SLC5A12
Chr 11solute carrier family 5 member 12
Also known as: SMCT2
The SLC5A12 protein functions as a low-affinity sodium-coupled transporter that mediates reabsorption of monocarboxylates including lactate, pyruvate, and other organic acids in the proximal tubule of the kidney and small intestine. Mutations in SLC5A12 cause autosomal recessive renal lactate wasting, which can lead to metabolic complications due to impaired lactate reabsorption. This gene is not highly constrained against loss-of-function variants, 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 (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
118 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 | 20 | 0 | 20 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 75 | 8 | 0 | 83 |
Likely Benign | 0 | 2 | 0 | 2 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 77 | 29 | 2 | 108 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC5A12 · 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