Premature ovarian failure 20

disease

On this page

Also known as POF20

Summary

Premature ovarian failure 20 (MONDO:0030975) is a disease caused by MSH4 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: MSH4 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 20
Mondo ID	MONDO:0030975
OMIM	619938
UMLS	C5677011
MedGen	1808256
GARD	0025670
Is cancer (heuristic)	no

Also known as: POF20 · premature ovarian failure 20

Data availability: 8 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 20

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

8 retrieved; paginated sample, class counts are floors:

5 benign, 1 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1693499	NM_002440.4(MSH4):c.2355+1G>A	MSH4	Pathogenic	no assertion criteria provided
869115	NM_002440.4(MSH4):c.2261C>T (p.Ser754Leu)	MSH4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
992889	NM_002440.4(MSH4):c.2198C>A (p.Ser733Ter)	MSH4	Likely pathogenic	criteria provided, single submitter
2585667	NM_002440.4(MSH4):c.289G>A (p.Ala97Thr)	MSH4	Benign	criteria provided, single submitter
2585668	NM_002440.4(MSH4):c.1540+8C>A	MSH4	Benign	criteria provided, single submitter
2585669	NM_002440.4(MSH4):c.1569T>C (p.Tyr523=)	MSH4	Benign	criteria provided, single submitter
2585670	NM_002440.4(MSH4):c.1575A>T (p.Leu525=)	MSH4	Benign	criteria provided, single submitter
2585671	NM_002440.4(MSH4):c.1782-11_1782-10insAT	MSH4	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
MSH4	Strong	Autosomal recessive	premature ovarian failure 20	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSH4	Orphanet:243	46,XX gonadal dysgenesis

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
MSH4	HGNC:7327	ENSG00000057468	O15457	MutS protein homolog 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSH4	MutS protein homolog 4	Involved in meiotic recombination.

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)
MSH4	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS_core, DNA_mmatch_repair_MutS_con_dom

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
primordial germ cell in gonad	1
right coronary artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSH4	145	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSH4	1,647

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MSH4	O15457	75.12

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
Meiosis	1	285.5×	0.010	MSH4
Reproduction	1	190.3×	0.010	MSH4
Meiotic recombination	1	129.8×	0.010	MSH4
Cell Cycle	1	36.0×	0.028	MSH4

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
female gamete generation	1	802.5×	0.003	MSH4
mismatch repair	1	648.1×	0.003	MSH4
homologous chromosome pairing at meiosis	1	601.9×	0.003	MSH4
reciprocal meiotic recombination	1	561.7×	0.003	MSH4
ovarian follicle development	1	391.9×	0.003	MSH4
spermatogenesis	1	35.2×	0.028	MSH4

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
MSH4	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	MSH4

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)
MSH4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: MSH4