SLC2A4

Chr 17

solute carrier family 2 member 4

Also known as: GLUT4

NCBI Gene: 6517ENSG00000181856UniProt: P14672

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]

Primary Disease Associations & Inheritance

UniProtType 2 diabetes mellitus
94
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SLC2A4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 58 VUS of 94 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

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.000
Z-score 2.38
OE 0.47 (0.29–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.64Z-score
OE missense 0.89 (0.81–0.99)
259 obs / 289.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.29–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 11 / 23.4Missense obs/exp: 259 / 289.6Syn Z: -1.29

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS58
Likely Benign5
Benign1
Conflicting1
26
Pathogenic
3
Likely Pathogenic
58
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
49
9
0
58
Likely Benign
0
4
1
0
5
Benign
0
0
0
1
1
Conflicting
—1
Total05339194

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Anti-β2glycoprotein I-induced neutrophil extracellular traps cause endothelial activation.
Mancuso S et al.·Rheumatology (Oxford)
2025
Search for common genetic variants to allow reliable Mendelian randomization investigations into ketone metabolism.
Jiesisibieke ZL et al.·Eur J Epidemiol
2025
The mitochondrial hub gene UCHL1 May serve as a potential biomarker for diagnosing diabetic cardiomyopathy: a comprehensive integration of biological pathways.
Gao C et al.·BMC Med Genomics
2025
Glucose Tranporter-4 expression in monocytes: a systematic review.
Mavros Y et al.·Diabetes Res Clin Pract
2009Review
A lysine-restricted diet ameliorates obesity via enrichment of Parabacteroides goldsteinii and 1,4-methylimidazoleacetic acid.
Zhao F et al.·Nat Commun
2025
Correlations between class I glucose transporter expression patterns and clinical outcomes in non-small cell lung cancer.
Nakanishi Y et al.·Thorac Cancer
2023
The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome.
García-Gómez E et al.·Int J Mol Sci
2023
Discovering bioactive pharmaceuticals from natural products for type 2 diabetes mellitus using network pharmacology, molecular docking, and molecular dynamics.
Rahmani B et al.·Sci Rep
2025
Polymorphism in postinsulin receptor signaling pathway is not associated with polycystic ovary syndrome.
Jones MR et al.·Fertil Steril
2008
Increase in tumor suppressor Arf compensates gene dysregulation in in vitro aged adipocytes.
Hasan AU et al.·Biogerontology
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Correction: Integrative multi-omics analyses identify PKD1 and SLC2A4 as genetically supported glycolysis-related candidate genes for rheumatoid arthritis.
A X et al.·Front Immunol
2026🔓 Open Access
Integrative multi-omics analyses identify PKD1 and SLC2A4 as genetically supported glycolysis-related candidate genes for rheumatoid arthritis.
A X et al.·Front Immunol
2025🔓 Open Access
Biphasic Slc2a4 Gene Expression in 3T3-L1 Adipocytes in Response to Treatment with Low and High Concentrations of Daidzein and Genistein.
Gregorio KCR et al.·Curr Issues Mol Biol
2025🔓 Open Access
Enhanced SLC2A4 expression mitigates insulin resistance in gestational diabetes mellitus via the FoxO signaling pathway in vitro.
Jin Y et al.·Exp Ther Med
2025🔓 Open Access
Whole exon screening of SLC2A4 gene and the association of rs5435 with type 2 diabetes in a Bangladeshi case-control study.
Rashid MM et al.·J Genet Eng Biotechnol
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Anterior Cruciate Ligament Reconstruction

Immunometabolic Mechanisms of Blood Flow Restriction (BFR) Training After Anterior Cruciate Ligament Reconstruction

RECRUITING
NCT05012982Phase NAYale UniversityStarted 2023-02-16
AirBanduninflated AirBand

External Resources

Links to major genomics databases and tools