SLC1A2

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

Basic information

Region (hg38): 11:35251205-35420063

Links

ENSG00000110436

∙ NCBI:6506 ∙ OMIM:600300 ∙ HGNC:10940 ∙ Uniprot:P43004 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
developmental and epileptic encephalopathy, 41 (Moderate), mode of inheritance: AR
developmental and epileptic encephalopathy, 41 (Strong), mode of inheritance: AD
developmental and epileptic encephalopathy, 41 (Limited), mode of inheritance: AR
developmental and epileptic encephalopathy, 41 (Definitive), mode of inheritance: AD
developmental and epileptic encephalopathy, 41 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 41	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23934111; 27476654

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC1A2 gene.

not_provided (433 variants)
Inborn_genetic_diseases (46 variants)
Developmental_and_epileptic_encephalopathy,_41 (45 variants)
not_specified (18 variants)
SLC1A2-related_disorder (18 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC1A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004171.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	104 clinvar	17 clinvar	122
missense	2 clinvar	7 clinvar	174 clinvar	51 clinvar	28 clinvar	262
nonsense			2 clinvar			2
start loss				2		2
frameshift		1 clinvar	7 clinvar			8
splice donor/acceptor (+/-2bp)			4 clinvar	1 clinvar		5
Total	2	8	188	158	45

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC1A2	protein_coding	protein_coding	ENST00000278379	11	168858

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.710	0.290	125739	0	6	125745	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	217	335	0.649	0.0000179	3756
Missense in Polyphen		55	144.97	0.37939		1632
Synonymous	-0.286	135	131	1.03	0.00000771	1181
Loss of Function	3.51	4	21.6	0.185	0.00000113	259

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	0.0000463	0.0000462
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7521911, PubMed:14506254, PubMed:15265858, PubMed:26690923). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:14506254). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:14506254). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (By similarity). {ECO:0000250|UniProtKB:P43006, ECO:0000269|PubMed:15265858, ECO:0000269|PubMed:26690923, ECO:0000269|PubMed:7521911}.;
Disease: DISEASE: Epileptic encephalopathy, early infantile, 41 (EIEE41) [MIM:617105]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE41 inheritance is autosomal dominant. {ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:28777935}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Glutamatergic synapse - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Astrocytic Glutamate-Glutamine Uptake And Metabolism;Purine metabolism;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Neuronal System;Histidine metabolism;Glutamate Neurotransmitter Release Cycle;Neurotransmitter release cycle;Neurotransmitter uptake and metabolism In glial cells;Transmission across Chemical Synapses (Consensus)

Recessive Scores

pRec: 0.385

Intolerance Scores

loftool: 0.145
rvis_EVS: -1.29
rvis_percentile_EVS: 5.03

Haploinsufficiency Scores

pHI: 0.570
hipred: Y
hipred_score: 0.715
ghis: 0.607

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.720

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc1a2
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; normal phenotype; 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: slc1a2b
Affected structure: ON-bipolar cell
Phenotype tag: abnormal
Phenotype quality: functionality

Gene ontology

Biological process: ion transport;chemical synaptic transmission;visual behavior;response to wounding;multicellular organism aging;glutamate secretion;L-glutamate transmembrane transport;telencephalon development;adult behavior;cellular response to extracellular stimulus;multicellular organism growth;response to amino acid;positive regulation of glucose import;protein homotrimerization;D-aspartate import across plasma membrane;L-glutamate import across plasma membrane;neurotransmitter reuptake
Cellular component: plasma membrane;integral component of plasma membrane;cell surface;membrane;axolemma;glutamatergic synapse;integral component of presynaptic membrane
Molecular function: L-glutamate transmembrane transporter activity;high-affinity glutamate transmembrane transporter activity;protein binding;amino acid transmembrane transporter activity;glutamate:sodium symporter activity;metal ion binding