PRPH2_HUMAN
ID PRPH2_HUMAN Reviewed; 346 AA.
AC P23942; Q5TFH5; Q6DK65;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Peripherin-2;
DE AltName: Full=Retinal degeneration slow protein;
DE AltName: Full=Tetraspanin-22;
DE Short=Tspan-22;
GN Name=PRPH2; Synonyms=PRPH, RDS, TSPAN22;
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].
RX PubMed=1679750; DOI=10.1016/0888-7543(91)90457-p;
RA Travis G.H., Christerson L., Danielson P.E., Klisak I., Sparkes R.S.,
RA Hahn L.B., Dryja T.P., Sutcliffe G.J.;
RT "The human retinal degeneration slow (RDS) gene: chromosome assignment and
RT structure of the mRNA.";
RL Genomics 10:733-739(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kajiwara K.;
RL Submitted (FEB-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS GLN-304;
RP ARG-310 AND ASP-338.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP REVIEW ON VARIANTS.
RX PubMed=8956033;
RX DOI=10.1002/(sici)1098-1004(1996)8:4<297::aid-humu1>3.0.co;2-5;
RA Keen T.J., Inglehearn C.F.;
RT "Mutations and polymorphisms in the human peripherin-RDS gene and their
RT involvement in inherited retinal degeneration.";
RL Hum. Mutat. 8:297-303(1996).
RN [6]
RP VARIANT RP7 CYS-118 DEL.
RX PubMed=1749427; DOI=10.1038/354478a0;
RA Farrar G.J., Kenna P., Jordan S.A., Kumar-Singh R., Humphries M.M.,
RA Sharp E.M., Sheils D.M., Humphries P.;
RT "A three-base-pair deletion in the peripherin-RDS gene in one form of
RT retinitis pigmentosa.";
RL Nature 354:478-480(1991).
RN [7]
RP VARIANTS RP7 PRO-185; LEU-216 AND PRO-219 DEL.
RX PubMed=1684223; DOI=10.1038/354480a0;
RA Kajiwara K., Hahn L.B., Mukai S., Travis G.H., Berson E.L., Dryja T.P.;
RT "Mutations in the human retinal degeneration slow gene in autosomal
RT dominant retinitis pigmentosa.";
RL Nature 354:480-483(1991).
RN [8]
RP VARIANT RP7 GLY-212.
RX PubMed=1427912; DOI=10.1016/s0888-7543(05)80193-4;
RA Farrar G.J., Kenna P., Jordan S.A., Kumar-Singh R., Humphries M.M.,
RA Sharp E.M., Sheils D.M., Humphries P.;
RT "Autosomal dominant retinitis pigmentosa: a novel mutation at the
RT peripherin/RDS locus in the original 6p-linked pedigree.";
RL Genomics 14:805-807(1992).
RN [9]
RP ERRATUM OF PUBMED:1427912.
RX PubMed=8449524;
RA Farrar G.J., Kenna P., Jordan S.A., Kumar-Singh R., Humphries M.M.,
RA Sharp E.M., Sheils D.M., Humphries P.;
RL Genomics 15:466-466(1993).
RN [10]
RP VARIANT MDPT1 ASP-167.
RX PubMed=8485574; DOI=10.1038/ng0393-202;
RA Nichols B.E., Sheffield V.C., Vandenburgh K., Drack A.V., Kimura A.E.,
RA Stone E.M.;
RT "Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation
RT in codon 167 of the RDS gene.";
RL Nat. Genet. 3:202-207(1993).
RN [11]
RP VARIANTS GLN-172 AND TRP-172.
RX PubMed=8485576; DOI=10.1038/ng0393-213;
RA Wells J., Wroblewski J., Keen J., Inglehearn C., Jubb C., Eckstein A.,
RA Jay M., Arden G., Bhattacharya S., Fitzke F.;
RT "Mutations in the human retinal degeneration slow (RDS) gene can cause
RT either retinitis pigmentosa or macular dystrophy.";
RL Nat. Genet. 3:213-218(1993).
RN [12]
RP VARIANT FOVEOMACULAR DYSTROPHY ARG-210.
RX PubMed=7519821; DOI=10.1016/s0002-9394(14)72913-7;
RA Feist R.M., White M.F. Jr., Skalka H., Stone E.M.;
RT "Choroidal neovascularization in a patient with adult foveomacular
RT dystrophy and a mutation in the retinal degeneration slow gene (Pro 210
RT Arg).";
RL Am. J. Ophthalmol. 118:259-260(1994).
RN [13]
RP VARIANT RP7 LYS-244.
RX PubMed=8020945; DOI=10.1006/geno.1994.1142;
RA Kikawa E., Nakazawa M., Chida Y., Shiono T., Tamai M.;
RT "A novel mutation (Asn244Lys) in the peripherin/RDS gene causing autosomal
RT dominant retinitis pigmentosa associated with bull's-eye maculopathy
RT detected by nonradioisotopic SSCP.";
RL Genomics 20:137-139(1994).
