SLC6A18
Chr 5solute carrier family 6 member 18
Also known as: Xtrp2
SLC6A18 encodes a sodium-coupled transporter protein that belongs to the SLC6 family, though it lacks detectable neutral amino acid transporter activity. Mutations cause iminoglycinuria (autosomal recessive), a generally benign condition characterized by excessive urinary excretion of glycine, proline, and hydroxyproline. The gene shows low constraint against loss-of-function variants, consistent with the mild clinical phenotype associated with its dysfunction.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
122 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 | 23 | 0 | 23 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 1 | 76 | 7 | 0 | 84 |
Likely Benign | 0 | 10 | 0 | 0 | 10 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 86 | 30 | 0 | 117 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC6A18 · 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