SLC5A11

Chr 16

solute carrier family 5 member 11

Also known as: KST1, RKST1, SGLT6, SMIT2

The SLC5A11 protein functions as a sodium-dependent cotransporter that transports myo-inositol and other molecules across cell membranes, particularly in intestinal absorption and renal reabsorption. Mutations in SLC5A11 cause autism spectrum disorder with epilepsy and arthrogryposis, typically presenting in early childhood with developmental delays, seizures, and joint contractures. This gene follows autosomal recessive inheritance and shows tolerance to loss-of-function variants (LOEUF 1.067), affecting primarily neurological and musculoskeletal systems.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.07
Clinical SummarySLC5A11
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 84 VUS of 129 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.26
OE 0.76 (0.551.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.51Z-score
OE missense 0.93 (0.851.01)
367 obs / 395.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.551.07)
00.351.4
Missense OE0.93 (0.851.01)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 24 / 31.6Missense obs/exp: 367 / 395.8Syn Z: -0.10
DN
0.77top 25%
GOF
0.79top 25%
LOF
0.2288th %ile

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.

GOFprediction above median
DNprediction above median

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

129 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS84
Likely Benign4
27
Pathogenic
3
Likely Pathogenic
84
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
59
25
0
84
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total062560118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC5A11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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