SLC19A2
Chr 1ARsolute carrier family 19 member 2
Also known as: TC1, THMD1, THT1, THTR1, TRMA
This gene encodes a high-affinity thiamine transporter that mediates cellular uptake of thiamine (vitamin B1) and also transports pyridoxine in a proton-dependent manner. Mutations cause thiamine-responsive megaloblastic anemia syndrome, an autosomal recessive disorder characterized by the triad of diabetes mellitus, megaloblastic anemia, and sensorineural deafness. The gene shows low constraint against loss-of-function variants (pLI 0.0004), consistent with its recessive inheritance pattern.
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
SLC19A2 · 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