Premature ovarian failure 19

disease

On this page

Also known as POF19

Summary

Premature ovarian failure 19 (MONDO:0030985) is a disease caused by HSF2BP (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: HSF2BP (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 19
Mondo ID	MONDO:0030985
OMIM	619245
DOID	DOID:0112278
UMLS	C5543229
MedGen	1779702
GARD	0025673
Is cancer (heuristic)	no

Also known as: POF19 · premature ovarian failure 19

Data availability: 4 ClinVar variants · 2 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 19

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:

2 likely pathogenic, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
228325	NM_017721.5(CC2D1A):c.748+1G>T	CC2D1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1224546	NM_007031.2(HSF2BP):c.557T>C (p.Leu186Pro)	HSF2BP	Likely pathogenic	criteria provided, single submitter
1224547	NM_007031.2(HSF2BP):c.382T>C (p.Cys128Arg)	HSF2BP	Likely pathogenic	criteria provided, single submitter
1047933	NM_007031.2(HSF2BP):c.500C>T (p.Ser167Leu)	HSF2BP	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
HSF2BP	Strong	Autosomal recessive	premature ovarian failure 19	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CC2D1A	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
HSF2BP	HGNC:5226	ENSG00000160207	O75031	Heat shock factor 2-binding protein	gencc,clinvar
CC2D1A	HGNC:30237	ENSG00000132024	Q6P1N0	Coiled-coil and C2 domain-containing protein 1A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HSF2BP	Heat shock factor 2-binding protein	Meiotic recombination factor component of recombination bridges involved in meiotic double-strand break repair.
CC2D1A	Coiled-coil and C2 domain-containing protein 1A	Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSF2BP	Other/Unknown	no		ARM-like, ARM-type_fold, HSF2BP
CC2D1A	Other/Unknown	no		C2_dom, CC2D1A/B_DM14, C2_domain_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
primordial germ cell in gonad	1
testis	1
cerebellar hemisphere	1
mucosa of transverse colon	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSF2BP	124	ubiquitous	yes	primordial germ cell in gonad, left testis, testis
CC2D1A	134	ubiquitous	marker	right hemisphere of cerebellum, mucosa of transverse colon, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSF2BP	1,882
CC2D1A	1,127

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HSF2BP	O75031	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CC2D1A	Q6P1N0	74.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apical dendrite arborization	1	8426.0×	9e-04	CC2D1A
negative regulation of snRNA transcription by RNA polymerase II	1	8426.0×	9e-04	CC2D1A
female meiosis I	1	936.2×	0.005	HSF2BP
regulation of respiratory gaseous exchange by nervous system process	1	648.1×	0.005	CC2D1A
double-strand break repair involved in meiotic recombination	1	648.1×	0.005	HSF2BP
male meiosis I	1	290.6×	0.009	HSF2BP
endosome organization	1	187.2×	0.011	CC2D1A
regulation of postsynapse assembly	1	172.0×	0.011	CC2D1A
long-term synaptic potentiation	1	140.4×	0.011	CC2D1A
social behavior	1	135.9×	0.011	CC2D1A
learning or memory	1	120.4×	0.011	CC2D1A
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.032	CC2D1A
transcription by RNA polymerase II	1	35.3×	0.032	HSF2BP
spermatogenesis	1	17.6×	0.060	HSF2BP
regulation of transcription by RNA polymerase II	1	5.8×	0.164	CC2D1A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
HSF2BP	0	0
CC2D1A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	HSF2BP, CC2D1A

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)
HSF2BP	0	—
CC2D1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: HSF2BP, CC2D1A