Familial colorectal cancer: genes and variants
Familial colorectal cancer is linked to 4 analyzed proteins (MUTYH, POLE, ATM and POLD1). 1 DNA variants are known to cause it; 25 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: familial colorectal cancer type X
Genes linked to Familial colorectal cancer
MUTYH: Adenine DNA glycosylase
It removes adenines incorrectly paired with oxidized guanine, preventing characteristic G:C-to-T:A mutations during base-excision repair. Biallelic loss-of-function variants cause MUTYH-associated polyposis and substantially increase colorectal-cancer risk.
1 disease-causing and 6 uncertain variants in MUTYH are linked to Familial colorectal cancer.
POLE: DNA polymerase epsilon catalytic subunit A
It performs leading-strand DNA synthesis and proofreads newly incorporated bases during replication. Germline exonuclease-domain variants cause polymerase-proofreading-associated polyposis, while somatic proofreading defects create ultramutated tumors with distinctive mutation signatures.
0 disease-causing and 2 uncertain variants in POLE are linked to Familial colorectal cancer.
ATM: Serine-protein kinase ATM
It is activated by DNA double-strand breaks and coordinates checkpoint arrest, repair, and apoptosis through phosphorylation of numerous targets. Biallelic loss causes ataxia-telangiectasia, while heterozygous pathogenic variants increase susceptibility to several cancers.
0 disease-causing and 2 uncertain variants in ATM are linked to Familial colorectal cancer.
POLD1: DNA polymerase delta catalytic subunit
It performs much of lagging-strand DNA synthesis and proofreads newly replicated DNA through its exonuclease activity. Germline proofreading-domain variants cause polymerase-proofreading-associated polyposis and cancer predisposition, while other variants can produce developmental progeroid syndromes.
0 disease-causing and 13 uncertain variants in POLD1 are linked to Familial colorectal cancer.
Weakly linked (only a few uncertain records): CHEK2.
Known disease-causing variants in Familial colorectal cancer
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MUTYH R179H | 179 | Disease-causing (★★) |
Same protein, different disease
- Familial adenomatous polyposis is also caused by MUTYH variants; they fall mostly in different places as the Familial colorectal cancer variants (27 disease-causing).
- Gastric cancer is also caused by MUTYH variants; they fall mostly in different places as the Familial colorectal cancer variants (11 disease-causing).
Diseases related to Familial colorectal cancer
- Colorectal cancer, also linked to ATM, MUTYH, POLD1 and POLE
- Ovarian cancer, also linked to ATM, POLD1 and POLE
- Acute myeloid leukemia, also linked to POLD1 and POLE
- Gastric cancer, also linked to ATM and MUTYH
- Non-small cell lung carcinoma, also linked to POLD1 and POLE
- Myelodysplastic syndrome, also linked to POLD1 and POLE
- Autosomal dominant nonsyndromic hearing loss, also linked to POLE
- Familial adenomatous polyposis, also linked to MUTYH
- Familial cancer of breast, also linked to ATM
- Hereditary breast ovarian cancer syndrome, also linked to ATM
- Pilomatrixoma, also linked to MUTYH
- Familial pancreatic carcinoma, also linked to ATM
Frequently asked questions
Which genes are linked to Familial colorectal cancer?
In CATVariant, Familial colorectal cancer is linked to 4 analyzed proteins: MUTYH (Adenine DNA glycosylase), POLE (DNA polymerase epsilon catalytic subunit A), ATM (Serine-protein kinase ATM) and POLD1 (DNA polymerase delta catalytic subunit).
How many genetic variants are linked to Familial colorectal cancer?
27 variants: 1 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 25 are of uncertain significance or have conflicting reports.
Which uncertain variants in Familial colorectal cancer 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center