SLC2A8

Chr 9

solute carrier family 2 member 8

Also known as: GLUT8, GLUTX1

The protein is an insulin-regulated glucose transporter that facilitates transport of glucose, fructose, and other hexoses across cell membranes, and also mediates hepatic influx of dietary trehalose which triggers metabolic signaling pathways. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features. The gene shows minimal constraint against loss-of-function variants based on population data.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.10
Clinical SummarySLC2A8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.26
OE 0.68 (0.431.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.94 (0.851.04)
246 obs / 261.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.431.10)
00.351.4
Missense OE0.94 (0.851.04)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 12 / 17.7Missense obs/exp: 246 / 261.9Syn Z: 0.98
DN
0.80top 25%
GOF
0.74top 25%
LOF
0.1994th %ile

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.

DNprediction above median
GOFprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC2A8 · 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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