SLC2A8

Chr 9

solute carrier family 2 member 8

Also known as: GLUT8, GLUTX1

NCBI Gene: 29988 ENSG00000136856 UniProt: Q9NY64 OMIM: 605245

The protein is an insulin-regulated glucose transporter that facilitates transport of glucose, fructose, and other hexoses across cell membranes, and also mediates hepatic influx of dietary trehalose which triggers metabolic signaling pathways. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features. The gene shows minimal constraint against loss-of-function variants based on population data.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the solute carrier 2A family, which includes intracellular glucose transporters. Based on sequence comparison, the glucose transporters are grouped into three classes and this gene is a member of class II. The encoded protein, like other members of the family, contains several conserved residues and motifs and 12 transmembrane domains with both amino and carboxyl ends being on the cytosolic side of the membrane. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.10

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.26

OE 0.68 (0.43–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.94 (0.85–1.04)

246 obs / 261.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.43–1.10)

0≤0.351.4

Missense OE?0.94 (0.85–1.04)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 12 / 17.7Missense obs/exp: 246 / 261.9Syn Z: 0.98

Background carrier burden — how many people carry a rare variant somewhere in SLC2A8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 52

753 rare PASS variants

Rare truncating (LoF)

1 in 250

147 rare PASS variants

Rare synonymous (reference)

1 in 100

307 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SLC2A8; this gene does not show strong loss-of-function constraint by this measure. 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 83	1 in 400
South Asian	~43k	1 in 54	1 in 280
Remaining (unassigned)	~30k	1 in 52	1 in 380
European (Finnish)	~27k	1 in 240	1 in 1,500
Admixed American	~22k	1 in 74	1 in 540
African / African American	~21k	1 in 59	1 in 390
East Asian	~20k	1 in 58	1 in 620
Ashkenazi Jewish	~13k	1 in 580	≈ 1 in 3,000
Middle Eastern	~2,884	1 in 41	≈ 1 in 1,200

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): 8 of 10 coding exons well covered in gnomAD exomes; exons 1, 2 marginal. Genomes: all 10.? see exons ↓