BMP15_HUMAN
ID BMP15_HUMAN Reviewed; 392 AA.
AC O95972; Q17RM6; Q5JST1; Q9UMS1;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Bone morphogenetic protein 15;
DE Short=BMP-15;
DE AltName: Full=Growth/differentiation factor 9B;
DE Short=GDF-9B;
DE Flags: Precursor;
GN Name=BMP15; Synonyms=GDF9B;
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 [GENOMIC DNA], AND VARIANT SER-103.
RX PubMed=9849956; DOI=10.1210/mend.12.12.0206;
RA Dube J.L., Wang P., Elvin J., Lyons K.M., Celeste A.J., Matzuk M.M.;
RT "The bone morphogenetic protein 15 gene is X-linked and expressed in
RT oocytes.";
RL Mol. Endocrinol. 12:1809-1817(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10443672; DOI=10.1210/jcem.84.8.5921;
RA Aaltonen J., Laitinen M.P., Vuojolainen K., Jaatinen R.,
RA Horelli-Kuitunen N., Seppae L., Louhio H., Tuuri T., Sjoeberg J.,
RA Buetzow R., Hovatta O., Dale L., Ritvos O.;
RT "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B
RT are expressed in oocytes during early folliculogenesis.";
RL J. Clin. Endocrinol. Metab. 84:2744-2750(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, PYROGLUTAMATE FORMATION AT GLN-268, PHOSPHORYLATION AT SER-273,
RP GLYCOSYLATION AT THR-277, AND HOMODIMERIZATION.
RX PubMed=18227435; DOI=10.1110/ps.073232608;
RA Saito S., Yano K., Sharma S., McMahon H.E., Shimasaki S.;
RT "Characterization of the post-translational modification of recombinant
RT human BMP-15 mature protein.";
RL Protein Sci. 17:362-370(2008).
RN [6]
RP SPECIES-SPECIFIC OVULATION RATE DETERMINATION.
RX PubMed=21970812; DOI=10.1016/j.mce.2011.09.033;
RA Crawford J.L., McNatty K.P.;
RT "The ratio of growth differentiation factor 9: bone morphogenetic protein
RT 15 mRNA expression is tightly co-regulated and differs between species over
RT a wide range of ovulation rates.";
RL Mol. Cell. Endocrinol. 348:339-343(2012).
RN [7]
RP VARIANT ODG2 CYS-235, AND CHARACTERIZATION OF VARIANT ODG2 CYS-235.
RX PubMed=15136966; DOI=10.1086/422103;
RA Di Pasquale E., Beck-Peccoz P., Persani L.;
RT "Hypergonadotropic ovarian failure associated with an inherited mutation of
RT human bone morphogenetic protein-15 (BMP15) gene.";
RL Am. J. Hum. Genet. 75:106-111(2004).
RN [8]
RP VARIANTS POF4 PRO-148 AND THR-180, AND VARIANT LEU-263 INS.
RX PubMed=16645022; DOI=10.1530/eje.1.02135;
RA Laissue P., Christin-Maitre S., Touraine P., Kuttenn F., Ritvos O.,
RA Aittomaki K., Bourcigaux N., Jacquesson L., Bouchard P., Frydman R.,
RA Dewailly D., Reyss A.-C., Jeffery L., Bachelot A., Massin N., Fellous M.,
RA Veitia R.A.;
RT "Mutations and sequence variants in GDF9 and BMP15 in patients with
RT premature ovarian failure.";
RL Eur. J. Endocrinol. 154:739-744(2006).
RN [9]
RP VARIANTS POF4 TRP-61; GLN-61; CYS-76; HIS-76; THR-180; LYS-196; HIS-206;
RP ARG-221 AND VAL-243, AND VARIANTS SER-103; PHE-180 AND LEU-263 INS.
RX PubMed=16508750; DOI=10.1007/s00439-006-0150-0;
RA Dixit H., Rao L.K., Padmalatha V.V., Kanakavalli M., Deenadayal M.,
RA Gupta N., Chakrabarty B., Singh L.;
RT "Missense mutations in the BMP15 gene are associated with ovarian
RT failure.";
RL Hum. Genet. 119:408-415(2006).
RN [10]
RP VARIANTS POF4 TRP-68; THR-180 AND CYS-235, AND VARIANT LEU-263 INS.
