VARIANT 3440
FT /note="V -> D (in dbSNP:rs756792624)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018588"
FT VARIANT 3468
FT /note="I -> V (in PKD4; dbSNP:rs748863662)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018589"
FT VARIANT 3471
FT /note="V -> G (in PKD4; dbSNP:rs137852950)"
FT /evidence="ECO:0000269|PubMed:12506140"
FT /id="VAR_018590"
FT VARIANT 3482
FT /note="R -> C (in PKD4; dbSNP:rs148617572)"
FT /evidence="ECO:0000269|PubMed:12506140,
FT ECO:0000269|PubMed:15108281"
FT /id="VAR_018591"
FT VARIANT 3502
FT /note="E -> V (in PKD4; dbSNP:rs1554183496)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018592"
FT VARIANT 3505
FT /note="S -> R (in dbSNP:rs139014478)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018593"
FT VARIANT 3529
FT /note="E -> Q (in dbSNP:rs145184792)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018594"
FT VARIANT 3551
FT /note="E -> K (in dbSNP:rs751593192)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018595"
FT VARIANT 3553
FT /note="I -> T (in PKD4; dbSNP:rs137852948)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12506140"
FT /id="VAR_014061"
FT VARIANT 3622
FT /note="C -> Y (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12846734"
FT /id="VAR_018596"
FT VARIANT 3780
FT /note="P -> S (found in a patient affected by polycystic
FT liver disease; unknown pathological significance;
FT dbSNP:rs41273722)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080931"
FT VARIANT 3783
FT /note="P -> S (in PKD4)"
FT /evidence="ECO:0000269|PubMed:12874454"
FT /id="VAR_018597"
FT VARIANT 3837
FT /note="V -> I (in dbSNP:rs9474034)"
FT /id="VAR_027441"
FT VARIANT 3842
FT /note="R -> L (in dbSNP:rs76572975)"
FT /id="VAR_018598"
FT VARIANT 3899
FT /note="Q -> R (in dbSNP:rs4715227)"
FT /evidence="ECO:0000269|PubMed:12846734,
FT ECO:0000269|PubMed:12874454"
FT /id="VAR_018599"
FT VARIANT 3905
FT /note="I -> N (in dbSNP:rs2661488)"
FT /id="VAR_027442"
FT VARIANT 3913
FT /note="R -> H (in dbSNP:rs2661487)"
FT /id="VAR_027443"
FT VARIANT 3957
FT /note="R -> C (in PKD4; dbSNP:rs146680689)"
FT /evidence="ECO:0000269|PubMed:19914852"
FT /id="VAR_066446"
FT VARIANT 3960
FT /note="V -> I (in dbSNP:rs34548196)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454"
FT /id="VAR_014062"
FT VARIANT 4009..4074
FT /note="Missing (found in a patient affected by polycystic
FT liver disease; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080932"
FT VARIANT 4037
FT /note="L -> P (found in a patient affected by polycystic
FT liver disease; unknown pathological significance;
FT dbSNP:rs199900211)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080933"
FT VARIANT 4048..4074
FT /note="Missing (found in a patient affected by polycystic
FT liver disease; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080934"
FT VARIANT 4048
FT /note="Q -> R (in dbSNP:rs9381994)"
FT /evidence="ECO:0000269|PubMed:11919560,
FT ECO:0000269|PubMed:12846734"
FT /id="VAR_014063"
FT MUTAGEN 3617..3618
FT /note="KR->AA: Loss of protein convertase cleavage into a
FT 85 kDa PTM fragment."