RN [14]
RP VARIANT TRP-172.
RX PubMed=7493155; DOI=10.3109/13816819509056911;
RA Reig C., Serra A., Gean E., Vidal M., Arumi J., De la Calzada M.D.,
RA Antich J., Carballo M.;
RT "A point mutation in the RDS-peripherin gene in a Spanish family with
RT central areolar choroidal dystrophy.";
RL Ophthalmic Genet. 16:39-44(1995).
RN [15]
RP ERRATUM OF PUBMED:7493155.
RA Reig C., Serra A., Gean E., Vidal M., Arumi J., De la Calzada M.D.,
RA Antich J., Carballo M.;
RL Ophthalmic Genet. 16:179-179(1995).
RN [16]
RP VARIANT RP7 ARG-210.
RX PubMed=7862413; DOI=10.1016/s0161-6420(95)31029-9;
RA Gorin M.B., Jackson K.E., Ferrell R.E., Sheffield V.C., Jacobson S.G.,
RA Gass J.D., Mitchell E., Stone E.M.;
RT "A peripherin/retinal degeneration slow mutation (Pro-210-Arg) associated
RT with macular and peripheral retinal degeneration.";
RL Ophthalmology 102:246-255(1995).
RN [17]
RP VARIANTS VMD3 THR-212; ILE-268 AND ASP-305.
RX PubMed=9338584;
RX DOI=10.1002/(sici)1098-1004(1997)10:4<301::aid-humu6>3.0.co;2-j;
RA Felbor U., Schilling H., Weber B.H.F.;
RT "Adult vitelliform macular dystrophy is frequently associated with
RT mutations in the peripherin/RDS gene.";
RL Hum. Mutat. 10:301-309(1997).
RN [18]
RP VARIANTS MDPT1 ARG-210; ARG-213 AND TRP-220, AND VARIANTS MACULAR DYSTROPHY
RP TRP-172 AND ARG-219.
RX PubMed=9443872; DOI=10.1086/301679;
RA Payne A.M., Downes S.M., Bessant D.A.R., Bird A.C., Bhattacharya S.S.;
RT "Founder effect, seen in the British population, of the 172 peripherin/RDS
RT mutation- and further refinement of genetic positioning of the
RT peripherin/RDS gene.";
RL Am. J. Hum. Genet. 62:192-195(1998).
RN [19]
RP VARIANT LEU-313.
RA Ruiz A., Borrego S., Sanchez J., Antinolo G.;
RT "P313L: a novel amino acid substitution within the C-terminal domain of the
RT human RDS/peripherin gene.";
RL Hum. Mutat. 11:415-416(1998).
RN [20]
RP VARIANT RP7 ASP-208.
RX PubMed=10627133;
RX DOI=10.1002/(sici)1098-1004(1998)12:1<70::aid-humu13>3.0.co;2-g;
RA Trujillo M.J., Bueno J., Osorio A., Sanz R., Garcia-Sandoval B., Ramos C.,
RA Ayuso C.;
RT "Three novel RDS-peripherin mutations (689delT, 857del17, G208D) in Spanish
RT families affected with autosomal dominant retinal degenerations.";
RL Hum. Mutat. 12:70-70(1998).
RN [21]
RP VARIANT RP7 LEU-210, AND VARIANTS GLN-304 AND ASP-338.
RX PubMed=11485765; DOI=10.1016/s0021-5155(01)00334-3;
RA Budu M.M., Hayasaka S., Yamada T., Zhang X.Y., Hayasaka Y.;
RT "Peripherin/RDS gene mutation (Pro210Leu) and polymorphisms in Japanese
RT patients with retinal dystrophies.";
RL Jpn. J. Ophthalmol. 45:355-358(2001).
RN [22]
RP VARIANT MACULAR DYSTROPHY ASN-169 DEL.
RX PubMed=14557182; DOI=10.1001/archopht.121.10.1452;
RA van Lith-Verhoeven J.J., van den Helm B., Deutman A.F., Bergen A.A.,
RA Cremers F.P., Hoyng C.B., de Jong P.T.;
RT "A peculiar autosomal dominant macular dystrophy caused by an asparagine
RT deletion at codon 169 in the peripherin/RDS gene.";
RL Arch. Ophthalmol. 121:1452-1457(2003).
RN [23]
RP VARIANT VMD3 CYS-141.
RX PubMed=15370544; DOI=10.1080/13816810490514388;
RA Yang Z., Li Y., Jiang L., Karan G., Moshfeghi D., O'Connor S., Li X.,
RA Yu Z., Lewis H., Zack D., Jacobson S., Zhang K.;
RT "A novel RDS/peripherin gene mutation associated with diverse macular
RT phenotypes.";
RL Ophthalmic Genet. 25:133-145(2004).
