SLC2A4

protein-coding

solute carrier family 2 member 4, the group of Solute carrier family 2

Gene summary

This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]

Previous symbols:

GLUT4

MANE transcript

NM_001042.3

Inheritance

—

ClinVar variants

U:55B:6

Top phenotype

Type 2 diabetes mellitus

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr17:7,281,718-7,288,257

External References & Databases

Ensembl (ENSG00000181856)

Transcript & Mutation Effects

hg38 • Region Span ~6.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC2A4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 6

Type 2 diabetes mellitusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			50 clinvar	5 clinvar		55
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	55	5	1	61

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001042.3	RefSeq	NP_001033.1	11	MANE Select
ENST00000317370.13	Ensembl	ENSP00000320935.8	11	MANE Select
ENST00000424875.2	Ensembl	ENSP00000396887.2	10	Standard
ENST00000570783.5	Ensembl	ENSP00000459056.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adipocytokine signaling pathway - Homo sapiens (human)
Type II diabetes mellitus - Homo sapiens (human)
Insulin resistance - Homo sapiens (human)
FoxO signaling pathway - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)

Biological Process

carbohydrate metabolic process
amylopectin biosynthetic process
cellular response to insulin stimulus
glucose homeostasis
glucose import in response to insulin stimulus

Molecular Function

glucose transmembrane transporter activity
protein binding
D-glucose transmembrane transporter activity

Cellular Component

multivesicular body
cytosol
plasma membrane
integral component of plasma membrane
clathrin-coated pit

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317370
Coding exons: 11
Length: 6591
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.638	259	290	0.894	0.0000189	3198
Missense (PolyPhen)		85	104.38	0.81433		1126
Synonymous	-1.29	146	127	1.15	0.00000857	1145
Loss of Function	2.38	11	23.4	0.469	0.00000128	244

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Insulin-regulated facilitative glucose transporter.;
Disease: DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:1521731, ECO:0000269|PubMed:1756912, ECO:0000269|PubMed:1918382}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.304
RVIS EVS: -0.18
RVIS percentile EVS: 40.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.594

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium