BMP15 (bone morphogenetic protein 15)

Gene

• Entrez ID: 9210
• Gene name: Bone morphogenetic protein 15
• Gene symbol: BMP15
• Synonyms (NCBI Gene): GDF9B, ODG2, POF4
• Chromosome: X
• Chromosome location: Xp11.22
• Summary: This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894763	C>T	Likely-benign, pathogenic, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs104894765	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs104894766	C>T	Pathogenic	Coding sequence variant, missense variant
rs104894767	G>A,T	Likely-benign, pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs137853320	C>T	Pathogenic	Coding sequence variant, stop gained

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005125	Function	Cytokine activity	IBA
GO:0005125	Function	Cytokine activity	IEA
GO:0005515	Function	Protein binding	IPI	33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0007178	Process	Cell surface receptor protein serine/threonine kinase signaling pathway	IBA
GO:0007292	Process	Female gamete generation	IEA
GO:0007292	Process	Female gamete generation	TAS	9849956
GO:0008083	Function	Growth factor activity	IEA

Other IDs

• MIM: 300247
• HGNC: 1068
• e!Ensembl: ENSG00000130385

Protein

• UniProt ID: O95972
• Protein name: Bone morphogenetic protein 15 (BMP-15) (Growth/differentiation factor 9B) (GDF-9B)
• Protein function: May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00019	TGF_beta	290 → 391	Transforming growth factor beta like domain	Domain

• Sequence:

  MVLLSILRILFLCELVLFMEHRAQMAEGGQSSIALLAEAPTLPLIEELLEESPGEQPRKP
  RLLGHSLRYMLELYRRSADSHGHPRENRTIGATMVRLVKPLTNVARPHRGTWHIQILGFP
  LRPNRGLYQLVRATVVYRHHLQLTRFNLSCHVEPWVQKNPTNHFPSSEGDSSKPSLMSNA
  WKEMDITQLVQQRFWNNKGHRILRLRFMCQQQKDSGGLELWHGTSSLDIAFLLLYFNDTH
  KSIRKAKFLPRGMEEFMERESLLRRTRQADGISAEVTASSSKHSGPENNQCSLHPFQISF
  RQLGWDHWIIAPPFYTPNYCKGTCLRVLRDGLNSPNHAIIQNLINQLVDQSVPRPSCVPY
  KYVPISVLMIEANGSILYKEYEGMIAESCTCR

• Sequence length: 392

Pathways

KEGG:

Cytokine-cytokine receptor interaction
Ovarian steroidogenesis

Reactome:

Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Post-translational protein phosphorylation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Genetic non-acquired premature ovarian failure	Likely pathogenic	rs782325962, rs782540417	RCV001661770 RCV001663380	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian dysgenesis 2	Pathogenic; Likely pathogenic	rs371418883, rs782516193, rs375284458, rs782379521, rs104894765, rs1923115287	RCV002249300 RCV002249301 RCV002249302 RCV002249303 RCV000012225 RCV001249552	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Premature ovarian failure 4	Pathogenic	rs137853320	RCV000012228	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
46 XX GONADAL DYSGENESIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BMP15-related disorder	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GONADAL DYSGENESIS, 46,XX	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MALIGNANT TERATOMA OF OVARY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian dysgenesis	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN FAILURE, PREMATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYSTIC OVARY SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
46,XX gonadal dysgenesis	46, XX gonadal dysgenesis	Orphanet			★☆☆☆☆ Found in Text Mining only
Amenorrhea	Amenorrhea	Pubtator	19263482, 31957178, 35232444	Associate	★☆☆☆☆ Found in Text Mining only
Anovulation	Anovulation	Pubtator	17905236	Associate	★☆☆☆☆ Found in Text Mining only
Arachnodactyly	Arachnodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis	Gonadal Dysgenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis, 46,XX	Gonadal Dysgenesis	BEFREE	15136966, 17826728		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gonadal Dysgenesis, 46,XX	Gonadal Dysgenesis	ORPHANET_DG	15136966		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gonadal hypoplasia	Gonadal hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	35861920	Associate	★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	BEFREE	22825968		★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	17905236	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Primary ovarian failure	Ovarian Failure	Orphanet			★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	BEFREE	22335445		★☆☆☆☆ Found in Text Mining only
Osteoporosis of vertebrae	Osteoporosis of vertebrae	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ovarian dysgenesis	Ovarian Dysgenesis	BEFREE	15136966		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian dysgenesis	Ovarian Dysgenesis	GENOMICS_ENGLAND_DG	19486016		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Dysgenesis 2	Ovarian Dysgenesis	UNIPROT_DG	15136966, 16464940, 16508750, 16645022, 19263482, 19438907		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ovarian Dysgenesis 2	Ovarian dysgenesis	Pubtator	15136966	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ovarian Dysgenesis 2	Ovarian Dysgenesis	GENOMICS_ENGLAND_DG	19486016, 26350204		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ovarian Dysgenesis 2	Ovarian Dysgenesis	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ovarian Dysgenesis 2	Ovarian Dysgenesis	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ovarian Failure, Premature	Ovarian Failure	BEFREE	11056243, 16464940, 16508750, 16645022, 17027369, 17464588, 17826728, 19263482, 20364024, 20547206, 21226076, 22014425, 23107817, 24147118, 25246117, 25954833, 25988799, 28094433, 28359091, 29169851, 29544636, 31607184		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Failure, Premature	Ovarian Failure	LHGDN	16645022		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Failure, Premature	Ovarian Failure	GENOMICS_ENGLAND_DG	19486016		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Hyperstimulation Syndrome	Ovarian Hyperstimulation Syndrome	BEFREE	16788381, 21561809, 21565556		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35232444, 38358476	Associate	★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	11056243, 11889206, 17905236, 19376510, 21669410, 22014425, 22825968, 23912750, 25172094, 28903889, 28983616, 29544636, 31211369		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	LHGDN	17905236		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	19376510, 21669410, 22825968, 23912750, 25172094, 36151730	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	CTD_human_DG	22825968		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature Menopause	Premature Menopause	BEFREE	11056243, 16464940, 16508750, 16645022, 17027369, 17464588, 17826728, 19263482, 20364024, 21226076, 22014425, 24147118, 25246117, 25954833, 25988799, 28094433, 28359091, 29169851, 29544636, 31392662, 31607184		★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	HPO_DG			★☆☆☆☆ Found in Text Mining only
Premature Ovarian Failure 4	Premature Ovarian Failure	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature Ovarian Failure 4	Premature Ovarian Failure	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Fibrosis	Pulmonary Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pure Gonadal Dysgenesis, 46, XX	46,XX gonadal dysgenesis	ORPHANET_DG	15136966		★☆☆☆☆ Found in Text Mining only
Sclerocystic Ovaries	Sclerocystic Ovaries	CTD_human_DG	22825968		★☆☆☆☆ Found in Text Mining only
Secondary physiologic amenorrhea	Secondary Physiologic Amenorrhea	BEFREE	16508750, 19263482		★☆☆☆☆ Found in Text Mining only
Secondary physiologic amenorrhea	Secondary Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Streak ovary	Streak ovary	BEFREE	21561809		★☆☆☆☆ Found in Text Mining only
Streak ovary	Streak ovary	HPO_DG			★☆☆☆☆ Found in Text Mining only
Subfertility	Subfertility	BEFREE	24147118, 28903889		★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner syndrome	Pubtator	24324027	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Anomalies	Uterine Anomalies	HPO_DG			★☆☆☆☆ Found in Text Mining only