FT /evidence="ECO:0000269|PubMed:17470460"
SQ SEQUENCE 4074 AA; 446702 MW; 719AA72F1203EDE1 CRC64;
MTAWLISLMS IEVLLLAVRH LSLHIEPEEG SLAGGTWITV IFDGLELGVL YPNNGSQLEI
HLVNVNMVVP ALRSVPCDVF PVFLDLPVVT CRTRSVLSEA HEGLYFLEAY FGGQLVSSPN
PGPRDSCTFK FSKAQTPIVH QVYPPSGVPG KLIHVYGWII TGRLETFDFD AEYIDSPVIL
EAQGDKWVTP CSLINRQMGS CYPIQEDHGL GTLQCHVEGD YIGSQNVSFS VFNKGKSMVH
KKAWLISAKQ DLFLYQTHSE ILSVFPETGS LGGRTNITIT GDFFDNSAQV TIAGIPCDIR
HVSPRKIECT TRAPGKDVRL TTPQPGNRGL LFEVGDAVEG LELTEATPGY RWQIVPNASS
PFGFWSQEGQ PFRARLSGFF VAPETNNYTF WIQADSQASL HFSWSEEPRT KVKVASISVG
TADWFDSWEQ NRDEGTWQQK TPKLELLGGA MYYLEAEHHG IAPSRGMRIG VQIHNTWLNP
DVVTTYLREK HQIRVRAQRL PEVQVLNVSG RGNFFLTWDN VSSQPIPANA TAHLIQTTIE
ELLAVKCKLE PLWSNILLRL GFERGPEVSN SDGDLTSGTE PFCGRFSLRQ PRHLVLTPPA
AQKGYRLDQY THLCLAYKGH MNKILKMIVS FTIGFQNMVK NTTCDWSLTR TSPESWQFDC
TDLWETCVRC FGDLQPPPAN SPVLVHQINL LPLAQETGLF YVDEIIIADT NVTVSQADSG
TARPGGNLVE SVSVVGSPPV YSVTSWLAGC GTELPLITAR SVPTEGTEEG SGLVLVTTQR
RQRTSPPLGG HFRIQLPNTV ISDVPVQISA HHLHQLLQNN ADDFTSRYLN ASDFTVKEDL
YTCYEHVWTL SWSTQIGDLP NFIRVSDENL TGVNPAAATR VVYDGGVFLG PIFGDMLATA
NQHTQVVVRV NDVPAHCPGS CSFQYLQGST PCVHSVWYSI DGDINLMIYI TGTGFSGDSQ
FLQVTVNKTS CKVIFSNQTN VVCQTDLLPV GMHRILMLVR PSGLAISATG EDLFLNVKPR
LDMVEPSRAA DIGGLWATIR GSSLEGVSLI LFGSYSCAIN VATSNSSRIQ CKVPPRGKDG
RIVNVTVIRG DYSAVLPRAF TYVSSLNPVI VTLSRNISNI AGGETLVIGV ARLMNYTDLD
VEVHVQDALA PVHTQSAWGL EVALPPLPAG LHRISVSING VSIHSQGVDL HIQYLTEVFS
IEPCCGSLLG GTILSISGIG FSRDPALVWV LVGNRSCDIV NLTEASIWCE TLPAPQIPDA
GAPTVPAAVE VWAGNRFFAR GPSPSLVGKG FTFMYEAAAT PVVTAMQGEI TNSSLSLHVG
GSNLSNSVIL LGNLNCDVET QSFQGNVSLS GCSIPLHSLE AGIYPLQVRQ KQMGFANMSV
VLQQFAVMPR IMAIFPSQGS ACGGTILTVR GLLLNSRRRS VRVDLSGPFT CVILSLGDHT
ILCQVSLEGD PLPGASFSLN VTVLVNGLTS ECQGNCTLFI REEASPVMDA LSTNTSGSLT
TVLIRGQRLA TTADEPMVFV DDQLPCNVTF FNASHVVCQT RDLAPGPHYL SVFYTRNGYA
CSGNVSRHFY IMPQVFHYFP KNFSLHGGSL LTIEGTGLRG QNTTSVYIDQ QTCLTVNIGA
ELIRCIVPTG NGSVALEIEV DGLWYHIGVI GYNKAFTPEL ISISQSDDIL TFAVAQISGA
ANIDIFIGMS PCVGVSGNHT VLQCVVPSLP AGEYHVRGYD CIRGWASSAL VFTSRVIITA
VTENFGCLGG RLVHVFGAGF SPGNVSAAVC GAPCRVLANA TVSAFSCLVL PLDVSLAFLC
GLKREEDSCE AARHTYVQCD LTVAMATEQL LESWPYLYIC EESSQCLFVP DHWAESMFPS
FSGLFISPKL ERDEVLIYNS SCNITMETEA EMECETPNQP ITVKITEIRK RWGQNTQGNF
SLQFCRRWSR THSWFPERLP QDGDNVTVEN GQLLLLDTNT SILNLLHIKG GKLIFMAPGP