RN [24]
RP VARIANT MDPT1 SER-167.
RX PubMed=16024869; DOI=10.1136/bjo.2004.064188;
RA Testa F., Marini V., Rossi S., Interlandi E., Nesti A., Rinaldi M.,
RA Varano M., Garre C., Simonelli F.;
RT "A novel mutation in the RDS gene in an Italian family with pattern
RT dystrophy.";
RL Br. J. Ophthalmol. 89:1066-1068(2005).
RN [25]
RP VARIANT CACD2 LEU-195.
RX PubMed=16832026; DOI=10.1001/archopht.124.7.1020;
RA Keilhauer C.N., Meigen T., Weber B.H.;
RT "Clinical findings in a multigeneration family with autosomal dominant
RT central areolar choroidal dystrophy associated with an Arg195Leu mutation
RT in the peripherin/RDS gene.";
RL Arch. Ophthalmol. 124:1020-1027(2006).
RN [26]
RP VARIANT SER-137, AND VARIANTS RP7 CYS-141; ARG-198 AND ARG-216.
RX PubMed=16799052; DOI=10.1167/iovs.05-1443;
RA Sullivan L.S., Bowne S.J., Birch D.G., Hughbanks-Wheaton D.,
RA Heckenlively J.R., Lewis R.A., Garcia C.A., Ruiz R.S., Blanton S.H.,
RA Northrup H., Gire A.I., Seaman R., Duzkale H., Spellicy C.J., Zhu J.,
RA Shankar S.P., Daiger S.P.;
RT "Prevalence of disease-causing mutations in families with autosomal
RT dominant retinitis pigmentosa: a screen of known genes in 200 families.";
RL Invest. Ophthalmol. Vis. Sci. 47:3052-3064(2006).
RN [27]
RP VARIANTS VMD3 PHE-213 AND 237-ASP--THR-240 DEL.
RX PubMed=17653047;
RA Gamundi M.J., Hernan I., Muntanyola M., Trujillo M.J., Garcia-Sandoval B.,
RA Ayuso C., Baiget M., Carballo M.;
RT "High prevalence of mutations in peripherin/RDS in autosomal dominant
RT macular dystrophies in a Spanish population.";
RL Mol. Vis. 13:1031-1037(2007).
RN [28]
RP VARIANTS CACD2 TRP-123 AND LEU-221, AND VARIANTS RP7 PRO-126; ALA-216 AND
RP SER-249.
RX PubMed=19038374; DOI=10.1016/j.ajo.2008.09.007;
RA Renner A.B., Fiebig B.S., Weber B.H., Wissinger B., Andreasson S., Gal A.,
RA Cropp E., Kohl S., Kellner U.;
RT "Phenotypic variability and long-term follow-up of patients with known and
RT novel PRPH2/RDS gene mutations.";
RL Am. J. Ophthalmol. 147:518-530(2009).
RN [29]
RP VARIANTS VMD3 PHE-45 AND ILE-209, AND VARIANT CACD2 LEU-195.
RX PubMed=20213611; DOI=10.1177/112067211002000413;
RA Coco R.M., Telleria J.J., Sanabria M.R., Rodriguez-Rua E., Garcia M.T.;
RT "PRPH2 (Peripherin/RDS) mutations associated with different macular
RT dystrophies in a Spanish population: a new mutation.";
RL Eur. J. Ophthalmol. 20:724-732(2010).
RN [30]
RP VARIANT MACULAR DYSTROPHY TRP-172.
RX PubMed=20335603; DOI=10.1167/iovs.09-4655;
RA Poloschek C.M., Bach M., Lagreze W.A., Glaus E., Lemke J.R., Berger W.,
RA Neidhardt J.;
RT "ABCA4 and ROM1: implications for modification of the PRPH2-associated
RT macular dystrophy phenotype.";
RL Invest. Ophthalmol. Vis. Sci. 51:4253-4265(2010).
RN [31]
RP VARIANT RP7 TRP-142.
RX PubMed=22334370; DOI=10.1002/humu.22045;
RA Neveling K., Collin R.W., Gilissen C., van Huet R.A., Visser L.,
RA Kwint M.P., Gijsen S.J., Zonneveld M.N., Wieskamp N., de Ligt J.,
RA Siemiatkowska A.M., Hoefsloot L.H., Buckley M.F., Kellner U., Branham K.E.,
RA den Hollander A.I., Hoischen A., Hoyng C., Klevering B.J.,
RA van den Born L.I., Veltman J.A., Cremers F.P., Scheffer H.;
RT "Next-generation genetic testing for retinitis pigmentosa.";
RL Hum. Mutat. 33:963-972(2012).
