BMP15

Summary

BMP15 (bone morphogenetic protein 15, HGNC:1068) is a protein-coding gene on chromosome Xp11.22, encoding Bone morphogenetic protein 15 (O95972). May be involved in follicular development.

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 gene expression. The encoded preproprotein is proteolytically processed to generate subunits of a disulfide-linked homodimer, or alternatively, a heterodimer, with the related protein, growth differentiation factor 9 (GDF9). This protein plays a role in oocyte maturation and follicular development, through activation of granulosa cells. Defects in this gene are the cause of ovarian dysgenesis and are associated with premature ovarian failure.

Source: NCBI Gene 9210 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ovarian dysgenesis 2 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 89 total — 10 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_005448

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1068
Approved symbol	BMP15
Name	bone morphogenetic protein 15
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	GDF9B
Ensembl gene	ENSG00000130385
Ensembl biotype	protein_coding
OMIM	300247
Entrez	9210

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000252677

RefSeq mRNA: 1 — MANE Select: NM_005448 NM_005448

CCDS: CCDS14334

Canonical transcript exons

ENST00000252677 — 2 exons

Exon	Start	End
ENSE00000833627	50910735	50911111
ENSE00000894464	50915757	50916641

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 99.19.

Top tissues by expression

262 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.19	gold quality
oocyte	CL:0000023	98.75	gold quality
pancreatic ductal cell	CL:0002079	75.32	silver quality
tibialis anterior	UBERON:0001385	68.36	silver quality
ileal mucosa	UBERON:0000331	65.45	silver quality
decidua	UBERON:0002450	56.55	gold quality
mucosa of paranasal sinus	UBERON:0005030	55.58	gold quality
epithelial cell of pancreas	CL:0000083	53.85	gold quality
deltoid	UBERON:0001476	53.72	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
quadriceps femoris	UBERON:0001377	49.74	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, NR6A1

Literature-anchored findings (GeneRIF, showing 40)