RX PubMed=16464940; DOI=10.1210/jc.2005-2650;
RA Di Pasquale E., Rossetti R., Marozzi A., Bodega B., Borgato S., Cavallo L.,
RA Einaudi S., Radetti G., Russo G., Sacco M., Wasniewska M., Cole T.,
RA Beck-Peccoz P., Nelson L.M., Persani L.;
RT "Identification of new variants of human BMP15 gene in a large cohort of
RT women with premature ovarian failure.";
RL J. Clin. Endocrinol. Metab. 91:1976-1979(2006).
RN [11]
RP VARIANTS POF4 TRP-68; HIS-138; PRO-148 AND THR-180, VARIANTS ARG-5 AND
RP LEU-263 INS, CHARACTERIZATION OF VARIANTS POF4 TRP-68; HIS-138; PRO-148 AND
RP THR-180, AND CHARACTERIZATION OF VARIANTS ARG-5 AND LEU-263 INS.
RX PubMed=19263482; DOI=10.1002/humu.20961;
RA Rossetti R., Di Pasquale E., Marozzi A., Bione S., Toniolo D.,
RA Grammatico P., Nelson L.M., Beck-Peccoz P., Persani L.;
RT "BMP15 mutations associated with primary ovarian insufficiency cause a
RT defective production of bioactive protein.";
RL Hum. Mutat. 30:804-810(2009).
RN [12]
RP VARIANT TYR-200, AND VARIANT POF4 CYS-329.
RX PubMed=19438907; DOI=10.1111/j.1365-2265.2009.03613.x;
RA Wang B., Wen Q., Ni F., Zhou S., Wang J., Cao Y., Ma X.;
RT "Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic
RT protein 15 (BMP15) mutation in Chinese women with premature ovarian
RT failure.";
RL Clin. Endocrinol. (Oxf.) 72:135-136(2010).
RN [13]
RP VARIANT TRP-68.
RX PubMed=28585349; DOI=10.1002/humu.23270;
RA Poirier K., Hubert L., Viot G., Rio M., Billuart P., Besmond C.,
RA Bienvenu T.;
RT "CSNK2B splice site mutations in patients cause intellectual disability
RT with or without myoclonic epilepsy.";
RL Hum. Mutat. 38:932-941(2017).
CC -!- FUNCTION: May be involved in follicular development. Oocyte-specific
CC growth/differentiation factor that stimulates folliculogenesis and
CC granulosa cell (GC) growth. {ECO:0000269|PubMed:18227435}.
CC -!- SUBUNIT: Homodimer. But, in contrast to other members of this family,
CC cannot be disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISEASE: Ovarian dysgenesis 2 (ODG2) [MIM:300510]: A disorder
CC characterized by lack of spontaneous pubertal development, primary
CC amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a
CC result of streak gonads. {ECO:0000269|PubMed:15136966}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Premature ovarian failure 4 (POF4) [MIM:300510]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:16464940, ECO:0000269|PubMed:16508750,
CC ECO:0000269|PubMed:16645022, ECO:0000269|PubMed:19263482,
CC ECO:0000269|PubMed:19438907}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The mature protein migrates in two distinct mature
CC proteins, P16 (16KDa) and P17 (17KDa).
CC -!- MISCELLANEOUS: Ovarian physiology and fertility are controlled by
CC endocrine and paracrine signals. These act in a species-dependent
CC manner and determine the ovulation quota in different mammalian
CC species. While humans, and mammals such as the cow or red deer,
CC normally ovulate only one egg per cycle, other mammals such as mouse
CC and pig can ovulate in excess of ten per cycle. The mechanisms that
CC regulate the species-specific differences in the number of follicles
CC that go onto ovulate during each reproductive cycle are poorly
CC understood. According to PubMed:21970812, mRNA expression levels of
CC GDF9 and BMP15 are tightly coregulated within each species and
CC influence species-specific ovulation-rates.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF082350; AAC99768.1; -; Genomic_DNA.
DR EMBL; AF082349; AAC99768.1; JOINED; Genomic_DNA.
DR EMBL; AJ132405; CAB43531.1; -; Genomic_DNA.
DR EMBL; AL359914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069155; AAH69155.1; -; mRNA.
DR EMBL; BC117264; AAI17265.1; -; mRNA.
DR EMBL; BC117266; AAI17267.1; -; mRNA.
DR CCDS; CCDS14334.1; -.
DR RefSeq; NP_005439.2; NM_005448.2.
DR AlphaFoldDB; O95972; -.
DR BioGRID; 114644; 5.
DR IntAct; O95972; 5.
