SLC2A1
solute carrier family 2 member 1, the group of Solute carrier family 2
Basic information
Region (hg38): 1:42925353-42958893
Previous symbols: [ "GLUT1", "GLUT", "HTLVR", "CSE" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- GLUT1 deficiency syndrome 1, autosomal recessive (101 variants)
- not provided (72 variants)
- Encephalopathy due to GLUT1 deficiency (49 variants)
- Dystonia 9 (14 variants)
- Inborn genetic diseases (13 variants)
- Childhood onset GLUT1 deficiency syndrome 2 (10 variants)
- GLUT1 deficiency syndrome (3 variants)
- Intellectual disability (2 variants)
- SLC2A1-related disorder (2 variants)
- Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Hereditary cryohydrocytosis with reduced stomatin;Dystonia 9 (1 variants)
- Dystonia 9;Hereditary cryohydrocytosis with reduced stomatin;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12 (1 variants)
- Dystonia 9;Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Epilepsy, idiopathic generalized, susceptibility to, 12;Hereditary cryohydrocytosis with reduced stomatin (1 variants)
- Myoclonic-astatic epilepsy (1 variants)
- Epilepsy, idiopathic generalized, susceptibility to, 12 (1 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 (1 variants)
- Seizure (1 variants)
- Hereditary cryohydrocytosis with reduced stomatin (1 variants)
- intellectual deficiency;Microcephaly;Epilepsy (1 variants)
- Junctional epidermolysis bullosa gravis of Herlitz (1 variants)
- Hypophosphatasia (1 variants)
- Microcephaly;Abnormality of metabolism/homeostasis (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)
- Encephalopathy due to GLUT1 deficiency;Childhood onset GLUT1 deficiency syndrome 2;Dystonia 9;Epilepsy, idiopathic generalized, susceptibility to, 12;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 | 140 | 10 | 158 | |||
| missense | 36 | 55 | 291 | 389 | ||
| nonsense | 33 | 36 | ||||
| start loss | 5 | |||||
| frameshift | 86 | 94 | ||||
| inframe indel | 20 | |||||
| splice donor/acceptor (+/-2bp) | 19 | 26 | ||||
| splice region | 1 | 3 | 26 | 26 | 2 | 58 |
| non coding | 35 | 87 | 31 | 155 | ||
| Total | 185 | 80 | 343 | 233 | 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:
| 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:
- 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