RN [32]
RP CHARACTERIZATION OF VARIANTS RP7 ARG-198; LEU-210; SER-214 AND SER-249,
RP CHARACTERIZATION OF VARIANT CACD2 LEU-195, CHARACTERIZATION OF VARIANT VMD3
RP ILE-209, AND CHARACTERIZATION OF VARIANT MDPT1 GLN-220.
RX PubMed=26796962; DOI=10.1371/journal.pgen.1005811;
RA Becirovic E., Boehm S., Nguyen O.N., Riedmayr L.M., Koch M.A., Schulze E.,
RA Kohl S., Borsch O., Santos-Ferreira T., Ader M., Michalakis S., Biel M.;
RT "In vivo analysis of disease-associated point mutations unveils profound
RT differences in mRNA splicing of peripherin-2 in rod and cone
RT photoreceptors.";
RL PLoS Genet. 12:E1005811-E1005811(2016).
CC -!- FUNCTION: Essential for retina photoreceptor outer segment disk
CC morphogenesis, may also play a role with ROM1 in the maintenance of
CC outer segment disk structure (By similarity). Required for the
CC maintenance of retinal outer nuclear layer thickness (By similarity).
CC Required for the correct development and organization of the
CC photoreceptor inner segment (By similarity).
CC {ECO:0000250|UniProtKB:P15499}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Forms a
CC homotetramer (By similarity). Forms a heterotetramer with ROM1 (By
CC similarity). Homotetramer and heterotetramer core complexes go on to
CC form higher order complexes by formation of intermolecular disulfide
CC bonds (By similarity). Interacts with MREG (By similarity). Interacts
CC with STX3 (By similarity). Interacts with SNAP25 (By similarity).
CC {ECO:0000250|UniProtKB:P15499, ECO:0000250|UniProtKB:P17810}.
CC -!- INTERACTION:
CC P23942; P06307: CCK; NbExp=3; IntAct=EBI-25836834, EBI-6624398;
CC P23942; P13473-2: LAMP2; NbExp=3; IntAct=EBI-25836834, EBI-21591415;
CC P23942; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-25836834, EBI-5280197;
CC P23942; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-25836834, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P17810}; Multi-
CC pass membrane protein {ECO:0000255}. Cell projection, cilium,
CC photoreceptor outer segment {ECO:0000250|UniProtKB:P15499}.
CC Photoreceptor inner segment {ECO:0000250|UniProtKB:P15499}.
CC -!- TISSUE SPECIFICITY: Retina (photoreceptor). In rim region of ROS (rod
CC outer segment) disks.
CC -!- DISEASE: Retinitis pigmentosa 7 (RP7) [MIM:608133]: A retinal dystrophy
CC belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:10627133,
CC ECO:0000269|PubMed:11485765, ECO:0000269|PubMed:1427912,
CC ECO:0000269|PubMed:16799052, ECO:0000269|PubMed:1684223,
CC ECO:0000269|PubMed:1749427, ECO:0000269|PubMed:19038374,
CC ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:26796962,
CC ECO:0000269|PubMed:7862413, ECO:0000269|PubMed:8020945}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Retinitis punctata albescens (RPA) [MIM:136880]: A form of
CC fleck retina disease characterized by aggregation of white flecks
CC posteriorly in the retina, causing night blindness and delayed dark
CC adaptation. It differs from fundus albipunctatus in being progressive
CC and evolving to generalized atrophy of the retina. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Macular dystrophy, vitelliform, 3 (VMD3) [MIM:608161]: A form
CC of vitelliform macular dystrophy, a retinal disease characterized by
CC yellow, lipofuscin-containing deposits, usually localized at the center
CC of the macula. Patients usually become symptomatic in the fourth or
CC fifth decade of life with a protracted disease of decreased visual
CC acuity. {ECO:0000269|PubMed:15370544, ECO:0000269|PubMed:17653047,
CC ECO:0000269|PubMed:20213611, ECO:0000269|PubMed:26796962,
CC ECO:0000269|PubMed:9338584}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Macular dystrophy, patterned, 1 (MDPT1) [MIM:169150]: A form
CC of retinal patterned dystrophy, a heterogeneous group of macular
CC disorders that includes reticular (fishnet-like) dystrophy,
CC macroreticular (spider-shaped) dystrophy and butterfly-shaped pigment
CC dystrophy. {ECO:0000269|PubMed:16024869, ECO:0000269|PubMed:26796962,
CC ECO:0000269|PubMed:8485574, ECO:0000269|PubMed:9443872}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Choroidal dystrophy, central areolar 2 (CACD2) [MIM:613105]: A
CC form of central areolar choroidal dystrophy, a retinal disease that
CC affects the macula and results in a well-demarcated circumscribed area
CC of atrophy of the pigment epithelium and choriocapillaris.
CC {ECO:0000269|PubMed:16832026, ECO:0000269|PubMed:19038374,
CC ECO:0000269|PubMed:20213611, ECO:0000269|PubMed:26796962}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in PRPH2 are found in different retinal diseases
CC including cone-rod dystrophy, retinitis pigmentosa, macular
CC degeneration. The mutations underlying autosomal dominant retinitis
CC pigmentosa and severe macular degeneration are largely missense or
CC small in-frame deletions in a large intradiscal loop between the third
CC and fourth transmembrane domains. In contrast, those associated with
CC the milder pattern phenotypes or with digenic RP are scattered more
CC evenly through the gene and are often nonsense mutations. This
CC observation correlates with the hypothesis that the large loop is an
CC important site of interaction between PRPH2 molecules and other protein
CC components in the disk. {ECO:0000269|PubMed:20335603}.
CC -!- SIMILARITY: Belongs to the PRPH2/ROM1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the RDS gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/rdsmut.htm";
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DR EMBL; M73531; AAA60260.1; -; mRNA.
DR EMBL; U07149; AAA16958.1; -; Genomic_DNA.
DR EMBL; U07147; AAA16958.1; JOINED; Genomic_DNA.
DR EMBL; U07148; AAA16958.1; JOINED; Genomic_DNA.
DR EMBL; AL049843; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074720; AAH74720.1; -; mRNA.
DR CCDS; CCDS4871.1; -.
DR PIR; A40308; A40308.
DR RefSeq; NP_000313.2; NM_000322.4.
DR AlphaFoldDB; P23942; -.
DR BioGRID; 111893; 32.
DR IntAct; P23942; 4.
DR STRING; 9606.ENSP00000230381; -.
DR TCDB; 8.A.40.1.3; the tetraspanin (tetraspanin) family.
DR GlyGen; P23942; 2 sites.
DR iPTMnet; P23942; -.
DR PhosphoSitePlus; P23942; -.
DR BioMuta; PRPH2; -.
DR DMDM; 132212; -.
DR jPOST; P23942; -.
DR MassIVE; P23942; -.
DR PaxDb; P23942; -.
DR PeptideAtlas; P23942; -.
DR PRIDE; P23942; -.
DR ProteomicsDB; 54167; -.
DR Antibodypedia; 30169; 68 antibodies from 19 providers.
DR DNASU; 5961; -.
DR Ensembl; ENST00000230381.7; ENSP00000230381.5; ENSG00000112619.8.
DR GeneID; 5961; -.
DR KEGG; hsa:5961; -.
DR UCSC; uc003osk.4; human.
DR CTD; 5961; -.
DR DisGeNET; 5961; -.
DR GeneCards; PRPH2; -.
DR GeneReviews; PRPH2; -.
DR HGNC; HGNC:9942; PRPH2.
DR HPA; ENSG00000112619; Tissue enriched (retina).
DR MalaCards; PRPH2; -.
DR MIM; 136880; phenotype.
DR MIM; 169150; phenotype.
DR MIM; 179605; gene.
DR MIM; 268000; phenotype.
DR MIM; 608133; phenotype.
DR MIM; 608161; phenotype.
DR MIM; 613105; phenotype.
DR neXtProt; NX_P23942; -.
DR Orphanet; 99000; Adult-onset foveomacular vitelliform dystrophy.
DR Orphanet; 99001; Butterfly-shaped pigment dystrophy.
DR Orphanet; 75377; Central areolar choroidal dystrophy.
DR Orphanet; 1872; Cone rod dystrophy.
DR Orphanet; 227796; Fundus albipunctatus.
DR Orphanet; 99003; Multifocal pattern dystrophy simulating fundus flavimaculatus.
DR Orphanet; 791; Retinitis pigmentosa.
DR Orphanet; 52427; Retinitis punctata albescens.
DR Orphanet; 827; Stargardt disease.
DR PharmGKB; PA34310; -.
DR VEuPathDB; HostDB:ENSG00000112619; -.
DR eggNOG; KOG3882; Eukaryota.
DR HOGENOM; CLU_068903_0_0_1; -.
DR InParanoid; P23942; -.
DR OrthoDB; 1470436at2759; -.
DR PhylomeDB; P23942; -.
DR TreeFam; TF331684; -.
DR PathwayCommons; P23942; -.
DR SignaLink; P23942; -.
DR BioGRID-ORCS; 5961; 25 hits in 1062 CRISPR screens.
DR ChiTaRS; PRPH2; human.
DR GeneWiki; Peripherin_2; -.
DR GenomeRNAi; 5961; -.
DR Pharos; P23942; Tbio.
DR PRO; PR:P23942; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P23942; protein.
DR Bgee; ENSG00000112619; Expressed in quadriceps femoris and 111 other tissues.
DR Genevisible; P23942; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0001917; C:photoreceptor inner segment; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:UniProtKB-SubCell.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IEA:Ensembl.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IEA:Ensembl.
DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
DR GO; GO:0009645; P:response to low light intensity stimulus; IEA:Ensembl.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR CDD; cd03162; peripherin_like_LEL; 1.
DR Gene3D; 1.10.1450.10; -; 1.
DR InterPro; IPR000830; Peripherin/rom-1.
DR InterPro; IPR018498; Peripherin/rom-1_CS.
DR InterPro; IPR042026; Peripherin_LEL.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR008952; Tetraspanin_EC2_sf.
DR PANTHER; PTHR19282; PTHR19282; 1.
DR Pfam; PF00335; Tetraspanin; 1.
DR PRINTS; PR00218; PERIPHERNRDS.
DR SUPFAM; SSF48652; SSF48652; 1.
DR PROSITE; PS00930; RDS_ROM1; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell projection; Cone-rod dystrophy; Disease variant;
KW Disulfide bond; Glycoprotein; Membrane; Reference proteome;
KW Retinitis pigmentosa; Sensory transduction; Transmembrane;
KW Transmembrane helix; Vision.
FT CHAIN 1..346
FT /note="Peripherin-2"
FT /id="PRO_0000168105"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..61
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..99
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..264
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 341..346
FT /note="Interaction with MREG"
FT /evidence="ECO:0000250"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 150
FT /note="Interchain (with ROM1)"
FT /evidence="ECO:0000250|UniProtKB:P15499"
FT VARIANT 13
FT /note="R -> W (in RP7; in combination with a null mutation
FT of ROM1; dbSNP:rs61754402)"
FT /id="VAR_006853"
FT VARIANT 32
FT /note="I -> V (in some patients with macular dystrophy;
FT dbSNP:rs61755767)"
FT /id="VAR_006854"
FT VARIANT 45
FT /note="L -> F (in RP7 and VMD3; results in retinitis
FT pigmentosa in combination with a null mutation of ROM1;
FT dbSNP:rs61755770)"
FT /evidence="ECO:0000269|PubMed:20213611"
FT /id="VAR_006855"
FT VARIANT 67
FT /note="Missing (in MDPT1; also in cone-rod dystrophy;
FT dbSNP:rs61755773)"
FT /id="VAR_006856"
FT VARIANT 68
FT /note="G -> R (in MDPT1; also in cone-rod dystrophy;
FT dbSNP:rs61755774)"
FT /id="VAR_006857"
FT VARIANT 118
FT /note="Missing (in RP7)"
FT /evidence="ECO:0000269|PubMed:1749427"
FT /id="VAR_006858"
FT VARIANT 123
FT /note="R -> W (in CACD2; dbSNP:rs563581127)"
FT /evidence="ECO:0000269|PubMed:19038374"
FT /id="VAR_075758"
FT VARIANT 126
FT /note="L -> P (in RP7)"
FT /evidence="ECO:0000269|PubMed:19038374"
FT /id="VAR_075759"
FT VARIANT 126
FT /note="L -> R (in RP7)"
FT /id="VAR_006859"
FT VARIANT 137
FT /note="G -> S (in dbSNP:rs781256236)"
FT /evidence="ECO:0000269|PubMed:16799052"
FT /id="VAR_075760"
FT VARIANT 141
FT /note="Y -> C (in RP7 and VMD3; dbSNP:rs61755781)"
FT /evidence="ECO:0000269|PubMed:15370544,
FT ECO:0000269|PubMed:16799052"
FT /id="VAR_075761"
FT VARIANT 142
FT /note="R -> W (in RP7; also found in a patient with central
FT areolar choroidal dystrophy; dbSNP:rs61755783)"
FT /evidence="ECO:0000269|PubMed:22334370"
FT /id="VAR_006860"
FT VARIANT 153
FT /note="K -> R (in RP7; dbSNP:rs61755785)"
FT /id="VAR_006861"
FT VARIANT 153
FT /note="Missing (in RP7)"