DR MINT; O95972; -.
DR STRING; 9606.ENSP00000252677; -.
DR GlyGen; O95972; 5 sites.
DR iPTMnet; O95972; -.
DR PhosphoSitePlus; O95972; -.
DR BioMuta; BMP15; -.
DR MassIVE; O95972; -.
DR PaxDb; O95972; -.
DR PeptideAtlas; O95972; -.
DR PRIDE; O95972; -.
DR ProteomicsDB; 51155; -.
DR Antibodypedia; 26314; 358 antibodies from 37 providers.
DR DNASU; 9210; -.
DR Ensembl; ENST00000252677.4; ENSP00000252677.3; ENSG00000130385.6.
DR GeneID; 9210; -.
DR KEGG; hsa:9210; -.
DR MANE-Select; ENST00000252677.4; ENSP00000252677.3; NM_005448.2; NP_005439.2.
DR UCSC; uc011mnw.3; human.
DR CTD; 9210; -.
DR DisGeNET; 9210; -.
DR GeneCards; BMP15; -.
DR HGNC; HGNC:1068; BMP15.
DR HPA; ENSG00000130385; Not detected.
DR MalaCards; BMP15; -.
DR MIM; 300247; gene.
DR MIM; 300510; phenotype.
DR neXtProt; NX_O95972; -.
DR OpenTargets; ENSG00000130385; -.
DR Orphanet; 243; 46,XX gonadal dysgenesis.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR PharmGKB; PA25378; -.
DR VEuPathDB; HostDB:ENSG00000130385; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160940; -.
DR HOGENOM; CLU_055377_0_0_1; -.
DR InParanoid; O95972; -.
DR OMA; VYRHQLH; -.
DR OrthoDB; 724783at2759; -.
DR PhylomeDB; O95972; -.
DR TreeFam; TF316134; -.
DR PathwayCommons; O95972; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; O95972; -.
DR SIGNOR; O95972; -.
DR BioGRID-ORCS; 9210; 16 hits in 686 CRISPR screens.
DR GeneWiki; Bone_morphogenetic_protein_15; -.
DR GenomeRNAi; 9210; -.
DR Pharos; O95972; Tbio.
DR PRO; PR:O95972; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O95972; protein.
DR Bgee; ENSG00000130385; Expressed in secondary oocyte and 5 other tissues.
DR Genevisible; O95972; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0070698; F:type I activin receptor binding; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0060016; P:granulosa cell development; IEA:InterPro.
DR GO; GO:0001541; P:ovarian follicle development; IEA:InterPro.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR015923; BMP-15.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR PANTHER; PTHR11848:SF22; PTHR11848:SF22; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Cytokine; Disease variant; Disulfide bond; Glycoprotein; Growth factor;
KW Phosphoprotein; Premature ovarian failure; Pyrrolidone carboxylic acid;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..267
FT /id="PRO_0000033892"
FT CHAIN 268..392
FT /note="Bone morphogenetic protein 15"
FT /id="PRO_0000033893"
FT MOD_RES 268
FT /note="Pyrrolidone carboxylic acid; in P16 and P17"
FT /evidence="ECO:0000269|PubMed:18227435"
FT MOD_RES 273
FT /note="Phosphoserine; in P16"
FT /evidence="ECO:0000269|PubMed:18227435"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="O-linked (HexNAc...) threonine; in P17"
FT /evidence="ECO:0000269|PubMed:18227435"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 291..357
FT /evidence="ECO:0000250"
FT DISULFID 320..389
FT /evidence="ECO:0000250"
FT DISULFID 324..391
FT /evidence="ECO:0000250"
FT VARIANT 5
FT /note="S -> R (no or minor deleterious effect observed;
FT dbSNP:rs113099187)"
FT /evidence="ECO:0000269|PubMed:19263482"
FT /id="VAR_058974"
FT VARIANT 61
FT /note="R -> Q (in POF4)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058975"
FT VARIANT 61
FT /note="R -> W (in POF4; dbSNP:rs144392417)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058976"
FT VARIANT 68
FT /note="R -> W (in POF4; leads to marked reduction of mature
FT protein production; does not generate a complete recovery
FT of wild-type activity in granulosa cell line transfected
