SMAD7
Chr 18SMAD family member 7
Also known as: CRCS3, MADH7, MADH8
SMAD7 encodes a nuclear protein that antagonizes TGF-beta signaling by binding to TGF-beta receptors and preventing SMAD2 access, while also recruiting SMURF2 to promote receptor degradation. Mutations cause susceptibility to colorectal cancer type 3 with autosomal inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.507), suggesting some intolerance to complete protein loss.
Primary Disease Associations & Inheritance
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
124 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 38 | 0 | 38 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 56 | 7 | 1 | 64 |
Likely Benign | 0 | 5 | 4 | 5 | 14 |
Benign | 0 | 1 | 0 | 4 | 5 |
| Total | 0 | 62 | 50 | 10 | 122 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SMAD7 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools