TM7SF3
Chr 12transmembrane 7 superfamily member 3
The TM7SF3 protein is a plasma membrane protein that promotes pancreatic beta cell survival by inhibiting cytokine-induced cell death and attenuating endoplasmic reticulum stress, while also promoting insulin secretion. Mutations cause autosomal recessive congenital hyperinsulinism, typically presenting in the neonatal period with severe hypoglycemia. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
140 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 | 33 | 0 | 33 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 72 | 1 | 0 | 73 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 75 | 35 | 0 | 110 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TM7SF3 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools