Premature ovarian failure 17

Summary

Premature ovarian failure 17 (MONDO:0030870) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 17
Mondo ID	MONDO:0030870
OMIM	619146
DOID	DOID:0080874
UMLS	C5436889
MedGen	1748767
GARD	0025647
Is cancer (heuristic)	no

Also known as: POF17 · premature ovarian failure 17

Data availability: 12 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 17

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 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 23, 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

12 retrieved; paginated sample, class counts are floors:

6 conflicting classifications of pathogenicity, 6 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
127954	NM_005431.2(XRCC2):c.283A>G (p.Ile95Val)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127963	NM_005431.2(XRCC2):c.773G>A (p.Arg258His)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420029	NM_005431.2(XRCC2):c.651_652del (p.Cys217_Asp218delinsTer)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420244	NM_005431.2(XRCC2):c.350dup (p.Leu117fs)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
486729	NM_005431.2(XRCC2):c.190C>T (p.Arg64Ter)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
584725	NM_005431.2(XRCC2):c.581C>T (p.Thr194Met)	XRCC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127962	NM_005431.2(XRCC2):c.667T>C (p.Tyr223His)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594438	NM_005431.2(XRCC2):c.563G>T (p.Arg188Leu)	XRCC2	Uncertain significance	criteria provided, single submitter
486728	NM_005431.2(XRCC2):c.659A>T (p.Asp220Val)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
824871	NM_005431.2(XRCC2):c.440T>A (p.Ile147Asn)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
827540	NM_005431.2(XRCC2):c.825T>G (p.Ser275Arg)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
992194	NM_005431.2(XRCC2):c.41T>C (p.Leu14Pro)	XRCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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
XRCC2	Limited	Unknown	spermatogenic failure 50	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XRCC2	Orphanet:227535	Hereditary breast cancer
XRCC2	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
XRCC2	Orphanet:84	Fanconi anemia

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
XRCC2	HGNC:12829	ENSG00000196584	O43543	DNA repair protein XRCC2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XRCC2	DNA repair protein XRCC2	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions.

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)
XRCC2	Other/Unknown	no		Rad51_C, RecA_ATP-bd, P-loop_NTPase

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
buccal mucosa cell	1
lateral globus pallidus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XRCC2	283	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XRCC2	1,314

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XRCC2	O43543	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Impaired BRCA2 binding to PALB2	1	456.8×	0.004	XRCC2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.004	XRCC2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.004	XRCC2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.004	XRCC2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.004	XRCC2
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.004	XRCC2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.004	XRCC2
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.004	XRCC2
HDR through Homologous Recombination (HRR)	1	190.3×	0.005	XRCC2

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
regulation of fibroblast apoptotic process	1	5617.3×	0.002	XRCC2
DNA strand invasion	1	4213.0×	0.002	XRCC2
response to X-ray	1	887.0×	0.005	XRCC2
response to gamma radiation	1	581.1×	0.005	XRCC2
positive regulation of neurogenesis	1	581.1×	0.005	XRCC2
somitogenesis	1	374.5×	0.006	XRCC2
centrosome cycle	1	337.0×	0.006	XRCC2
meiotic cell cycle	1	244.2×	0.008	XRCC2
neurogenesis	1	208.1×	0.008	XRCC2
double-strand break repair via homologous recombination	1	156.0×	0.009	XRCC2
multicellular organism growth	1	137.0×	0.009	XRCC2
mitotic cell cycle	1	133.8×	0.009	XRCC2
negative regulation of neuron apoptotic process	1	110.9×	0.010	XRCC2
in utero embryonic development	1	72.0×	0.015	XRCC2
DNA repair	1	63.8×	0.016	XRCC2

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
XRCC2	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	XRCC2

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)
XRCC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.