premature ovarian failure 2A

disease

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Also known as DIAPH2 primary ovarian failurePOF2Apremature ovarian failure 2A, X-linked dominantpremature ovarian failure type 2Aprimary ovarian failure caused by mutation in DIAPH2

Summary

premature ovarian failure 2A (MONDO:0010350) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

Cohort genes: 1
ClinVar variants: 7
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 2A
Mondo ID	MONDO:0010350
MeSH	C564498
OMIM	300511
DOID	DOID:0080858
UMLS	C1845293
MedGen	336902
GARD	0024719
Is cancer (heuristic)	no

Also known as: DIAPH2 primary ovarian failure · POF2A · premature ovarian failure 2A · premature ovarian failure 2A, X-linked dominant · premature ovarian failure type 2A · primary ovarian failure caused by mutation in DIAPH2

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

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 2A

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

7 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11622	t(X;12)(q21;p13)	DIAPH2	Pathogenic	no assertion criteria provided
2627053	NM_006729.5(DIAPH2):c.1586A>C (p.Glu529Ala)	DIAPH2	Uncertain significance	no assertion criteria provided
2627063	NM_006729.5(DIAPH2):c.2701G>A (p.Val901Ile)	DIAPH2	Uncertain significance	criteria provided, single submitter
3779240	NM_006729.5(DIAPH2):c.385A>G (p.Asn129Asp)	DIAPH2	Uncertain significance	criteria provided, single submitter
3779241	NM_006729.5(DIAPH2):c.742C>A (p.Gln248Lys)	DIAPH2	Uncertain significance	criteria provided, single submitter
3779569	NM_006729.5(DIAPH2):c.733-1G>T	DIAPH2	Uncertain significance	criteria provided, single submitter
790385	NM_006729.5(DIAPH2):c.247G>A (p.Ala83Thr)	DIAPH2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
DIAPH2	Limited	Unknown	premature ovarian failure 2A

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
DIAPH2	HGNC:2877	ENSG00000147202	O60879	Protein diaphanous homolog 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DIAPH2	Protein diaphanous homolog 2	Could be involved in oogenesis.

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)
DIAPH2	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like

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
bronchial epithelial cell	1
buccal mucosa cell	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DIAPH2	286	ubiquitous	marker	buccal mucosa cell, parietal pleura, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DIAPH2	1,769

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DIAPH2	O60879	76.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
RHOF GTPase cycle	1	259.6×	0.007	DIAPH2
RHOD GTPase cycle	1	203.9×	0.007	DIAPH2
RHO GTPases Activate Formins	1	77.7×	0.013	DIAPH2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
female gamete generation	1	802.5×	0.003	DIAPH2
actin filament polymerization	1	481.5×	0.003	DIAPH2
oogenesis	1	383.0×	0.003	DIAPH2

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
DIAPH2	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	DIAPH2

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)
DIAPH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials

Cohort genes: DIAPH2