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…

Primary Disease Associations & Inheritance

{Diabetes mellitus, noninsulin-dependent}MIM #125853

Fanconi-Bickel syndromeMIM #227810

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Fanconi-Bickel syndrome; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in SLC2A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

585 rare PASS variants

Rare truncating (LoF)

1 in 1,700

104 rare PASS variants

Rare synonymous (reference)

1 in 270

236 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC2A2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,900
South Asian	~43k	1 in 90	1 in 1,900
Remaining (unassigned)	~30k	1 in 100	1 in 2,300
European (Finnish)	~27k	1 in 350	≈ 1 in 13,000
Admixed American	~22k	1 in 150	1 in 1,400
African / African American	~21k	1 in 110	1 in 780
East Asian	~20k	1 in 200	1 in 2,800
Ashkenazi Jewish	~13k	1 in 570	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 130	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