SLC2A2

protein-coding

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

Gene summary

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]

Previous symbols:

GLUT2

MANE transcript

NM_000340.2

Inheritance

ClinVar variants

P:64U:142B:69

Top phenotype

Fanconi-Bickel syndrome; Glycogen storage disease XI; Neonatal diabetes mellitus

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr3:170,996,347-171,026,743

External References & Databases

Ensembl (ENSG00000163581)

Transcript & Mutation Effects

hg38 • Region Span ~30.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

permanent neonatal diabetes mellitusSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100164

Submitter: Genomics England PanelApp

neonatal diabetes mellitusSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0016391

Submitter: Genomics England PanelApp

glycogen storage disease due to GLUT2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009216

Submitter: Genomics England PanelApp

transient neonatal diabetes mellitusSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020525

Submitter: Genomics England PanelApp

glycogen storage disease due to GLUT2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009216

Submitter: Labcorp Genetics (formerly Invitae)

glycogen storage disease due to GLUT2 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009216

Submitter: Orphanet

glycogen storage disease due to GLUT2 deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009216

Submitter: Natera

glycogen storage disease due to GLUT2 deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009216

Submitter: G2P

glycogen storage disease due to GLUT2 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009216

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Fanconi-Bickel syndrome; Glycogen storage disease XI; Neonatal diabetes mellitusAR

Manifestation: Biochemical; Endocrine; Gastrointestinal; Renal

Intervention: Biochemical; Endocrine

Rationale: Dietary measures (eg, frequent feeds, cornstarch) can be beneficial; In mildly affected individuals, dietary measures (eg, free glucose and galactose restriction) may be beneficial in terms of growth; Individuals may also manifest with neonatal diabetes mellitus, and awareness may allow preventive measures and prompt treatment related to severe episodes

Refs: 15397919; 6274135; 3153325; 8362811; 7632512; 7564233; 9266402; 9354798; 10987651; 11044475; 11810292; 19480329; 21271664; 22145468; 22350464; 22214819; 22060631; 22831748; 22660720

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC2A2 variants in ClinVar

9 Conditions Cataloged

Fanconi-Bickel syndromeTotal: 254

Type 2 diabetes mellitusTotal: 70

Inborn genetic diseasesTotal: 54

not providedTotal: 43

SLC2A2-related disorderTotal: 32

not specifiedTotal: 25

Monogenic diabetesTotal: 6

Diabetes mellitus type 2, susceptibility toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000340.2. 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			6 clinvar	57 clinvar		63
missense	2 clinvar	9 clinvar	134 clinvar	10 clinvar	2 clinvar	157
nonsense	11 clinvar	3 clinvar	1 clinvar			15
start loss	2 clinvar					2
frameshift	16 clinvar	8 clinvar	1 clinvar			25
splice donor/acceptor (+/-2bp)	7 clinvar	6 clinvar				13
Total	38	26	142	67	2	275

Highest pathogenic variant AF is 0.000095297175

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000340.2	RefSeq	NP_000331.1	11	MANE Select
ENST00000314251.8	Ensembl	ENSP00000323568.3	11	MANE Select
NM_001278658.2	RefSeq	NP_001265587.1	9	Standard
NM_001278659.2	RefSeq	NP_001265588.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
slc2a2	Danio rerio	Structure: whole organism Quality: dead abnormal

Gene / Model

Organism

Observed Phenotype

slc2a2

Danio rerio

Structure: whole organism

Quality: dead

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Central carbon metabolism in cancer - Homo sapiens (human)
Type II diabetes mellitus - Homo sapiens (human)
Insulin resistance - Homo sapiens (human)
Carbohydrate digestion and absorption - Homo sapiens (human)
Maturity onset diabetes of the young - Homo sapiens (human)

Biological Process

carbohydrate metabolic process
hexose transmembrane transport
regulation of insulin secretion
dehydroascorbic acid transport
intestinal hexose absorption

Molecular Function

glucose transmembrane transporter activity
hexose transmembrane transporter activity
dehydroascorbic acid transmembrane transporter activity
D-glucose transmembrane transporter activity

Cellular Component

cytoplasm
plasma membrane
integral component of plasma membrane
brush border
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314251
Coding exons: 11
Length: 30403
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.936	227	270	0.840	0.0000134	3393
Missense (PolyPhen)		87	106.8	0.81461		1398
Synonymous	0.104	96	97.3	0.987	0.00000492	1061
Loss of Function	1.87	16	26.3	0.608	0.00000157	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00043	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00014	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Facilitative glucose transporter. This isoform likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of the beta cell. May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney.;
Disease: DISEASE: Fanconi-Bickel syndrome (FBS) [MIM:227810]: Rare, well- defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose. {ECO:0000269|PubMed:10987651, ECO:0000269|PubMed:11044475}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.731

Intolerance Scores

LoFtool: 0.471
RVIS EVS: -0.22
RVIS percentile EVS: 37.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.736

Gene Damage Prediction

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