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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BMP15
bone morphogenetic protein 15
Chromosome X Β· Xp11.22
NCBI Gene: 9210Ensembl: ENSG00000130385.6HGNC: HGNC:1068UniProt: O95972
87PubMed Papers
22Diseases
0Drugs
12Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcytokine activitycell surface receptor protein serine/threonine kinase signaling pathwayGO:000561546,XX gonadal dysgenesisprimary ovarian insufficiencypremature ovarian failure 446 XX gonadal dysgenesis
✦AI Summary

BMP15 (bone morphogenetic protein 15) is an oocyte-secreted factor exclusively expressed in oocytes that plays a critical role in ovarian folliculogenesis and female fertility 1. As a member of the transforming growth factor beta superfamily, BMP15 modulates granulosa cell fate and oocyte developmental competence through paracrine signaling 2. The protein stimulates follicle growth and cumulus cell expansion, with particular importance in the oocyte-cumulus cell dialog that determines oocyte meiotic competence 3. BMP15 mutations cause primary ovarian insufficiency (POI) through impaired oogenesis and activation of macrophage-mediated ovarian failure pathways 4. Genetic studies confirm BMP15 as a major gene causing POI, with heterozygous mutations increasing ovulation rate in sheep while homozygous mutations cause infertility 1. In humans, BMP15 mutations account for a subset of genetic POI cases and are among the few single genes with unequivocal deleterious effects across populations 5. Additionally, BMP15 expression is downregulated in polycystic ovary syndrome, where androgen excess impairs follicular development 6. The therapeutic potential of BMP15 modulation remains an important avenue for treating female infertility and ovarian dysfunction.

Sources cited
1
BMP15 is expressed exclusively in oocytes, is a TGFbeta family member, and mutations cause infertility in sheep with species-dependent effects
PMID: 12044914
2
BMP15 is an oocyte-secreted factor modulating granulosa cell fate and oocyte developmental competence with clinical relevance to POI and PCOS
PMID: 29544636
3
BMP15 participates in oocyte-cumulus cell dialog and controls cumulus cell differentiation during oocyte maturation
PMID: 16959524
4
BMP15 is a conserved regulator of ovarian development; germline loss impairs oogenesis and initiates macrophage-driven ovarian failure
PMID: 37992158
5
BMP15 is among genes with unequivocal deleterious effects in POI, identified through candidate gene studies
PMID: 26243799
6
BMP15 expression is decreased in PCOS granulosa cells exposed to androgen excess, impairing follicular development
PMID: 35237237
Disease Associationsβ“˜22
46,XX gonadal dysgenesisOpen Targets
0.72Strong
primary ovarian insufficiencyOpen Targets
0.72Strong
premature ovarian failure 4Open Targets
0.47Moderate
46 XX gonadal dysgenesisOpen Targets
0.37Weak
Primary amenorrheaOpen Targets
0.34Weak
genetic non-acquired premature ovarian failureOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
polycystic ovary syndromeOpen Targets
0.12Weak
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.06Suggestive
aromatase deficiencyOpen Targets
0.06Suggestive
Familial hyperprolactinemiaOpen Targets
0.06Suggestive
familial hyperprolactinemiaOpen Targets
0.06Suggestive
infertilityOpen Targets
0.06Suggestive
Perrault syndrome 6Open Targets
0.05Suggestive
46,XX ovotesticular disorder of sex developmentOpen Targets
0.05Suggestive
ring chromosome YOpen Targets
0.05Suggestive
premature ovarian failure 18Open Targets
0.05Suggestive
premature menopauseOpen Targets
0.05Suggestive
Ovarian dysgenesis 2UniProt
Premature ovarian failure 4UniProt
Pathogenic Variants12
NM_005448.2(BMP15):c.166C>T (p.Gln56Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 56
NM_005448.2(BMP15):c.727A>G (p.Ile243Val)Pathogenic
Ovarian dysgenesis 2
β˜…β˜†β˜†β˜†2022β†’ Residue 243
NM_005448.2(BMP15):c.413G>A (p.Arg138His)Pathogenic
Ovarian dysgenesis 2
β˜…β˜†β˜†β˜†2022β†’ Residue 138
NM_005448.2(BMP15):c.617G>A (p.Arg206His)Pathogenic
Ovarian dysgenesis 2
β˜…β˜†β˜†β˜†2022β†’ Residue 206
NM_005448.2(BMP15):c.661T>C (p.Trp221Arg)Pathogenic
Ovarian dysgenesis 2
β˜…β˜†β˜†β˜†2022β†’ Residue 221
NC_000023.10:g.50653777_50689335del35559Pathogenic
Primary amenorrhea
β˜…β˜†β˜†β˜†2018
NM_005448.2(BMP15):c.-49_*34del (p.Met1fs)Pathogenic
Ovarian dysgenesis 2
β˜†β˜†β˜†β˜†2019β†’ Residue 1
NM_005448.2(BMP15):c.704A>G (p.Tyr235Cys)Pathogenic
Ovarian dysgenesis 2
β˜†β˜†β˜†β˜†2019β†’ Residue 235
NM_005448.2(BMP15):c.462del (p.Trp155fs)Likely pathogenic
Ovarian dysgenesis 2
β˜†β˜†β˜†β˜†2019β†’ Residue 155
NM_005448.2(BMP15):c.919C>T (p.His307Tyr)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 307
NM_005448.2(BMP15):c.208A>C (p.Met70Leu)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 70
NM_005448.2(BMP15):c.631C>T (p.Gln211Ter)Pathogenic
Premature ovarian failure 4
β˜†β˜†β˜†β˜†2006β†’ Residue 211
View on ClinVar β†—
Related Genes
FSTProtein interaction89%POF1BProtein interaction88%AMHProtein interaction81%BMPR1AProtein interaction81%BMPR1BProtein interaction81%BMPR2Protein interaction81%
Tissue Expression6 tissues
Heart
0%
Lung
0%
Bone Marrow
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
BMP15FSTPOF1BAMHBMPR1ABMPR1BBMPR2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O95972
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
2.38LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF1.13 [0.59–2.38]
RankingsWhere BMP15 stands among ~20K protein-coding genes
  • #5,460of 20,598
    Most Researched87
  • #2,673of 5,498
    Most Pathogenic Variants12
  • #17,860of 17,882
    Most Constrained (LOEUF)2.38
Genes detectedBMP15
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics of primary ovarian insufficiency: new developments and opportunities.
PMID: 26243799
Hum Reprod Update Β· 2015
1.00
2
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
0.90
3
Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development.
PMID: 35237237
Front Endocrinol (Lausanne) Β· 2022
0.80
4
Molecular Aspects and Clinical Relevance of GDF9 and BMP15 in Ovarian Function.
PMID: 29544636
Vitam Horm Β· 2018
0.70
5
Bmp15 mutations and ovarian function.
PMID: 12044914
Mol Cell Endocrinol Β· 2002
0.60