FT /id="VAR_006862"
FT VARIANT 157
FT /note="D -> N (in MDPT1; dbSNP:rs61755787)"
FT /id="VAR_006863"
FT VARIANT 165
FT /note="C -> Y (in RP7; dbSNP:rs61755788)"
FT /id="VAR_006864"
FT VARIANT 167
FT /note="G -> D (in MDPT1; butterfly-shaped;
FT dbSNP:rs61755789)"
FT /evidence="ECO:0000269|PubMed:8485574"
FT /id="VAR_006865"
FT VARIANT 167
FT /note="G -> S (in MDPT1; butterfly-shaped;
FT dbSNP:rs527236098)"
FT /evidence="ECO:0000269|PubMed:16024869"
FT /id="VAR_032052"
FT VARIANT 169
FT /note="Missing (in some patients with macular dystrophy;
FT dbSNP:rs61755790)"
FT /evidence="ECO:0000269|PubMed:14557182"
FT /id="VAR_032053"
FT VARIANT 172
FT /note="R -> G (in MDPT1; butterfly-shaped;
FT dbSNP:rs61755792)"
FT /id="VAR_006866"
FT VARIANT 172
FT /note="R -> Q (in some patients with macular dystrophy;
FT dbSNP:rs61755793)"
FT /evidence="ECO:0000269|PubMed:8485576"
FT /id="VAR_006867"
FT VARIANT 172
FT /note="R -> W (in some patients with macular dystrophy;
FT also in a family affected by central areolar choroidal
FT dystrophy; dbSNP:rs61755792)"
FT /evidence="ECO:0000269|PubMed:7493155,
FT ECO:0000269|PubMed:8485576, ECO:0000269|PubMed:9443872"
FT /id="VAR_006868"
FT VARIANT 173
FT /note="D -> V (in RP7; dbSNP:rs61755794)"
FT /id="VAR_006869"
FT VARIANT 184
FT /note="Y -> S (in cone-rod dystrophy; dbSNP:rs62645926)"
FT /id="VAR_006870"
FT VARIANT 185
FT /note="L -> P (in RP7; digenic inheritance; results in
FT disease in combination with a null mutation of ROM1;
FT dbSNP:rs121918563)"
FT /evidence="ECO:0000269|PubMed:1684223"
FT /id="VAR_006871"
FT VARIANT 193
FT /note="Missing (in MDPT1; also in cone-rod dystrophy;
FT dbSNP:rs62645928)"
FT /id="VAR_006872"
FT VARIANT 195
FT /note="R -> L (in CACD2; increased protein expression;
FT dbSNP:rs121918567)"
FT /evidence="ECO:0000269|PubMed:16832026,
FT ECO:0000269|PubMed:20213611, ECO:0000269|PubMed:26796962"
FT /id="VAR_032054"
FT VARIANT 198
FT /note="S -> R (in RP7; decreased protein expression;
FT dbSNP:rs375978676)"
FT /evidence="ECO:0000269|PubMed:16799052,
FT ECO:0000269|PubMed:26796962"
FT /id="VAR_075762"
FT VARIANT 208
FT /note="G -> D (in RP7; dbSNP:rs139185976)"
FT /evidence="ECO:0000269|PubMed:10627133"
FT /id="VAR_006873"
FT VARIANT 209
FT /note="V -> I (in VMD3; increased protein expression;
FT dbSNP:rs753657349)"
FT /evidence="ECO:0000269|PubMed:20213611,
FT ECO:0000269|PubMed:26796962"
FT /id="VAR_075763"
FT VARIANT 210
FT /note="P -> L (in RP7; decreased protein expression;
FT dbSNP:rs61755798)"
FT /evidence="ECO:0000269|PubMed:11485765,
FT ECO:0000269|PubMed:26796962"
FT /id="VAR_075764"
FT VARIANT 210
FT /note="P -> R (in MDPT1 and RP7; also in adult-onset
FT foveomacular dystrophy with choroidal neovascularization;
FT dbSNP:rs61755798)"
FT /evidence="ECO:0000269|PubMed:7519821,
FT ECO:0000269|PubMed:7862413, ECO:0000269|PubMed:9443872"
FT /id="VAR_006874"
FT VARIANT 210
FT /note="P -> S (in RP7; dbSNP:rs61755797)"
FT /id="VAR_006875"
FT VARIANT 211
FT /note="F -> L (in RP7; dbSNP:rs61755799)"
FT /id="VAR_006876"
FT VARIANT 212
FT /note="S -> G (in RP7; dbSNP:rs61755800)"
FT /evidence="ECO:0000269|PubMed:1427912"
FT /id="VAR_006877"
FT VARIANT 212
FT /note="S -> T (in VMD3; dbSNP:rs61755801)"
FT /evidence="ECO:0000269|PubMed:9338584"
FT /id="VAR_006878"
FT VARIANT 213
FT /note="C -> F (in VMD3)"
FT /evidence="ECO:0000269|PubMed:17653047"
