SLC2A4

Chr 17

solute carrier family 2 member 4

Also known as: GLUT4

NCBI Gene: 6517 ENSG00000181856 UniProt: P14672 OMIM: 138190

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.78

Clinical Summary— SLC2A4

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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

50 VUS of 67 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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?

0.78LOEUF

pLI 0.000

Z-score 2.38

OE 0.47 (0.29–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.64Z-score

OE missense 0.89 (0.81–0.99)

259 obs / 289.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.29–0.78)

0≤0.351.4

Missense OE?0.89 (0.81–0.99)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 11 / 23.4Missense obs/exp: 259 / 289.6Syn Z: -1.29

This gene — mechanism propensity

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

67 submitted variants in ClinVar

ClinVar

Classification Summary

VUS50

Likely Benign5

Benign1

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	50	0	0	50
Likely Benign	0	4	1	0	5
Benign	0	0	0	1	1
Conflicting	—				1
Total	0	54	1	1	57

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap SLC2A4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →