Premature ovarian failure 14

disease

On this page

Also known as GDF9-related primary ovarian insufficiencyPOF14

Summary

Premature ovarian failure 14 (MONDO:0044777) is a disease caused by GDF9 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

Causal gene: GDF9 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 9
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 14
Mondo ID	MONDO:0044777
OMIM	618014
DOID	DOID:0080871
UMLS	C4693941
MedGen	1646133
GARD	0025909
Is cancer (heuristic)	no

Also known as: GDF9-related primary ovarian insufficiency · POF14 · premature ovarian failure 14

Data availability: 9 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited primary ovarian failure › premature ovarian failure 14

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

9 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3255469	NM_005260.7(GDF9):c.1121C>T (p.Pro374Leu)	GDF9	Pathogenic	no assertion criteria provided
3255470	NM_005260.7(GDF9):c.794T>G (p.Leu265Ter)	GDF9	Pathogenic	no assertion criteria provided
1299519	NM_005260.7(GDF9):c.1364A>C (p.Ter455Ser)	GDF9	Likely pathogenic	criteria provided, single submitter
3068062	NM_005260.7(GDF9):c.759_762del (p.Phe254fs)	GDF9	Likely pathogenic	criteria provided, single submitter
545504	NM_005260.7(GDF9):c.783del (p.Ser262fs)	GDF9	Likely pathogenic	criteria provided, single submitter
3383109	NM_005260.7(GDF9):c.1275C>A (p.Ser425Arg)	GDF9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1256000	NM_005260.7(GDF9):c.1283G>C (p.Ser428Thr)	GDF9	Uncertain significance	criteria provided, single submitter
1804884	NM_005260.7(GDF9):c.604C>T (p.Gln202Ter)	GDF9	Uncertain significance	criteria provided, single submitter
3780856	NM_005260.7(GDF9):c.-1088A>G	GDF9	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
GDF9	Strong	Autosomal recessive	premature ovarian failure 14	3

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
GDF9	HGNC:4224	ENSG00000164404	O60383	Growth/differentiation factor 9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GDF9	Growth/differentiation factor 9	Required for ovarian folliculogenesis.

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)
GDF9	Other/Unknown	no		TGF-b_C, TGF-beta-like, Growth_differentiation_fac-9_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GDF9	168	tissue_specific	marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GDF9	1,340

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GDF9	O60383	66.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
regulation of progesterone secretion	1	16852.0×	4e-04	GDF9
oocyte growth	1	4213.0×	8e-04	GDF9
female gamete generation	1	802.5×	0.002	GDF9
cell surface receptor protein serine/threonine kinase signaling pathway	1	732.7×	0.002	GDF9
transforming growth factor beta receptor signaling pathway	1	159.0×	0.008	GDF9
negative regulation of cell growth	1	144.0×	0.008	GDF9
positive regulation of cell population proliferation	1	33.6×	0.030	GDF9

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
GDF9	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	GDF9

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)
GDF9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation

Cohort genes: GDF9