Ovarian dysgenesis 2

Summary

Ovarian dysgenesis 2 (MONDO:0010349) is a disease caused by BMP15 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BMP15 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian dysgenesis 2
Mondo ID	MONDO:0010349
MeSH	C564499
OMIM	300510
DOID	DOID:0080494, DOID:0080861
UMLS	C1845294
MedGen	336903
GARD	0018040
Is cancer (heuristic)	no

Also known as: BMP15 primary ovarian failure · ODG2 · ovarian dysgenesis 2 · ovarian dysgenesis type 2 · primary ovarian failure caused by mutation in BMP15

Data availability: 28 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › gonadal dysgenesis › 46 XX gonadal dysgenesis › ovarian dysgenesis 2

Related subtypes (10): SERKAL syndrome, ovarian dysgenesis 3, ovarian dysgenesis 7, ovarian dysgenesis 1, ovarian dysgenesis 9, ovarian dysgenesis 10, ovarian dysgenesis 8, ovarian dysgenesis 5, ovarian dysgenesis 6, ovarian dysgenesis 11

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

28 retrieved; paginated sample, class counts are floors:

7 benign, 6 pathogenic, 6 uncertain significance, 4 benign/likely benign, 3 conflicting classifications of pathogenicity, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11470	NM_005448.2(BMP15):c.704A>G (p.Tyr235Cys)	BMP15	Pathogenic	no assertion criteria provided
1685573	NM_005448.2(BMP15):c.413G>A (p.Arg138His)	BMP15	Pathogenic	criteria provided, single submitter
1685574	NM_005448.2(BMP15):c.617G>A (p.Arg206His)	BMP15	Pathogenic	criteria provided, single submitter
1685575	NM_005448.2(BMP15):c.661T>C (p.Trp221Arg)	BMP15	Pathogenic	criteria provided, single submitter
1685576	NM_005448.2(BMP15):c.727A>G (p.Ile243Val)	BMP15	Pathogenic	criteria provided, single submitter
973167	NM_005448.2(BMP15):c.-49_*34del (p.Met1fs)	BMP15	Pathogenic	no assertion criteria provided
973166	NM_005448.2(BMP15):c.462del (p.Trp155fs)	BMP15	Likely pathogenic	no assertion criteria provided
11471	NM_005448.2(BMP15):c.226C>T (p.Arg76Cys)	BMP15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
11472	NM_005448.2(BMP15):c.538G>A (p.Ala180Thr)	BMP15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
11474	NM_005448.2(BMP15):c.202C>T (p.Arg68Trp)	BMP15	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2439529	NM_005448.2(BMP15):c.731G>A (p.Arg244Gln)	BMP15	Uncertain significance	criteria provided, single submitter
2664021	NM_005448.2(BMP15):c.611G>A (p.Arg204Gln)	BMP15	Uncertain significance	no assertion criteria provided
3778898	NM_005448.2(BMP15):c.455T>C (p.Val152Ala)	BMP15	Uncertain significance	criteria provided, single submitter
913022	NM_005448.2(BMP15):c.811G>T (p.Gly271Cys)	BMP15	Uncertain significance	criteria provided, multiple submitters, no conflicts
913023	NM_005448.2(BMP15):c.920A>G (p.His307Arg)	BMP15	Uncertain significance	criteria provided, single submitter
973168	NM_005448.2(BMP15):c.985C>T (p.Arg329Cys)	BMP15	Uncertain significance	criteria provided, single submitter
136522	NM_005448.2(BMP15):c.-9C>G	BMP15	Benign	criteria provided, multiple submitters, no conflicts
136523	NM_005448.2(BMP15):c.308A>G (p.Asn103Ser)	BMP15	Benign	criteria provided, multiple submitters, no conflicts
259773	NM_005448.2(BMP15):c.*13G>A	BMP15	Benign	criteria provided, multiple submitters, no conflicts
259774	NM_005448.2(BMP15):c.13A>C (p.Ser5Arg)	BMP15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
259776	NM_005448.2(BMP15):c.819A>C (p.Ser273=)	BMP15	Benign	criteria provided, multiple submitters, no conflicts
259777	NM_005448.2(BMP15):c.852C>T (p.Ser284=)	BMP15	Benign	criteria provided, multiple submitters, no conflicts
368538	NM_005448.2(BMP15):c.443T>C (p.Leu148Pro)	BMP15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
368539	NM_005448.2(BMP15):c.581T>C (p.Phe194Ser)	BMP15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
368540	NM_005448.2(BMP15):c.598C>T (p.His200Tyr)	BMP15	Benign	criteria provided, single submitter
368541	NM_005448.2(BMP15):c.1011C>T (p.His337=)	BMP15	Benign	criteria provided, multiple submitters, no conflicts
914978	NM_005448.2(BMP15):c.162C>T (p.Gly54=)	BMP15	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
914979	NM_005448.2(BMP15):c.520C>T (p.Pro174Ser)	BMP15	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BMP15	Strong	X-linked	ovarian dysgenesis 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMP15	Orphanet:243	46,XX gonadal dysgenesis
BMP15	Orphanet:398987	Malignant teratoma of ovary

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMP15	HGNC:1068	ENSG00000130385	O95972	Bone morphogenetic protein 15	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP15	Bone morphogenetic protein 15	May be involved in follicular development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMP15	Other/Unknown	no		TGF-b_C, TGF-beta-like, TGFb_CS

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
pancreatic ductal cell	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP15	8		yes	secondary oocyte, oocyte, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMP15	1,566

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BMP15	O95972	72.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Post-translational protein phosphorylation	1	100.2×	0.023	BMP15
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.023	BMP15
Post-translational protein modification	1	19.2×	0.069	BMP15
Metabolism of proteins	1	12.4×	0.081	BMP15

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
female gamete generation	1	802.5×	0.001	BMP15
cell surface receptor protein serine/threonine kinase signaling pathway	1	732.7×	0.001	BMP15

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMP15	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BMP15

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.