FT /id="VAR_071974"
FT VARIANT 213
FT /note="C -> R (in MDPT1; dbSNP:rs61755802)"
FT /evidence="ECO:0000269|PubMed:9443872"
FT /id="VAR_006879"
FT VARIANT 214
FT /note="C -> S (in RP7; decreased protein expression;
FT dbSNP:rs61755804)"
FT /evidence="ECO:0000269|PubMed:26796962"
FT /id="VAR_006880"
FT VARIANT 216
FT /note="P -> A (in RP7)"
FT /evidence="ECO:0000269|PubMed:19038374"
FT /id="VAR_075765"
FT VARIANT 216
FT /note="P -> L (in RP7; dbSNP:rs61755806)"
FT /evidence="ECO:0000269|PubMed:1684223"
FT /id="VAR_006881"
FT VARIANT 216
FT /note="P -> R (in RP7)"
FT /evidence="ECO:0000269|PubMed:16799052"
FT /id="VAR_075766"
FT VARIANT 216
FT /note="P -> S (in RP7; dbSNP:rs61755805)"
FT /id="VAR_006882"
FT VARIANT 219
FT /note="P -> R (in some patients with macular dystrophy;
FT dbSNP:rs61755808)"
FT /evidence="ECO:0000269|PubMed:9443872"
FT /id="VAR_006883"
FT VARIANT 219
FT /note="Missing (in RP7; dbSNP:rs61755807)"
FT /evidence="ECO:0000269|PubMed:1684223"
FT /id="VAR_006884"
FT VARIANT 220
FT /note="R -> Q (in MDPT1; increased protein expression;
FT dbSNP:rs61755810)"
FT /evidence="ECO:0000269|PubMed:26796962"
FT /id="VAR_006885"
FT VARIANT 220
FT /note="R -> W (in MDPT1; dbSNP:rs61755809)"
FT /evidence="ECO:0000269|PubMed:9443872"
FT /id="VAR_006886"
FT VARIANT 221
FT /note="P -> L (in CACD2)"
FT /evidence="ECO:0000269|PubMed:19038374"
FT /id="VAR_075767"
FT VARIANT 237..240
FT /note="Missing (in VMD3)"
FT /evidence="ECO:0000269|PubMed:17653047"
FT /id="VAR_071975"
FT VARIANT 244
FT /note="N -> H (in cone-rod dystrophy; dbSNP:rs61755815)"
FT /id="VAR_006888"
FT VARIANT 244
FT /note="N -> K (in RP7; with bulls-eye maculopathy;
FT dbSNP:rs61755816)"
FT /evidence="ECO:0000269|PubMed:8020945"
FT /id="VAR_006887"
FT VARIANT 249
FT /note="G -> S (in RP7; decreased protein expression)"
FT /evidence="ECO:0000269|PubMed:19038374,
FT ECO:0000269|PubMed:26796962"
FT /id="VAR_075768"
FT VARIANT 266
FT /note="G -> D (in RP7; dbSNP:rs62645935)"
FT /id="VAR_006889"
FT VARIANT 268
FT /note="V -> I (in VMD3; dbSNP:rs62645936)"
FT /evidence="ECO:0000269|PubMed:9338584"
FT /id="VAR_006890"
FT VARIANT 304
FT /note="E -> Q (associated with D-338 on the same haplotype;
FT dbSNP:rs390659)"
FT /evidence="ECO:0000269|PubMed:11485765,
FT ECO:0000269|PubMed:14574404"
FT /id="VAR_006891"
FT VARIANT 305
FT /note="G -> D (in VMD3; dbSNP:rs61748432)"
FT /evidence="ECO:0000269|PubMed:9338584"
FT /id="VAR_006892"
FT VARIANT 310
FT /note="K -> R (in dbSNP:rs425876)"
FT /evidence="ECO:0000269|PubMed:14574404"
FT /id="VAR_006893"
FT VARIANT 313
FT /note="P -> L (in dbSNP:rs61748434)"
FT /evidence="ECO:0000269|Ref.19"
FT /id="VAR_006894"
FT VARIANT 338
FT /note="G -> D (associated with Q-304 on the same haplotype;
FT dbSNP:rs434102)"
FT /evidence="ECO:0000269|PubMed:11485765,
FT ECO:0000269|PubMed:14574404"
FT /id="VAR_006895"
FT CONFLICT 44
FT /note="E -> G (in Ref. 4; AAH74720)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 39186 MW; 2BB3C5415E194D2A CRC64;
MALLKVKFDQ KKRVKLAQGL WLMNWFSVLA GIIIFSLGLF LKIELRKRSD VMNNSESHFV
PNSLIGMGVL SCVFNSLAGK ICYDALDPAK YARWKPWLKP YLAICVLFNI ILFLVALCCF
LLRGSLENTL GQGLKNGMKY YRDTDTPGRC FMKKTIDMLQ IEFKCCGNNG FRDWFEIQWI
SNRYLDFSSK EVKDRIKSNV DGRYLVDGVP FSCCNPSSPR PCIQYQITNN SAHYSYDHQT
EELNLWVRGC RAALLSYYSS LMNSMGVVTL LIWLFEVTIT IGLRYLQTSL DGVSNPEESE
SESEGWLLEK SVPETWKAFL ESVKKLGKGN QVEAEGAGAG QAPEAG
