SMAD7

Chr 18

SMAD family member 7

Also known as: CRCS3, MADH7, MADH8

NCBI Gene: 4092ENSG00000101665UniProt: O15105OMIM: 602932

The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Colorectal cancer, susceptibility to, 3}MIM #612229
UniProtColorectal cancer 3

Clinical highlights

Gene-disease validity (ClinGen)
congenital heart disease · ADLimitednot for standalone diagnostic reporting
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
2
Active trials
233
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.51
LOEUF
LOF
Mechanism· predicted
📖
GeneReview available — SMAD7
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.51LOEUF
pLI 0.549
Z-score 2.91
OE 0.20 (0.09–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.65Z-score
OE missense 0.69 (0.60–0.79)
154 obs / 223.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.09–0.51)
0≤0.351.4
Missense OE?0.69 (0.60–0.79)
0≤0.61.4
Synonymous OE?1.24
0≤1.21.6
LoF obs/exp: 3 / 15.3Missense obs/exp: 154 / 223.5Syn Z: -1.97

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients