TFF3
Chr 21trefoil factor 3
Also known as: ITF, P1B, TFI
TFF3 encodes trefoil factor 3, a secretory protein expressed in intestinal goblet cells that maintains and repairs intestinal mucosa by promoting epithelial cell mobility during healing processes. Mutations cause congenital diarrhea with intestinal atresias, malrotations, and dysmotility following autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation, consistent with recessive disease requiring biallelic mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
100 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 | 80 | 0 | 80 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 6 | 8 | 0 | 14 |
Likely Benign | 0 | 0 | 1 | 0 | 1 |
Benign | 0 | 1 | 0 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 0 | 7 | 92 | 0 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TFF3 · 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