TFF2

Chr 21

trefoil factor 2

Also known as: SML1, SP

The TFF2 protein inhibits gastric acid secretion and gastrointestinal motility, and functions as a structural component of gastric mucus by stabilizing glycoproteins in the mucus gel. This gene is highly tolerant to loss-of-function variants, and no established disease associations with TFF2 mutations have been reported in the clinical literature. The gene encodes a trefoil family protein that is part of the gastrointestinal mucosal protective system.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
25
Pubs (1 yr)
89
P/LP submissions
0%
P/LP missense
1.89
LOEUF
GOF
Mechanism· predicted
Clinical SummaryTFF2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
84 unique Pathogenic / Likely Pathogenic· 23 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.000
Z-score -0.74
OE 1.30 (0.771.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.46Z-score
OE missense 0.85 (0.701.05)
67 obs / 78.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.30 (0.771.89)
00.351.4
Missense OE0.85 (0.701.05)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 9 / 6.9Missense obs/exp: 67 / 78.5Syn Z: 0.34
DN
0.5576th %ile
GOF
0.6639th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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

115 submitted variants in ClinVar

Classification Summary

Pathogenic81
Likely Pathogenic3
VUS23
Likely Benign5
Benign2
Conflicting1
81
Pathogenic
3
Likely Pathogenic
23
VUS
5
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
81
0
81
Likely Pathogenic
0
0
3
0
3
VUS
0
15
8
0
23
Likely Benign
0
3
2
0
5
Benign
0
1
0
1
2
Conflicting
1
Total019941115

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TFF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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