• Data show that bone morphogenetic protein-15 activates the Smad pathway in granulosa cell models. (PMID:12419820)
• interaction with growth and differentiation factor-9 and implication in aberrant ovarian phenotype (PMID:12446716)
• BMP-15 and GDF-9 have roles in fertility; critical sequences are determined by mutagenesis (PMID:14970198)
• Hypergonadotropic ovarian failure is associated with an inherited mutation of human bone morphogenetic protein-15 gene. (PMID:15136966)
• comparison of the molecular characteristics of BMP-15 of polyovulatory mice with that of monoovulatory humans (PMID:15809424)
• Missense mutations in the BMP15 gene are associated with ovarian failure (PMID:16508750)
• although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in premature ovarian failure (PMID:16645022)
• Mutational screening of the bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes in a population with premature ovarian failure (POF) identified no new mutations. (PMID:17027369)
• a BMP15 alteration,as a possible cause of ovarian failure, previously described as a mutation, is instead a polymorphism (PMID:17826728)
• We analyzed two polymorphisms (-9C>G and IVS1+905A>G) within the BMP15 gene in women from Spain with polycystic ovary syndrome (PCOS). BMP15 gene does not seem to be associated with PCOS. (PMID:17905236)
• phosphorylation state of rhBMP-15 and rhGDF-9 is a determinant of their agonistic and antagonistic activities (PMID:18006624)
• characterization of the post-translational modification of recombinant BMP-15 mature protein (P16 and P17); findings are the first knowledge of the structure of rhBMP-15 mature protein toward understanding the molecular basis of BMP-15 function (PMID:18227435)
• Findings indicate the role of BMP-15 in vivo in promoting follicle growth and preventing follicle maturation, resulting in an early decline in the ovarian reserve of transgenic mice. (PMID:18308851)
• BMP15 variants do not play a significant role in human dizygotic twinning. (PMID:18614612)
• The BMP-15 protein is expressed already at primordial stages in fetuses, girls, and women, and its mRNA transcripts in fetuses and girls. (PMID:18980767)
• These findings support the concept that an adequate amount of BMP15 secreted in the follicular fluid is critical for female fertility. (PMID:19263482)
• demonstrated for having a role in the pathogenesis of Premature Ovarian Failure (PMID:19346101)
• No significant difference was detected in the expression of BMP-15 between patients with polycystic ovary syndrome and controls. (PMID:19376510)
• in Chinese premature ovarian failure patients, study revealed 3 variants in coding region of BMP15 - an insertion p.262insLeu in 5 patients & 2 novel mutations c.985C>T (p.Arg329Cys)& c.598C>T (p.His200Tyr) (PMID:19438907)
• Bone morphogenetic protein 15 (BMP15) acts as a BMP and Wnt inhibitor during early embryogenesis. (PMID:19553676)
• Bone morphogenetic protein-15 is expressed in oocytes and cumulus granulosa cells and may play an important role in the hCG-induced oocyte final maturation and corpus luteum (CL) formation (PMID:19635612)
• Results describe the expression and characterization of recombinant human BMP15, which is biologically active and very stable, and can induce the expression of a variety of mouse granulosa cell genes. (PMID:19651638)
• Data show that show that Golgi apparatus casein kinase (G-CK) catalyzes the phosphorylation of rhBMP-15 and rhGDF-9. (PMID:20067794)
• data demonstrate that polymorphisms in major folliculogenesis genes, GDF9, BMP15, AMH, and AMHR2, are not associated with polycystic ovary syndrome susceptibility. (PMID:20236105)
• Various missense variants of the BMP15 gene were identified among patients with premature ovarian failure. (PMID:20364024)
• Impaired production of BMP15 and GDF9 mature proteins derived from proproteins with mutation in the proregion. (PMID:20547206)
• Results describe a purified untagged human BMP15 mature region, which is stable and highly bioactive in human and rodent granulosa cells and as such is of importance for studies on human fertility. (PMID:20937357)
• Integral role of GDF-9 and BMP-15 in ovarian function. (PMID:21226076)
• There were no statistically significant differences in embryo quality among the patients regarding follicular fluid BMP15 expression status. (PMID:21496799)
• BMP15 is associated with high response to ovarian stimulation. (PMID:21565556)
• In the samples from girls/women, the number of developing follicles was greater with GDF9 or BMP15 alone than with no BMP15 or GDF9. (PMID:21632818)
• The expression of GDF9 and BMP15 in oocytes from patients with polycystic ovary syndrome cannot reach the normal level even after ovarian stimulation. (PMID:21669410)
• BMP15 gene mutations may be potentially associated with polycystic ovarian syndrome patients. (PMID:22014425)
• BMP15 uses preferentially BMPR1B as its type I receptor, suggesting an important role for the BMPR1B receptor in human female fertility (PMID:22294741)
• the activation of bone morphogenetic protein 15 gene (BMP15) during the differentiation of human amniotic fluid stem cells (hAFSCs) into oocyte-like cells (PMID:22356426)
• This study evaluated the levels of bone morphogenetic protein receptors BMPRIB and BMPRII mRNA in goat follicles and the effects of bone morphogenetic protein-15 (BMP-15) on the in vitro development of cultured preantral follicles. (PMID:22382392)
• BMP15 and GDF9 transcript levels increase in mature oocytes from women with polycystic ovary syndrome after ovarian stimulation, and might inhibit the progesterone secretion by follicular cells (PMID:22825968)
• genetic association studies in population of women in Spain: Data suggest an association between an SNP in BMP15 (rs3897937) and age at menopause; thus, duration of fertility in women may have genetic determinants involved in estrogen metabolism. (PMID:23173577)
• Data from cultured mouse preantral follicles suggest that [human recombinant] BMP15 promotes follicle growth in short term (24 hours) incubation; subsequently BMP15 (48-72 hours) causes follicular atresia with increased granulosa cell apoptosis. (PMID:23782946)
• BMP15 down-regulates StAR expression and decreases progesterone production in human granulosa cells, likely via ALK3-mediated SMAD1/5/8 signaling. (PMID:24140593)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmp15	ENSDARG00000037491
mus_musculus	Bmp15	ENSMUSG00000023279
rattus_norvegicus	Bmp15	ENSRNOG00000002984

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Bone morphogenetic protein 15 — O95972 (reviewed: O95972)

Alternative names: Growth/differentiation factor 9B

All UniProt accessions (1): O95972

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth.

