SLC2A2

Chr 3ADAR

solute carrier family 2 member 2

Also known as: GLUT2

NCBI Gene: 6514 ENSG00000163581 UniProt: P11168 OMIM: 138160

The protein is a facilitative glucose transporter that mediates bidirectional transport of glucose, fructose, and galactose across cell membranes in liver, pancreatic beta cells, intestine, and kidney, functioning as part of the glucose-sensing mechanism in beta cells. Mutations cause Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus with both autosomal recessive and autosomal dominant inheritance patterns. The gene is not highly constrained against loss-of-function variants, and the clinical phenotypes primarily affect glucose homeostasis and renal tubular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.922 OMIM phenotypes

Clinical Summary— SLC2A2

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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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Clinical Trials

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

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC2A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.000

Z-score 1.87

OE 0.61 (0.41–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.94Z-score

OE missense 0.84 (0.75–0.94)

227 obs / 270.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.41–0.92)

0≤0.351.4

Missense OE?0.84 (0.75–0.94)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 16 / 26.3Missense obs/exp: 227 / 270.3Syn Z: 0.10

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC2A2-related Fanconi-Bickel syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.82top 10%

GOF

0.74top 25%

LOF

0.1697th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNEctopic expression in PANC-1 cells of dominant negative or constitutively active mutants of RAC1 activation blocked or enhanced, respectively, the cytokine-induced activation of a ductal-to-endocrine transdifferentiation transcriptional program (deTDtP) as revealed by induction of the NEUROG3, INS, 1

GOFNaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References