SLC2A3

Chr 12

solute carrier family 2 member 3

Also known as: GLUT3

NCBI Gene: 6515ENSG00000059804UniProt: P11169

SLC2A3 encodes GLUT3, a facilitative glucose transporter that mediates uptake of glucose and other monosaccharides across cell membranes, including transport across the blood-brain barrier. Mutations cause SLC2A3-related disorders with autosomal dominant inheritance, presenting with developmental delays, seizures, and movement disorders due to impaired brain glucose transport. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.65), reflecting its essential role in cellular glucose metabolism.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
57
Pubs (1 yr)
44
P/LP submissions
0%
P/LP missense
0.65
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SLC2A3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 64 VUS of 140 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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
0.65LOEUF
pLI 0.010
Z-score 2.72
OE 0.35 (0.20–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.03Z-score
OE missense 0.83 (0.74–0.92)
237 obs / 286.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.20–0.65)
0≤0.351.4
Missense OE0.83 (0.74–0.92)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 7 / 20.2Missense obs/exp: 237 / 286.2Syn Z: -0.92
DN
0.86top 5%
GOF
0.82top 10%
LOF
0.1299th %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

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic2
VUS64
Likely Benign13
Benign7
41
Pathogenic
2
Likely Pathogenic
64
VUS
13
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
41
0
41
Likely Pathogenic
0
0
2
0
2
VUS
0
57
7
0
64
Likely Benign
0
4
6
3
13
Benign
0
0
6
1
7
Total061624127

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC2A3 · 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 →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SLC2A3-Mediated Lactate Metabolism Promotes Lung Cancer Bone Metastasis by Modulating P53 Lactylation and Immune Evasion.
Ding Y et al.·Adv Sci (Weinh)
2026
Disulfidptosis in osteoarthritis: Role of SLC2A3 downregulation and potential therapeutic implications.
Feng R et al.·Exp Gerontol
2026
Pan-cancer analysis and experimental verification of its roles and clinical significance of SLC2A3 in kidney renal clear cell carcinoma.
Lyu Z et al.·Front Immunol
2025Open Access
Integrated Multiomics Analysis and Machine Learning Approaches in Bladder Cancer: Unveiling the Impact of Immunogenic Cell Death and Its Key Gene SLC2A3 on Prognosis and Personalized Treatment Strategies.
Sun M et al.·ACS Omega
2025Open Access
Transcriptional Expression of SLC2A3 and SDHA Predicts the Risk of Local Tumor Recurrence in Patients with Head and Neck Squamous Cell Carcinomas Treated Primarily with Radiotherapy or Chemoradiotherapy.
Camacho M et al.·Int J Mol Sci
2025Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients