SLC6A20
Chr 3solute carrier family 6 member 20
Also known as: IMINO, SIT1, XT3, Xtrp3
The protein functions as a sodium- and chloride-dependent transporter that mediates uptake of imino acids (particularly proline) and glycine, primarily expressed in kidney, small intestine, and brain where it regulates amino acid homeostasis and modulates NMDAR currents. Mutations cause hyperglycinuria and iminoglycinuria, which are autosomal recessive aminoaciduria disorders characterized by excessive urinary excretion of glycine and imino acids. The gene shows high tolerance to loss-of-function variation (pLI nearly zero, LOEUF 1.26), consistent with the recessive inheritance pattern of associated disorders.
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
275 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 | 6 | 0 | 6 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 4 | 109 | 74 | 10 | 197 |
Likely Benign | 0 | 6 | 12 | 11 | 29 |
Benign | 0 | 3 | 29 | 4 | 36 |
Conflicting | — | 2 | |||
| Total | 4 | 118 | 122 | 25 | 271 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC6A20 · 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