SLC2A4

Chr 17

solute carrier family 2 member 4

Also known as: GLUT4

This gene encodes GLUT4, an insulin-regulated facilitative glucose transporter that translocates from intracellular storage compartments to the cell surface upon insulin stimulation to transport glucose into muscle and fat cells. Mutations cause noninsulin-dependent diabetes mellitus with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variation, suggesting tolerance to heterozygous inactivating mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.78
Clinical SummarySLC2A4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 59 VUS of 105 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.38
OE 0.47 (0.290.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.64Z-score
OE missense 0.89 (0.810.99)
259 obs / 289.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.290.78)
00.351.4
Missense OE0.89 (0.810.99)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 11 / 23.4Missense obs/exp: 259 / 289.6Syn Z: -1.29
DN
0.82top 10%
GOF
0.81top 10%
LOF
0.1499th %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

105 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS59
Likely Benign5
Benign1
Conflicting1
26
Pathogenic
3
Likely Pathogenic
59
VUS
5
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
3
0
3
VUS
0
50
9
0
59
Likely Benign
0
4
1
0
5
Benign
0
0
0
1
1
Conflicting
1
Total05439195

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC2A4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →