SLC2A1

solute carrier family 2 member 1, the group of Solute carrier family 2

Basic information

Region (hg38): 1:42925352-42958893

Previous symbols: [ "GLUT1", "GLUT", "HTLVR", "CSE" ]

Links

ENSG00000117394 ∙ NCBI:6513 ∙ OMIM:138140 ∙ HGNC:11005 ∙ Uniprot:P11166 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• encephalopathy due to GLUT1 deficiency (Definitive), mode of inheritance: AD
• childhood onset GLUT1 deficiency syndrome 2 (Definitive), mode of inheritance: AD
• dystonia 9 (Strong), mode of inheritance: AD
• childhood onset GLUT1 deficiency syndrome 2 (Strong), mode of inheritance: AD
• myoclonic-astatic epilepsy (Supportive), mode of inheritance: Unknown
• dystonia 9 (Supportive), mode of inheritance: AD
• childhood absence epilepsy (Supportive), mode of inheritance: AD
• encephalopathy due to GLUT1 deficiency (Supportive), mode of inheritance: AD
• childhood onset GLUT1 deficiency syndrome 2 (Supportive), mode of inheritance: AD
• hereditary cryohydrocytosis with reduced stomatin (Supportive), mode of inheritance: AD
• encephalopathy due to GLUT1 deficiency (Strong), mode of inheritance: AR
• dystonia 9 (Strong), mode of inheritance: AD
• epilepsy, idiopathic generalized, susceptibility to, 12 (Strong), mode of inheritance: AD
• encephalopathy due to GLUT1 deficiency (Strong), mode of inheritance: AD
• GLUT1 deficiency syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
GLUT1 deficiency syndrome 1; GLUT1 deficiency syndrome 2; Dystonia 9; Epilepsy, idiopathic generalized, susceptibility to, 12; Stomatin-deficient cryohydrocytosis with neurologic defects	AD/AR	Hematologic; Neurologic	Correct diagnosis is important, as ketogenic diet may result in marked clinical improvement of seizures and motor symptoms; Individuals have been described with anemia requiring transfusions; For Dystonia 9, medical management (with acetazolamide and other agents) has been described as beneficial	Hematologic; Neurologic	1575453; 7174793; 8808284; 9462754; 10980529; 11603379; 12555938; 12548383; 15132717; 15180870; 16171377; 15622525; 18451999; 18577546; 19304421; 19630075; 19798636; 19901175; 20574033; 21791420; 21832227; 22282645; 22492876; 23280796; 26336901; 26537434; 28331464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC2A1 gene.

• GLUT1 deficiency syndrome 1, autosomal recessive (640 variants)
• not provided (353 variants)
• Encephalopathy due to GLUT1 deficiency (299 variants)
• Dystonia 9 (223 variants)
• Childhood onset GLUT1 deficiency syndrome 2 (172 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 12 (151 variants)
• Hereditary cryohydrocytosis with reduced stomatin (150 variants)
• not specified (96 variants)
• Inborn genetic diseases (84 variants)
• Intellectual disability (8 variants)
• SLC2A1-related condition (8 variants)
• GLUT1 deficiency syndrome (8 variants)
• Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12;Dystonia 9;Hereditary cryohydrocytosis with reduced stomatin (3 variants)
• Dystonic disorder (2 variants)
• See cases (2 variants)
• Seizure (2 variants)
• Hereditary cryohydrocytosis with reduced stomatin;Dystonia 9;Epilepsy, idiopathic generalized, susceptibility to, 12;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2 (2 variants)
• Dystonia 9;Hereditary cryohydrocytosis with reduced stomatin;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12;Encephalopathy due to GLUT1 deficiency (2 variants)
• Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12;Hereditary cryohydrocytosis with reduced stomatin;Dystonia 9 (2 variants)
• Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2 (2 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 12;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Dystonia 9;Hereditary cryohydrocytosis with reduced stomatin (1 variants)
• 7 conditions (1 variants)
• Hereditary cryohydrocytosis with reduced stomatin;Dystonia 9;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12 (1 variants)
• Microcephaly;Epilepsy;intellectual deficiency (1 variants)
• Developmental disorder (1 variants)
• Myoclonic-astatic epilepsy (1 variants)
• Dystonia 9;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12 (1 variants)
• Paroxysmal dystonia (1 variants)
• Childhood onset GLUT1 deficiency syndrome 2;Hereditary cryohydrocytosis with reduced stomatin;Dystonia 9;Encephalopathy due to GLUT1 deficiency (1 variants)
• Hereditary cryohydrocytosis with reduced stomatin;Epilepsy, idiopathic generalized, susceptibility to, 12;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Dystonia 9 (1 variants)
• Dystonia 9;Hereditary cryohydrocytosis with reduced stomatin;Epilepsy, idiopathic generalized, susceptibility to, 12;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2 (1 variants)
• Hereditary cryohydrocytosis with reduced stomatin;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12;Dystonia 9 (1 variants)
• Microcephaly;Abnormality of metabolism/homeostasis (1 variants)
• Hereditary cryohydrocytosis with reduced stomatin;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Dystonia 9;Epilepsy, idiopathic generalized, susceptibility to, 12 (1 variants)
• Encephalopathy due to GLUT1 deficiency;Epilepsy, idiopathic generalized, susceptibility to, 12;Hereditary cryohydrocytosis with reduced stomatin;Childhood onset GLUT1 deficiency syndrome 2;Dystonia 9 (1 variants)
• Hereditary cryohydrocytosis with reduced stomatin;Epilepsy, idiopathic generalized, susceptibility to, 12;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2 (1 variants)
• SLC2A1-Related Disorders (1 variants)
• Childhood onset GLUT1 deficiency syndrome 2;Encephalopathy due to GLUT1 deficiency;Epilepsy, idiopathic generalized, susceptibility to, 12;Dystonia 9;Hereditary cryohydrocytosis with reduced stomatin (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)
• Strabismus;Seizure;Global developmental delay (1 variants)
• Dystonia 9;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Hereditary cryohydrocytosis with reduced stomatin (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC2A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		7	128	10	146
missense	36	52	273	6	1	368
nonsense	31	4				35
start loss	4	1				5
frameshift	82	7	1			90
inframe indel	5	7	8			20
splice donor/acceptor (+/-2bp)	15	5	2			22
splice region	1	3	26	21	2	53
non coding	1	1	35	74	31	142
Total	175	77	326	208	42

Highest pathogenic variant AF is 0.00000657

Variants in SLC2A1

This is a list of pathogenic ClinVar variants found in the SLC2A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-42925430-A-G		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 13, 2018)
1-42925453-C-T		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Benign (Jan 13, 2018)
1-42925454-T-C		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Benign (Jan 12, 2018)
1-42925477-G-A		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 12, 2018)
1-42925704-T-C		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 13, 2018)
1-42925704-T-G		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 13, 2018)
1-42925720-A-T		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 12, 2018)
1-42925760-T-C		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 13, 2018)
1-42925795-C-T		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 13, 2018)
1-42925828-C-A		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Benign (Jan 12, 2018)
1-42925836-G-A		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 13, 2018)
1-42925892-G-T		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 12, 2018)
1-42925894-C-G		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 13, 2018)
1-42925960-A-T		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 12, 2018)
1-42925962-A-C		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 12, 2018)
1-42926025-T-C		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 13, 2018)
1-42926070-C-T		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Benign (Jan 13, 2018)
1-42926257-T-C		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 13, 2018)
1-42926266-T-C		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 12, 2018)
1-42926291-A-T		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 13, 2018)
1-42926390-C-A		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 13, 2018)
1-42926415-C-T		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Benign (Jan 12, 2018)
1-42926432-C-G		Dystonia 9 • Encephalopathy due to GLUT1 deficiency	Uncertain significance (Jan 12, 2018)
1-42926444-C-T		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 13, 2018)
1-42926454-T-A		Encephalopathy due to GLUT1 deficiency • Dystonia 9	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC2A1	protein_coding	protein_coding	ENST00000426263	10	33479

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00590	125742	0	2	125744	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.93	160	303	0.527	0.0000215	3162
Missense in Polyphen		56	152.96	0.36612		1513
Synonymous	0.116	124	126	0.987	0.00000887	1049
Loss of Function	3.90	1	19.7	0.0508	9.45e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Facilitative glucose transporter. This isoform may be responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses. {ECO:0000269|PubMed:18245775, ECO:0000269|PubMed:19449892}.
• Disease: DISEASE: GLUT1 deficiency syndrome 2 (GLUT1DS2) [MIM:612126]: A clinically variable disorder characterized primarily by onset in childhood of paroxysmal exercise-induced dyskinesia. The dyskinesia involves transient abnormal involuntary movements, such as dystonia and choreoathetosis, induced by exercise or exertion, and affecting the exercised limbs. Some patients may also have epilepsy, most commonly childhood absence epilepsy. Mild mental retardation may also occur. In some patients involuntary exertion- induced dystonic, choreoathetotic, and ballistic movements may be associated with macrocytic hemolytic anemia. {ECO:0000269|PubMed:14605501, ECO:0000269|PubMed:18451999, ECO:0000269|PubMed:19630075, ECO:0000269|PubMed:19798636, ECO:0000269|PubMed:20129935, ECO:0000269|PubMed:20574033, ECO:0000269|PubMed:20621801, ECO:0000269|PubMed:20830593, ECO:0000269|PubMed:21204808}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epilepsy, idiopathic generalized 12 (EIG12) [MIM:614847]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. In some EIG12 patients seizures may remit with age. {ECO:0000269|PubMed:19798636, ECO:0000269|PubMed:22282645, ECO:0000269|PubMed:23280796}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Dystonia 9 (DYT9) [MIM:601042]: An autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most patients show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia. {ECO:0000269|PubMed:21832227}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stomatin-deficient cryohydrocytosis with neurologic defects (SDCHCN) [MIM:608885]: A rare form of stomatocytosis characterized by episodic hemolytic anemia, cold-induced red cells cation leak, erratic hyperkalemia, neonatal hyperbilirubinemia, hepatosplenomegaly, cataracts, seizures, mental retardation, and movement disorder. {ECO:0000269|PubMed:21791420, ECO:0000269|PubMed:22492876}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adipocytokine signaling pathway - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Insulin resistance - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Bile secretion - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Insulin secretion - Homo sapiens (human);GLUT-1 deficiency syndrome;Congenital disorder of glycosylation CDG-IId;Lactose Synthesis;Cori Cycle;HIF1A and PPARG regulation of glycolysis;Nuclear Receptors Meta-Pathway;NRF2 pathway;Photodynamic therapy-induced HIF-1 survival signaling;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Pathways in clear cell renal cell carcinoma;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Type 2 papillary renal cell carcinoma;Insulin Signaling;Glycolysis and Gluconeogenesis;Metabolism of carbohydrates;Vitamin C (ascorbate) metabolism;HIF-2-alpha transcription factor network;Metabolism;Lactose synthesis;SLC-mediated transmembrane transport;Transport of small molecules;Regulation of insulin secretion;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Aminosugars metabolism;Fructose and mannose metabolism;Galactose metabolism;Vitamin C metabolism;Cellular hexose transport;IL3;Integration of energy metabolism;Validated targets of C-MYC transcriptional activation;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.789

Intolerance Scores

• loftool: 0.0901
• rvis_EVS: -1.05
• rvis_percentile_EVS: 7.66

Haploinsufficiency Scores

• pHI: 0.385
• hipred: Y
• hipred_score: 0.825
• ghis: 0.588

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.887

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc2a1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: slc2a1b
• Affected structure: dorsal longitudinal anastomotic vessel
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: response to hypoxia;lactose biosynthetic process;female pregnancy;regulation of glucose transmembrane transport;L-ascorbic acid metabolic process;cerebral cortex development;response to insulin;cellular response to glucose starvation;xenobiotic transport;regulation of insulin secretion;protein-containing complex assembly;dehydroascorbic acid transport;cellular response to mechanical stimulus;cellular hyperosmotic response;response to Thyroglobulin triiodothyronine;glucose transmembrane transport
• Cellular component: Golgi membrane;female pronucleus;cytosol;plasma membrane;integral component of plasma membrane;caveola;intercalated disc;membrane;basolateral plasma membrane;apical plasma membrane;Z disc;midbody;cortical actin cytoskeleton;sarcolemma;melanosome;extracellular exosome;blood microparticle
• Molecular function: glucose transmembrane transporter activity;protein binding;kinase binding;dehydroascorbic acid transmembrane transporter activity;identical protein binding;xenobiotic transmembrane transporter activity;protein self-association;D-glucose transmembrane transporter activity