IELRAHAILV SDGGELRIGS EDKPFQGRAQ ITLYGSSYST PFFPYGVKFL AVRNGTLSLH
GSLPEVIVTC LRATAHALDT VLALEDAVDW NPGDEVVIIS GTGVKGAKPM EEIVTVETVQ
DTDLYLKSPL RYSHNFTENW VAGEHHILKA TVALLSRSIT IQGNLTNERE KLLVSCQEAN
APEGNLQHCL YSMSEKMLGS RDMGARVIVQ SFPEEPSQVQ LKGVQFQVLG QAFHKHLSSL
TLVGAMRESF IQGCTVRNSF SRGLSMCGTL GLKVDSNVFY NILGHALLVG TCTEMRYISW
EAIHGRKDDW SGHGNIIRNN VIIQVSGAEG LSNPEMLTPS GIYICSPTNV IEGNRVCGAG
YGYFFHLMTN QTSQAPLLSF TQNIAHSCTR YGLFVYPKFQ PPWDNVTGTT LFQSFTVWES
AGGAQIFRSS NLRLKNFKVY SCRDFGIDVL ESDANTSVTD SLLLGHFAHK GSLCMSSGIK
TPKRWELMVS NTTFVNFDLI NCVAIRTCSD CSQGQGGFTV KTSQLKFTNS SNLVAFPFPH
AAILEDLDGS LSGKNRSHIL ASMETLSASC LVNSSFGRVV HGSACGGGVL FHRMSIGLAN
TPEVSYDLTM TDSRNKTTTV NYVRDTLSNP RGWMALLLDQ ETYSLQSENL WINRSLQYSA
TFDNFAPGNY LLLVHTDLPP YPDILLRCGS RVGLSFPFLP SPGQNQGCDW FFNSQLRQLT
YLVSGEGQVQ VILRVKEGMP PTISASTSAP ESALKWSLPE TWQGVEEGWG GYNNTIPGPG
DDVLILPNRT VLVDTDLPFF KGLYVMGTLD FPVDRSNVLS VACMVIAGGE LKVGTLENPL
EKEQKLLILL RASEGVFCDR MNGIHIDPGT IGVYGKVHLY SAYPKNSWTH LGADIASGNE
RIIVEDAVDW RPHDKIVLSS SSYEPHEAEV LTVKEVKGHH VRIYERLKHR HIGSVHVTED
GRHIRLAAEV GLLTRNIQIQ PDVSCRGRLF VGSFRKSSRE EFSGVLQLLN VEIQNFGSPL
YSSVEFSNVS AGSWIISSTL HQSCGGGIHA AASHGVLLND NIVFGTAGHG IDLEGQAYTV
TNNLVVLMTQ PAWSTIWVAG IKVNQVKDIN LHGNVVAGSE RLGFHIRGHK CSSCELLWSD
NVAHSSLHGL HLYKESGLDN CTRISGFLAF KNFDYGAMLH VENSVEIENI TLVDNTIGLL
AVVYVFSAPQ NSVKKVQIVL RNSVIVATSS SFDCIQDKVK PHSANLTSTD RAPSNPRGGR
IGILWPVFTS EPNQWPQEPW HKVRNDHSIS GIMKLQDVTF SSFVKSCYSD DLDVCILPNA
ENSGIMHPIT AERTRMLKIK DKNKFYFPSL QPRKDLGKVV CPELDCASPR KYLFKDLDGR
ALGLPPPVSV FPKTEAEWTA SFFNAGTFRE EQKCTYQFLM QGFICKQTDQ VVLILDSADA
IWAIQKLYPV VSVTSGFVDV FSSVNANIPC STSGSVSTFY SILPIRQITK VCFMDQTPQV
LRFFLLGNKS TSKLLLAVFY HELQSPHVFL GESFIPPTLV QSASLLLNES IGANYFNIMD
NLLYVVLQGE EPIEIRSGVS IHLALTVMVS VLEKGWEIVI LERLTNFLQI GQNQIRFIHE
MPGHEETLKA IADSRAKRKR NCPTVTCTSH YRRVGQRRPL MMEMNSHRAS PPMTVETISK
VIVIEIGDSP TVRSTGMISS LSSNKLQNLA HRVITAQQTG VLENVLNMTI GALLVTQSKG
VIGYGNTSSF KTGNLIYIRP YALSILVQPS DGEVGNELPV QPQLVFLDEQ NRRVESLGPP
SEPWTISASL EGASDSVLKG CTQAETQDGY VSFYNLAVLI SGSNWHFIFT VTSPPGVNFT
ARSKPFAVLP VTRKEKSTII LAASLSSVAS WLALSCLVCC WLKRSKSRKT KPEEIPESQT
NNQNIHIHIS SKRRESQGPK KEDTVVGEDM RMKVMLGKVN QCPHQLMNGV SRRKVSRHIV
REEEAAVPAP GTTGITSHGH ICAPGAPAQQ VYLQETGNWK EGQEQLLRYQ LAGQNQLLLL
CPDFRQERQQ LPGQSRLSKQ SGSLGLSQEK KASCGATEAF CLHSVHPETI QEQL