Subunit / interactions. Homodimer. But, in contrast to other members of this family, cannot be disulfide-linked.

Subcellular location. Secreted.

Disease relevance. Ovarian dysgenesis 2 (ODG2) [MIM:300510] A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. The disease is caused by variants affecting the gene represented in this entry. Premature ovarian failure 4 (POF4) [MIM:300510] An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The mature protein migrates in two distinct mature proteins, P16 (16KDa) and P17 (17KDa). Ovarian physiology and fertility are controlled by endocrine and paracrine signals. These act in a species-dependent manner and determine the ovulation quota in different mammalian species. While humans, and mammals such as the cow or red deer, normally ovulate only one egg per cycle, other mammals such as mouse and pig can ovulate in excess of ten per cycle. The mechanisms that regulate the species-specific differences in the number of follicles that go onto ovulate during each reproductive cycle are poorly understood. According to PubMed:21970812, mRNA expression levels of GDF9 and BMP15 are tightly coregulated within each species and influence species-specific ovulation-rates.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_005439* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019

UniProt features (32 total): sequence variant 19, glycosylation site 5, disulfide bond 3, modified residue 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95972-F1	72.64	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 268, 273

Disulfide bonds (3): 291–357, 320–389, 324–391

Glycosylation sites (5): 87, 147, 237, 277, 373

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 125 (showing top): GOMF_GROWTH_FACTOR_ACTIVITY, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOMF_CYTOKINE_ACTIVITY, GOBP_FEMALE_GAMETE_GENERATION, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, MATZUK_CUMULUS_EXPANSION, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KOYAMA_SEMA3B_TARGETS_DN, chrXp11, REACTOME_REGULATION_OF_INSULIN_LIKE_GROWTH_FACTOR_IGF_TRANSPORT_AND_UPTAKE_BY_INSULIN_LIKE_GROWTH_FACTOR_BINDING_PROTEINS_IGFBPS, CRX_DN.V1_UP, NRL_DN.V1_DN, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY

GO Biological Process (2): cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), female gamete generation (GO:0007292)

GO Molecular Function (3): cytokine activity (GO:0005125), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular region (GO:0005576), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of proteins	2
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
receptor ligand activity	2
cellular anatomical structure	2
enzyme-linked receptor protein signaling pathway	1
gamete generation	1
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP15	GDF9	O60383	968
BMP15	BMPR2	Q13873	950
BMP15	BMPR1B	P78366	948
BMP15	FIGLA	Q6QHK4	946
BMP15	NOBOX	O60393	935
BMP15	FSHR	P23945	930
BMP15	FOXL2	P58012	891
BMP15	FST	P19883	885
BMP15	POF1B	Q8WVV4	871
BMP15	BMPR1A	P36894	826
BMP15	AMH	P03971	802
BMP15	DIAPH2	O60879	779
BMP15	FMR1	Q06787	767
BMP15	IGF1	P01343	755
BMP15	LHCGR	P22888	741

IntAct

6 interactions, top by confidence:

A	B	Type	Score
BMP15	AMD1	psi-mi:“MI:0914”(association)	0.530
BMP15	DCAF6	psi-mi:“MI:0915”(physical association)	0.500
FAM20C	BMP15	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): AMD1 (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), DCAF6 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), AMD1 (Affinity Capture-MS), DCAF6 (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), BMP15 (Affinity Capture-MS), DCAF6 (Affinity Capture-MS), AMD1 (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), BMP15 (Proximity Label-MS)

ESM2 similar proteins: A2VDJ0, A9CB18, O13048, O18752, O18753, O60383, O70183, O77681, O95813, O95972, P09529, P12645, P14082, P17491, P20722, P21237, P22003, P22004, P22444, P23363, P25429, P27093, P49002, P49003, Q04906, Q04999, Q07105, Q08DV9, Q0EAB7, Q28GB8, Q3SAT7, Q3U3D7, Q66NC0, Q6PX77, Q7T2X6, Q7T2X7, Q7YRB4, Q800B9, Q8BHE5, Q8QG74

Diamond homologs: A8E7N9, G5EEL5, O08717, O18828, O18830, O19006, O42222, O46564, O46576, O88959, O95390, O95393, O95972, P03970, P07713, P07995, P08476, P09534, P12643, P12644, P12645, P18075, P18331, P20722, P20863, P21274, P21275, P22003, P22004, P22444, P23359, P25703, P27092, P27539, P30884, P30885, P30886, P34820, P34821, P34822

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BMP15	up-regulates	BMPR2	binding
BMP15	up-regulates	BMPR1A/1B/2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

89 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	3
Uncertain significance	50
Likely benign	8
Benign	9

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
11470	NM_005448.2(BMP15):c.704A>G (p.Tyr235Cys)	Pathogenic
11473	NM_005448.2(BMP15):c.631C>T (p.Gln211Ter)	Pathogenic
153068	GRCh38/hg38 Xp11.3-11.22(chrX:46971389-54130971)x3	Pathogenic
1685573	NM_005448.2(BMP15):c.413G>A (p.Arg138His)	Pathogenic
1685574	NM_005448.2(BMP15):c.617G>A (p.Arg206His)	Pathogenic
1685575	NM_005448.2(BMP15):c.661T>C (p.Trp221Arg)	Pathogenic
1685576	NM_005448.2(BMP15):c.727A>G (p.Ile243Val)	Pathogenic
2078651	NM_005448.2(BMP15):c.166C>T (p.Gln56Ter)	Pathogenic
549656	NC_000023.10:g.50653777_50689335del35559	Pathogenic
973167	NM_005448.2(BMP15):c.-49_*34del (p.Met1fs)	Pathogenic
1256010	NM_005448.2(BMP15):c.208A>C (p.Met70Leu)	Likely pathogenic
1256036	NM_005448.2(BMP15):c.919C>T (p.His307Tyr)	Likely pathogenic
973166	NM_005448.2(BMP15):c.462del (p.Trp155fs)	Likely pathogenic

SpliceAI

106 predictions. Top by Δscore:

Variant	Effect	Δscore
X:50911109:GAG:G	donor_gain	1.0000
X:50911110:AGGTG:A	donor_loss	1.0000
X:50911112:G:GG	donor_gain	1.0000
X:50911107:CAGAG:C	donor_gain	0.9900
X:50911113:T:A	donor_loss	0.9900
X:50915747:A:AG	acceptor_gain	0.9900
X:50915748:C:G	acceptor_gain	0.9900
X:50915752:T:A	acceptor_gain	0.9900
X:50915755:A:AG	acceptor_gain	0.9900
X:50915756:G:GT	acceptor_gain	0.9900
X:50915756:GGT:G	acceptor_gain	0.9900
X:50915756:GGTA:G	acceptor_gain	0.9900
X:50915756:GGTAC:G	acceptor_gain	0.9900
X:50911108:AGAG:A	donor_gain	0.9800
X:50911109:GAGG:G	donor_gain	0.9800
X:50911110:AG:A	donor_gain	0.9800
X:50911111:GG:G	donor_gain	0.9800
X:50915755:AG:A	acceptor_gain	0.9800
X:50915756:GG:G	acceptor_gain	0.9800
X:50911112:GTGA:G	donor_gain	0.9400
X:50911110:AGGT:A	donor_gain	0.9300
X:50911111:GGTG:G	donor_gain	0.9300
X:50911113:T:TC	donor_gain	0.9300
X:50911114:G:GT	donor_gain	0.9300
X:50911070:G:GT	donor_gain	0.9200
X:50911097:C:T	donor_gain	0.9100
X:50911108:AGAGG:A	donor_gain	0.9100
X:50911109:GAGGT:G	donor_gain	0.9000
X:50915752:TGCAG:T	acceptor_gain	0.8700
X:50915753:GCAGG:G	acceptor_gain	0.8700

AlphaMissense

2567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:50916386:T:A	C320S	0.991
X:50916387:G:C	C320S	0.991
X:50916299:T:A	C291S	0.986
X:50916300:G:C	C291S	0.986
X:50916388:T:G	C320W	0.986
X:50916387:G:A	C320Y	0.985
X:50916497:T:A	C357S	0.984
X:50916498:G:C	C357S	0.984
X:50916524:A:C	S366R	0.983
X:50916526:T:A	S366R	0.983
X:50916526:T:G	S366R	0.983
X:50916326:T:C	F300L	0.982
X:50916328:C:A	F300L	0.982
X:50916328:C:G	F300L	0.982
X:50916498:G:A	C357Y	0.982
X:50916595:T:G	C389W	0.982
X:50916593:T:A	C389S	0.981
X:50916594:G:C	C389S	0.981
X:50916499:T:G	C357W	0.980
X:50916594:G:A	C389Y	0.980
X:50916387:G:T	C320F	0.979
X:50916497:T:C	C357R	0.977
X:50915783:T:C	F119L	0.975
X:50915785:T:A	F119L	0.975
X:50915785:T:G	F119L	0.975
X:50916327:T:G	F300C	0.974
X:50916585:C:A	A386D	0.974
X:50916531:T:C	L368P	0.973
X:50916599:T:A	C391S	0.973
X:50916599:T:C	C391R	0.973

dbSNP variants (sampled 300 via entrez): RS1000414323 (X:50909651 C>A,T), RS1000807740 (X:50911204 G>T), RS1002233057 (X:50912989 C>T), RS1002883529 (X:50913351 C>T), RS1002978493 (X:50914301 G>A,C), RS1006948081 (X:50914257 C>A,G,T), RS1007163554 (X:50914128 G>A), RS1008418535 (X:50915828 A>G), RS1008933682 (X:50909728 T>C), RS1008944821 (X:50909354 C>T), RS1009280471 (X:50911273 G>A), RS1010942262 (X:50913867 A>G), RS1010994604 (X:50913497 T>A), RS1011277431 (X:50915089 C>A), RS1011329879 (X:50914675 G>C)

Disease associations

OMIM: gene MIM:300247 | disease phenotypes: MIM:300510

GenCC curated gene-disease

Disease	Classification	Inheritance
ovarian dysgenesis 2	Strong	X-linked
46 XX gonadal dysgenesis	Supportive	Autosomal dominant

Mondo (4): ovarian dysgenesis 2 (MONDO:0010349), premature ovarian failure 4 (MONDO:0800317), primary amenorrhea (MONDO:1060208), 46 XX gonadal dysgenesis (MONDO:0009299)

Orphanet (2): 46,XX gonadal dysgenesis (Orphanet:243), Rare genetic premature ovarian failure (Orphanet:485382)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000013	Hypoplasia of the uterus
HP:0000062	Ambiguous genitalia
HP:0000133	Gonadal dysgenesis
HP:0000144	Decreased fertility
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000869	Secondary amenorrhea
HP:0000938	Osteopenia
HP:0001007	Hirsutism
HP:0001166	Arachnodactyly
HP:0001251	Ataxia
HP:0001417	X-linked inheritance
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002206	Pulmonary fibrosis
HP:0002225	Sparse pubic hair
HP:0002750	Delayed skeletal maturation
HP:0003621	Juvenile onset
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0005625	Osteoporosis of vertebrae
HP:0008209	Premature ovarian insufficiency
HP:0008214	Decreased serum estradiol
HP:0008684	Aplasia/hypoplasia of the uterus
HP:0009888	Abnormality of secondary sexual hair
HP:0010311	Aplasia/Hypoplasia of the breasts
HP:0010464	Streak ovary

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D023961	Gonadal Dysgenesis, 46,XX	C12.050.351.875.253.064.249; C12.050.351.875.253.309.193; C12.200.706.316.064.249; C12.200.706.316.309.193; C12.800.316.064.249; C12.800.316.309.193; C16.131.939.316.064.249; C16.131.939.316.309.193; C19.391.119.064.249; C19.391.119.309.193
C564499	Ovarian Dysgenesis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	decreases expression, increases activity, affects binding	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Estradiol	increases reaction, affects cotreatment, decreases reaction, increases abundance	1
Methylmercury Compounds	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

3 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice