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   24-JAN-2024, entry version 182.
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}.
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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   GlyCosmos; O95972; 5 sites, No reported glycans.
DR   GlyGen; O95972; 5 sites.
DR   iPTMnet; O95972; -.
DR   PhosphoSitePlus; O95972; -.
DR   BioMuta; BMP15; -.
DR   MassIVE; O95972; -.
DR   PaxDb; 9606-ENSP00000252677; -.
DR   PeptideAtlas; O95972; -.
DR   ProteomicsDB; 51155; -.
DR   Antibodypedia; 26314; 396 antibodies from 38 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   AGR; HGNC:1068; -.
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; 5301288at2759; -.
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 769 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 cell types or tissues.
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:0007292; P:female gamete generation; TAS:ProtInc.
DR   CDD; cd19402; TGF_beta_GDF9B; 1.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 1.
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:SF22; BONE MORPHOGENETIC PROTEIN 15; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   PRINTS; PR00669; INHIBINA.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; Cystine-knot cytokines; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
DR   Genevisible; O95972; HS.
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; uncertain significance; no or minor
FT                   deleterious effect detected; 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
//