TM4SF5
Chr 17transmembrane 4 L six family member 5
TM4SF5 encodes a transmembrane glycoprotein that acts as a lysosomal membrane arginine sensor and forms complexes with mTOR and SLC38A9 to regulate mTORC1 activation and cell cycle progression. The gene shows low constraint against loss-of-function variants (pLI 0.008, LOEUF 0.97), and no definitive Mendelian diseases have been established from TM4SF5 mutations in current medical literature. Overexpression has been associated with tumor cell growth, but pathogenic germline variants causing pediatric neurological conditions have not been well-characterized.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TM4SF5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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