SLC5A11

Chr 16

solute carrier family 5 member 11

Also known as: KST1, RKST1, SGLT6, SMIT2

NCBI Gene: 115584 ENSG00000158865 UniProt: Q8WWX8 OMIM: 610238

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.

OMIM ResearchSummary from RefSeq, UniProt

Cotransporters, such as SLC5A11, represent a major class of proteins that make use of ion gradients to drive active transport for the cellular accumulation of nutrients, neurotransmitters, osmolytes, and ions Roll et al. (2002) [PubMed 12039040].[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.07

Clinical Summary— SLC5A11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

81 VUS of 95 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.26

OE 0.76 (0.55–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.51Z-score

OE missense 0.93 (0.85–1.01)

367 obs / 395.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.55–1.07)

0≤0.351.4

Missense OE?0.93 (0.85–1.01)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 24 / 31.6Missense obs/exp: 367 / 395.8Syn Z: -0.10

This gene — mechanism propensity

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

95 submitted variants in ClinVar

ClinVar

Classification Summary

VUS81

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	59	22	81
Likely Benign	3	1	4
Benign	0	0	0
Total	62	23	85

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap SLC5A11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →