Colon carcinoma: genes and variants
Explore variant evidence for Colon carcinoma across 14 analyzed proteins (FGFR3, PPARG, CTNNB1, PIK3CA, FLCN and 9 more). Linked ClinVar records include 10 pathogenic or likely pathogenic variants, 4 variants of uncertain significance and 2 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Colon carcinoma
FGFR3: Fibroblast growth factor receptor 3
It normally restrains growth-plate chondrocyte proliferation while regulating multiple developmental pathways. Activating germline variants cause achondroplasia and related skeletal dysplasias, while somatic activating alterations are common in bladder cancer and some other tumors.
3 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in FGFR3 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
PPARG: Peroxisome proliferator-activated receptor gamma
It drives adipocyte differentiation, lipid storage, and insulin-sensitive metabolic programs in response to endogenous lipids and thiazolidinedione drugs. Dominant-negative variants cause familial partial lipodystrophy type 3 with severe insulin resistance and dyslipidemia.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PPARG have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
CTNNB1: Catenin beta-1
It links cadherins to the cytoskeleton at adherens junctions and, when stabilized by Wnt signaling, enters the nucleus to regulate transcription. Activating somatic variants drive many cancers, while germline loss-of-function variants cause CTNNB1 neurodevelopmental disorder.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CTNNB1 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
PIK3CA: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Its p110-alpha catalytic activity generates PIP3 and activates AKT-dependent growth, survival, and metabolic signaling downstream of many receptors. Activating variants are frequent cancer drivers and, when present mosaically during development, can cause PIK3CA-related overgrowth spectrum.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PIK3CA have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
FLCN: Folliculin
It couples lysosomal nutrient sensing to AMPK, mTOR, and related pathways and helps regulate cell growth and metabolism. Germline loss-of-function variants cause Birt-Hogg-Dube syndrome with fibrofolliculomas, pulmonary cysts, pneumothorax, and renal-tumor predisposition.
0 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in FLCN have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
MLH1: DNA mismatch repair protein Mlh1
The protein partners with PMS2 to form MutL alpha, a core complex in post-replicative DNA mismatch repair. By helping correct copying errors in DNA, MLH1 protects genome stability, and inherited MLH1 variants are a major cause of Lynch syndrome.
0 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in MLH1 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
APC: Adenomatous polyposis coli protein
A tumor-suppressor protein that promotes the removal of beta-catenin and helps keep Wnt signaling under control. It also organizes microtubules and actin in the cell, and inherited APC disruption is strongly associated with familial adenomatous polyposis and colorectal tumor risk.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in APC have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
MSH2: DNA mismatch repair protein Msh2
The protein forms mismatch-recognition complexes with MSH6 or MSH3 that detect base mismatches and insertion-deletion loops in DNA. This first step of mismatch repair helps preserve genome integrity, and inherited MSH2 variants are associated with Lynch syndrome.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in MSH2 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
MSH6: DNA mismatch repair protein Msh6
Together with MSH2, it recognizes single-base mismatches and small insertion-deletion loops during DNA replication and initiates mismatch repair. Germline loss-of-function variants cause Lynch syndrome, while biallelic variants can cause constitutional mismatch-repair deficiency.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in MSH6 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
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.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in MUTYH have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
PMS2: Mismatch repair endonuclease PMS2
Together with MLH1, it provides endonuclease activity needed to complete DNA mismatch repair after replication errors are recognized. Germline loss-of-function variants cause Lynch syndrome, while biallelic variants cause constitutional mismatch-repair deficiency.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PMS2 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
BRAF: Serine/threonine-protein kinase B-raf
It relays activated RAS signals through MEK and ERK to control proliferation, differentiation, and survival. Activating variants, especially V600E, drive melanoma and several other cancers and create sensitivity to pathway-directed therapies.
2 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in BRAF have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
EP300: Histone acetyltransferase p300
It acetylates histones and transcription factors and acts as a central coactivator for developmental and stress-responsive transcription. Germline loss-of-function variants cause Rubinstein-Taybi syndrome type 2, while acquired alterations occur in several cancers.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in EP300 have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
DCC: Netrin receptor DCC
It guides developing axons in response to netrin signals and helps establish long-range neural connections across the midline. Heterozygous pathogenic variants can cause congenital mirror movements, while biallelic or severe variants can produce complex neurodevelopmental syndromes.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in DCC have source records linked to Colon carcinoma. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): BUB1B, AKT1, BAX, BCL10, MLH3 and PALB2.
ClinVar pathogenic and likely pathogenic variants linked to Colon carcinoma
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FGFR3 R248C | 248 | Extracellular | Pathogenic / likely pathogenic (★★★★) |
| FGFR3 N540K | 540 | Protein kinase | Pathogenic / likely pathogenic (★★) |
| PIK3CA H1047Y | 1047 | PI3K/PI4K catalytic | Pathogenic / likely pathogenic (★★) |
| BRAF R462I | 462 | Protein kinase | Pathogenic / likely pathogenic |
| BRAF I463S | 463 | Protein kinase | Pathogenic / likely pathogenic |
| FGFR3 E322K | 322 | Ig-like C2-type 3 | Pathogenic / likely pathogenic |
| PPARG Q314P | 314 | NR LBD | Pathogenic / likely pathogenic |
| CTNNB1 S33Y | 33 | Pathogenic / likely pathogenic | |
| DCC P1375H | 1375 | Cytoplasmic | Pathogenic / likely pathogenic |
| EP300 P2221Q | 2221 | Interaction with NCOA2 | Pathogenic / likely pathogenic |
Which prediction tools work for Colon carcinoma
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- AlphaMissense: 80 out of 100
- EVE: 77 out of 100
- PolyPhen-2: 70 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 68 out of 100
- MutPred2: 67 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 65 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 50 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- FGFR3-related chondrodysplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Colon carcinoma variants (20 pathogenic / likely pathogenic).
- Hypochondroplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Colon carcinoma variants (15 pathogenic / likely pathogenic).
- Achondroplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Colon carcinoma variants (9 pathogenic / likely pathogenic).
- Thanatophoric dysplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Colon carcinoma variants (8 pathogenic / likely pathogenic).
- Severe achondroplasia - developmental delay - acanthosis nigricans also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Colon carcinoma variants (5 pathogenic / likely pathogenic).
- RASopathy also has ClinVar records linked to BRAF variants; they fall mostly in different places as the Colon carcinoma variants (36 pathogenic / likely pathogenic).
- Cardio-facio-cutaneous syndrome also has ClinVar records linked to BRAF variants; they fall mostly in different places as the Colon carcinoma variants (26 pathogenic / likely pathogenic).
- Cardiofaciocutaneous syndrome also has ClinVar records linked to BRAF variants; they fall mostly in different places as the Colon carcinoma variants (17 pathogenic / likely pathogenic).
- Noonan syndrome also has ClinVar records linked to BRAF variants; they fall mostly in different places as the Colon carcinoma variants (11 pathogenic / likely pathogenic).
- Noonan syndrome and Noonan-related syndrome also has ClinVar records linked to BRAF variants; they fall mostly in different places as the Colon carcinoma variants (10 pathogenic / likely pathogenic).
- PIK3CA related overgrowth syndrome also has ClinVar records linked to PIK3CA variants; they fall mostly in different places as the Colon carcinoma variants (30 pathogenic / likely pathogenic).
- Cowden disease also has ClinVar records linked to PIK3CA variants; they fall mostly in different places as the Colon carcinoma variants (23 pathogenic / likely pathogenic).
- Megalencephaly-capillary malformation-polymicrogyria syndrome also has ClinVar records linked to PIK3CA variants; they fall mostly in different places as the Colon carcinoma variants (22 pathogenic / likely pathogenic).
- Ovarian neoplasm also has ClinVar records linked to PIK3CA variants; they fall mostly in different places as the Colon carcinoma variants (5 pathogenic / likely pathogenic).
- PIK3CA constitutional syndrome also has ClinVar records linked to PIK3CA variants; they fall partly in the same places as the Colon carcinoma variants (4 pathogenic / likely pathogenic).
- Pilomatrixoma also has ClinVar records linked to CTNNB1 variants; they fall partly in the same places as the Colon carcinoma variants (8 pathogenic / likely pathogenic).
- Severe intellectual disability-progressive spastic diplegia syndrome also has ClinVar records linked to CTNNB1 variants; they fall mostly in different places as the Colon carcinoma variants (5 pathogenic / likely pathogenic).
- Medulloblastoma also has ClinVar records linked to CTNNB1 variants; they fall in the same places as the Colon carcinoma variants (4 pathogenic / likely pathogenic).
- Rubinstein-Taybi syndrome due to EP300 haploinsufficiency also has ClinVar records linked to EP300 variants; they fall mostly in different places as the Colon carcinoma variants (17 pathogenic / likely pathogenic).
- Menke-Hennekam syndrome also has ClinVar records linked to EP300 variants; they fall mostly in different places as the Colon carcinoma variants (4 pathogenic / likely pathogenic).
Diseases related to Colon carcinoma
- Colorectal cancer, also linked to APC, BRAF, CTNNB1, EP300 and 7 more
- Ovarian cancer, also linked to APC, CTNNB1, FLCN, MLH1 and 3 more
- Gastric cancer, also linked to APC, MLH1, MSH6, MUTYH and 2 more
- Endometrial carcinoma, also linked to MLH1, MSH2, MSH6, PIK3CA and 1 more
- Lynch syndrome, also linked to MLH1, MSH2, MSH6 and PMS2
- Hereditary nonpolyposis colorectal neoplasms, also linked to MLH1, MSH2, MSH6 and PMS2
- Urinary bladder cancer, also linked to CTNNB1, EP300, FGFR3 and PIK3CA
- Hereditary nonpolyposis colon cancer, also linked to MLH1, MSH2, MSH6 and PMS2
- Mismatch repair cancer syndrome, also linked to MLH1, MSH2, MSH6 and PMS2
- Hepatocellular carcinoma, also linked to APC, BRAF, CTNNB1 and PIK3CA
- Breast and/or ovarian cancer, also linked to MLH1, MSH2, MSH6 and PMS2
- Noonan syndrome, also linked to BRAF and PIK3CA
Frequently asked questions
Which genes have records linked to Colon carcinoma?
This view contains 14 analyzed proteins: FGFR3, PPARG, CTNNB1, PIK3CA, FLCN and 9 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 10 pathogenic or likely pathogenic variants, 4 variants of uncertain significance and 2 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 25 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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