SLC2A1

Chr 1ADAR

solute carrier family 2 member 1

Also known as: CSE, DYT17, DYT18, DYT9, EIG12, GLUT, GLUT-1, GLUT1

NCBI Gene: 6513 ENSG00000117394 UniProt: P11166 OMIM: 138140

The protein facilitates glucose transport across the blood-brain barrier and provides the brain's primary energy supply through constitutive glucose uptake. Mutations cause GLUT1 deficiency syndrome with infantile-onset seizures and developmental delays or childhood-onset paroxysmal movement disorders, dystonia, and epilepsy through impaired brain glucose transport. Inheritance is autosomal dominant or autosomal recessive depending on the specific mutation and phenotype severity.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a major glucose transporter in the mammalian blood-brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. Mutations in this gene have been found in a family with paroxysmal exertion-induced dyskinesia. [provided by RefSeq, Apr 2013]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.245 OMIM phenotypes

Clinical Summary— SLC2A1

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Gene-Disease Validity (ClinGen)

GLUT1 deficiency syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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Clinical Trials

3 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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.994

Z-score 3.90

OE 0.05 (0.02–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.93Z-score

OE missense 0.53 (0.46–0.60)

160 obs / 303.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.24)

0≤0.351.4

Missense OE?0.53 (0.46–0.60)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 1 / 19.7Missense obs/exp: 160 / 303.4Syn Z: 0.12

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC2A1-related glucose transporter type 1 deficiency syndromeLOFAD

This gene — mechanism propensity

0.6064th %ile

GOF

0.6541th %ile

LOF

0.4135th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · LOEUF 0.24 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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.

Literature Evidence

LOFHaploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS).1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References