Premature ovarian failure: genes and variants
Premature ovarian failure is linked to 4 analyzed proteins (NOS3, CHEK2, FMR1 and XRCC2). 3 DNA variants are known to cause it; 29 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: premature ovarian failure 1; premature ovarian failure 17
Genes linked to Premature ovarian failure
NOS3: Nitric oxide synthase 3
It generates nitric oxide in vascular endothelium, promoting smooth-muscle relaxation, inhibiting platelet activation, and supporting vascular homeostasis. Reduced activity contributes to endothelial dysfunction, while common genetic variation has modest effects on cardiovascular traits.
2 disease-causing and 0 uncertain variants in NOS3 are linked to Premature ovarian failure.
CHEK2: Serine/threonine-protein kinase Chk2
It propagates DNA-damage checkpoint signals to proteins controlling cell-cycle arrest, repair, and apoptosis. Germline loss-of-function variants confer moderate cancer susceptibility, especially for breast cancer, while risk estimates depend on the specific allele and family context.
1 disease-causing and 0 uncertain variants in CHEK2 are linked to Premature ovarian failure.
FMR1: Fragile X messenger ribonucleoprotein 1
Its FMRP product binds neuronal RNAs and regulates their transport and local translation at synapses. Full CGG-repeat expansion silences the gene and causes fragile X syndrome, while premutation alleles can cause tremor-ataxia syndrome or primary ovarian insufficiency.
0 disease-causing and 2 uncertain variants in FMR1 are linked to Premature ovarian failure.
XRCC2: DNA repair protein XRCC2
It acts with other RAD51 paralogs to assemble and stabilize homologous-recombination repair machinery at DNA double-strand breaks. Biallelic loss-of-function variants can cause Fanconi-anemia-like chromosome-instability disease, while heterozygous cancer-risk associations are less certain.
0 disease-causing and 9 uncertain variants in XRCC2 are linked to Premature ovarian failure.
Weakly linked (only a few uncertain records): RYR3, BRD3, C3, CHD7, CYP17A1, CYP19A1, FANCC, GALT and 9 more.
Known disease-causing variants in Premature ovarian failure
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CHEK2 Y390S | 390 | Protein kinase | Disease-causing (★★) |
| NOS3 E169K | 169 | Interaction with NOSIP | Disease-causing (★) |
| NOS3 P58S | 58 | Disease-causing (★) |
Same protein, different disease
- CHEK2-related cancer predisposition is also caused by CHEK2 variants; they fall mostly in different places as the Premature ovarian failure variants (3 disease-causing).
- Familial cancer of breast is also caused by CHEK2 variants; they fall mostly in different places as the Premature ovarian failure variants (3 disease-causing).
Diseases related to Premature ovarian failure
- Li-Fraumeni syndrome, also linked to CHEK2
- Familial cancer of breast, also linked to CHEK2
- Fanconi anemia, also linked to XRCC2
- Colorectal cancer, also linked to CHEK2
- Gastric cancer, also linked to CHEK2
- Hereditary nonpolyposis colon cancer, also linked to CHEK2
- Hereditary breast ovarian cancer syndrome, also linked to CHEK2
- Prostate cancer, also linked to CHEK2
- Breast and/or ovarian cancer, also linked to CHEK2
- Bone osteosarcoma, also linked to CHEK2
- Spermatogenic failure 72, also linked to XRCC2
- CHEK2-related cancer predisposition, also linked to CHEK2
Frequently asked questions
Which genes are linked to Premature ovarian failure?
In CATVariant, Premature ovarian failure is linked to 4 analyzed proteins: NOS3 (Nitric oxide synthase 3), CHEK2 (Serine/threonine-protein kinase Chk2), FMR1 (Fragile X messenger ribonucleoprotein 1) and XRCC2 (DNA repair protein XRCC2).
How many genetic variants are linked to Premature ovarian failure?
37 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 29 are of uncertain significance or have conflicting reports.
Which uncertain variants in Premature ovarian failure look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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