Premature ovarian failure 9

disease

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Also known as HFM1 primary ovarian failurePof9premature ovarian failure type 9primary ovarian failure caused by mutation in HFM1

Summary

Premature ovarian failure 9 (MONDO:0014322) is a disease caused by HFM1 (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

Causal gene: HFM1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 16
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 9
Mondo ID	MONDO:0014322
OMIM	615724
DOID	DOID:0080866
UMLS	C3810376
MedGen	816706
GARD	0024986
Is cancer (heuristic)	no

Also known as: HFM1 primary ovarian failure · Pof9 · premature ovarian failure 9 · premature ovarian failure type 9 · primary ovarian failure caused by mutation in HFM1

Data availability: 16 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 9

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

16 retrieved; paginated sample, class counts are floors:

7 likely pathogenic, 5 pathogenic, 3 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
126428	NM_001017975.6(HFM1):c.1686G>C (p.Arg562Ser)	HFM1	Pathogenic	no assertion criteria provided
126429	NM_001017975.6(HFM1):c.2651T>G (p.Ile884Ser)	HFM1	Pathogenic	no assertion criteria provided
126430	NM_001017975.6(HFM1):c.2206G>A (p.Gly736Ser)	HFM1	Pathogenic	no assertion criteria provided
126431	NM_001017975.6(HFM1):c.3929_3930delinsG (p.Pro1310fs)	HFM1	Pathogenic	no assertion criteria provided
996213	NM_001017975.6(HFM1):c.1905T>A (p.Tyr635Ter)	HFM1	Pathogenic	no assertion criteria provided
1214012	NM_001017975.6(HFM1):c.2410G>T (p.Glu804Ter)	HFM1	Likely pathogenic	no assertion criteria provided
1332985	NM_001017975.6(HFM1):c.2562_2563del (p.Glu856fs)	HFM1	Likely pathogenic	criteria provided, single submitter
2440702	NM_001017975.6(HFM1):c.1159-3_1159-2del	HFM1	Likely pathogenic	criteria provided, single submitter
2627515	NM_001017975.6(HFM1):c.2T>C (p.Met1Thr)	HFM1	Likely pathogenic	criteria provided, single submitter
3779730	NM_001017975.6(HFM1):c.873+2T>C	HFM1	Likely pathogenic	criteria provided, single submitter
3779731	NM_001017975.6(HFM1):c.3057_3058del (p.Arg1021fs)	HFM1	Likely pathogenic	criteria provided, single submitter
4845705	NM_001017975.6(HFM1):c.3421C>T (p.Arg1141Ter)	HFM1	Likely pathogenic	criteria provided, single submitter
2498407	NM_001017975.6(HFM1):c.3470G>A (p.Cys1157Tyr)	HFM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779729	NM_001017975.6(HFM1):c.3032del (p.Ile1010_Leu1011insTer)	HFM1	Uncertain significance	criteria provided, single submitter
3893177	NM_001017975.6(HFM1):c.3047_3049dup (p.Gln1016_Leu1017insGln)	HFM1	Uncertain significance	criteria provided, single submitter
561186	NM_001017975.6(HFM1):c.4061del (p.Pro1354fs)	HFM1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
HFM1	Strong	Autosomal recessive	premature ovarian failure 9	4

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
HFM1	HGNC:20193	ENSG00000162669	A2PYH4	Probable ATP-dependent DNA helicase HFM1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HFM1	Probable ATP-dependent DNA helicase HFM1	Required for crossover formation and complete synapsis of homologous chromosomes during meiosis.

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)
HFM1	Other/Unknown	no		Helicase_C-like, Sec63-dom, DEAD/DEAH_box_helicase_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
pituitary gland	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HFM1	157	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HFM1	1,768

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HFM1	A2PYH4	65.49

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
resolution of meiotic recombination intermediates	1	936.2×	0.001	HFM1

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
HFM1	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	HFM1

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)
HFM1	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: HFM1