Premature ovarian failure 23

Summary

Premature ovarian failure 23 (MONDO:0958035) is a disease caused by MEIOB (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MEIOB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 23
Mondo ID	MONDO:0958035
OMIM	620686
UMLS	C5882747
MedGen	1845723
GARD	0026916
Is cancer (heuristic)	no

Data availability: 4 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 23

Related subtypes (40): blepharophimosis, ptosis, and epicanthus inversus syndrome, congenital lipoid adrenal hyperplasia due to STAR deficency, ataxia telangiectasia, classic galactosemia, 46 XX gonadal dysgenesis, premature ovarian failure 2A, premature ovarian failure 2B, premature ovarian failure 1, Satoyoshi syndrome, premature ovarian failure 3, osteosclerosis-ichthyosis-premature ovarian failure syndrome, premature ovarian failure 5, premature ovarian failure 6, premature ovarian failure 7, aromatase deficiency, premature ovarian failure 8, premature ovarian failure 9, 46,XX ovarian dysgenesis-short stature syndrome, premature ovarian failure 11, premature ovarian failure 12, Perrault syndrome, trisomy X, Turner syndrome, tetrasomy X, X small rings, premature ovarian failure 17, premature ovarian failure 18, premature ovarian failure 20, premature ovarian failure 19, premature ovarian failure 16, premature ovarian failure 13, premature ovarian failure 10, premature ovarian failure 14, premature ovarian failure 15, premature ovarian failure 4, premature ovarian failure 21, premature ovarian failure 22, premature ovarian failure 24, premature ovarian failure 25, premature ovarian failure 26

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2691779	NM_001163560.3(MEIOB):c.1218G>A (p.Thr406=)	FAHD1	Pathogenic	no assertion criteria provided
2045761	NM_001163560.3(MEIOB):c.814C>T (p.Arg272Ter)	MEIOB	Pathogenic	criteria provided, single submitter
2691780	NM_001163560.3(MEIOB):c.683-1G>A	MEIOB	Pathogenic	no assertion criteria provided
2691781	NM_001163560.3(MEIOB):c.1072_1073del (p.Met358fs)	FAHD1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
MEIOB	Strong	Autosomal recessive	spermatogenic failure 22	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MEIOB	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MEIOB	HGNC:28569	ENSG00000162039	Q8N635	Meiosis-specific with OB domain-containing protein	gencc,clinvar
FAHD1	HGNC:14169	ENSG00000180185	Q6P587	Oxaloacetate tautomerase FAHD1, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MEIOB	Meiosis-specific with OB domain-containing protein	Single-stranded DNA-binding protein required for homologous recombination in meiosis I.
FAHD1	Oxaloacetate tautomerase FAHD1, mitochondrial	Tautomerase that converts enol-oxaloacetate, a strong inhibitor of succinate dehydrogenase, to the physiological keto form of oxaloacetate.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MEIOB	Other/Unknown	no		NA-bd_OB-fold, MEIOB, OB_MEIOB_N
FAHD1	Enzyme (other)	yes	3.7.1.5	Fumarylacetoacetase-like_C, Fumarylacetoacetase_C_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
primordial germ cell in gonad	1
right testis	1
ileal mucosa	1
kidney epithelium	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MEIOB	154	broad	marker	right testis, left testis, primordial germ cell in gonad
FAHD1	255	ubiquitous	marker	kidney epithelium, ileal mucosa, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEIOB	2,070
FAHD1	1,880

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FAHD1	Q6P587	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MEIOB	Q8N635	81.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Pyruvate metabolism	1	407.9×	0.002	FAHD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
female meiosis I	1	936.2×	0.005	MEIOB
oxaloacetate metabolic process	1	766.0×	0.005	FAHD1
resolution of meiotic recombination intermediates	1	468.1×	0.005	MEIOB
homologous chromosome pairing at meiosis	1	300.9×	0.005	MEIOB
male meiosis I	1	290.6×	0.005	MEIOB
male meiotic nuclear division	1	271.8×	0.005	MEIOB
fertilization	1	156.0×	0.007	MEIOB
double-strand break repair via homologous recombination	1	78.0×	0.013	MEIOB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEIOB	0	0
FAHD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FAHD1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FAHD1	3.7.1.5, 4.1.1.112	acylpyruvate hydrolase, oxaloacetate decarboxylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	FAHD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MEIOB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MEIOB	0	—
FAHD1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.