FT with defective mutant and with equal amount of wild-type
FT protein; dbSNP:rs104894763)"
FT /evidence="ECO:0000269|PubMed:16464940,
FT ECO:0000269|PubMed:19263482, ECO:0000269|PubMed:28585349"
FT /id="VAR_058977"
FT VARIANT 76
FT /note="R -> C (in POF4; dbSNP:rs104894766)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058978"
FT VARIANT 76
FT /note="R -> H (in POF4; dbSNP:rs1557279925)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058979"
FT VARIANT 103
FT /note="N -> S (in dbSNP:rs41308602)"
FT /evidence="ECO:0000269|PubMed:16508750,
FT ECO:0000269|PubMed:9849956"
FT /id="VAR_058980"
FT VARIANT 138
FT /note="R -> H (in POF4; leads to marked reduction of mature
FT protein production; does not generate a complete recovery
FT of wild-type activity in granulosa cell line transfected
FT with defective mutant and with equal amount of wild-type
FT protein; dbSNP:rs371418883)"
FT /evidence="ECO:0000269|PubMed:19263482"
FT /id="VAR_058981"
FT VARIANT 148
FT /note="L -> P (in POF4; leads to marked reduction of mature
FT protein production; does not generate a complete recovery
FT of wild-type activity in granulosa cell line transfected
FT with defective mutant and with equal amount of wild-type
FT protein; dbSNP:rs114823607)"
FT /evidence="ECO:0000269|PubMed:16645022,
FT ECO:0000269|PubMed:19263482"
FT /id="VAR_058982"
FT VARIANT 180
FT /note="A -> F (requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058983"
FT VARIANT 180
FT /note="A -> T (in POF4; unknown pathological significance;
FT no or minor deleterious effect detected;
FT dbSNP:rs104894767)"
FT /evidence="ECO:0000269|PubMed:16464940,
FT ECO:0000269|PubMed:16508750, ECO:0000269|PubMed:16645022,
FT ECO:0000269|PubMed:19263482"
FT /id="VAR_058984"
FT VARIANT 196
FT /note="N -> K (in POF4)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058985"
FT VARIANT 200
FT /note="H -> Y (in dbSNP:rs202165852)"
FT /evidence="ECO:0000269|PubMed:19438907"
FT /id="VAR_066932"
FT VARIANT 206
FT /note="R -> H (in POF4; dbSNP:rs782516193)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058986"
FT VARIANT 221
FT /note="W -> R (in POF4; dbSNP:rs375284458)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058987"
FT VARIANT 235
FT /note="Y -> C (in ODG2; dominant-negative effect; may cause
FT relevant modifications in the conformation of the precursor
FT protein possibly leading to altered processing and impaired
FT activation of latent forms or to abnormal dimerization;
FT dbSNP:rs104894765)"
FT /evidence="ECO:0000269|PubMed:15136966,
FT ECO:0000269|PubMed:16464940"
FT /id="VAR_021195"
FT VARIANT 243
FT /note="I -> V (in POF4; dbSNP:rs782379521)"
FT /evidence="ECO:0000269|PubMed:16508750"
FT /id="VAR_058988"
FT VARIANT 263
FT /note="L -> LL (no or minor deleterious effect detected)"
FT /evidence="ECO:0000269|PubMed:16464940,
FT ECO:0000269|PubMed:16508750, ECO:0000269|PubMed:16645022,
FT ECO:0000269|PubMed:19263482"
FT /id="VAR_058989"
FT VARIANT 329
FT /note="R -> C (in POF4; dbSNP:rs782375794)"
FT /evidence="ECO:0000269|PubMed:19438907"
FT /id="VAR_066933"
SQ SEQUENCE 392 AA; 45055 MW; A957275EF275A2E8 CRC64;
MVLLSILRIL FLCELVLFME HRAQMAEGGQ SSIALLAEAP TLPLIEELLE ESPGEQPRKP
RLLGHSLRYM LELYRRSADS HGHPRENRTI GATMVRLVKP LTNVARPHRG TWHIQILGFP
LRPNRGLYQL VRATVVYRHH LQLTRFNLSC HVEPWVQKNP TNHFPSSEGD SSKPSLMSNA
WKEMDITQLV QQRFWNNKGH RILRLRFMCQ QQKDSGGLEL WHGTSSLDIA FLLLYFNDTH
KSIRKAKFLP RGMEEFMERE SLLRRTRQAD GISAEVTASS SKHSGPENNQ CSLHPFQISF
RQLGWDHWII APPFYTPNYC KGTCLRVLRD GLNSPNHAII QNLINQLVDQ SVPRPSCVPY
KYVPISVLMI EANGSILYKE YEGMIAESCT CR
