SLC1A3

solute carrier family 1 member 3, the group of Solute carrier family 1

Basic information

Region (hg38): 5:36596587-36688334

Links

ENSG00000079215 ∙ NCBI:6507 ∙ OMIM:600111 ∙ HGNC:10941 ∙ Uniprot:P43003 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• episodic ataxia type 6 (Limited), mode of inheritance: Unknown
• episodic ataxia type 6 (Supportive), mode of inheritance: AD
• episodic ataxia type 6 (Strong), mode of inheritance: AD
• episodic ataxia type 6 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Episodic ataxia, type 6	AD	Neurologic	Invididuals present with attacks of episodic ataxia, which may be severe in some individuals, and treatment with acetazolamide has been reported as being effective	Neurologic	16116111; 19139306

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC1A3 gene.

• not provided (160 variants)
• Episodic ataxia type 6 (94 variants)
• not specified (25 variants)
• Inborn genetic diseases (19 variants)
• Hereditary episodic ataxia (8 variants)
• Spastic ataxia (1 variants)
• SLC1A3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC1A3 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			9	26	9	44
missense			89	8	1	98
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	3	2	6
non coding			19	12	41	72
Total	0	0	123	46	51

Variants in SLC1A3

This is a list of pathogenic ClinVar variants found in the SLC1A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-36606382-C-T		Hereditary episodic ataxia	Likely benign (Jun 14, 2016)
5-36606551-C-T		Hereditary episodic ataxia	Uncertain significance (Jun 14, 2016)
5-36606626-G-A		Episodic ataxia type 6	Uncertain significance (Jan 12, 2018)
5-36608404-C-A		Episodic ataxia type 6	Uncertain significance (Jan 13, 2018)
5-36608438-T-C		Episodic ataxia type 6 • not specified	Benign/Likely benign (Apr 01, 2024)
5-36608445-G-C		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
5-36608451-A-G		Episodic ataxia type 6	Uncertain significance (Sep 08, 2022)
5-36608459-G-A		not specified	Likely benign (Jul 01, 2023)
5-36608471-G-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
5-36608491-G-A		Episodic ataxia type 6	Benign/Likely benign (Sep 12, 2023)
5-36608492-T-A		Episodic ataxia type 6 • not specified	Benign/Likely benign (Mar 01, 2024)
5-36608493-A-G		Inborn genetic diseases	Uncertain significance (Jun 12, 2023)
5-36608496-C-T			Uncertain significance (Oct 13, 2022)
5-36608497-G-T			Uncertain significance (Jan 28, 2022)
5-36608502-C-T		Episodic ataxia type 6	Conflicting classifications of pathogenicity (Sep 01, 2022)
5-36608507-G-T			Uncertain significance (May 01, 2023)
5-36608508-G-T			Uncertain significance (Sep 19, 2022)
5-36608517-A-C			Uncertain significance (May 19, 2023)
5-36608525-G-A			Likely benign (May 17, 2018)
5-36608532-A-C			Uncertain significance (Jun 01, 2022)
5-36608562-C-G		SLC1A3-related disorder	Uncertain significance (Nov 15, 2022)
5-36608578-T-C			Uncertain significance (Apr 10, 2023)
5-36608579-G-A			Likely benign (Jun 18, 2022)
5-36608591-C-T			Benign/Likely benign (Aug 22, 2023)
5-36629430-T-C			Likely benign (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC1A3	protein_coding	protein_coding	ENST00000265113	9	81980

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0109	125737	0	7	125744	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.79	220	308	0.714	0.0000177	3546
Missense in Polyphen		80	145.75	0.5489		1641
Synonymous	0.212	114	117	0.975	0.00000740	1123
Loss of Function	4.00	2	22.4	0.0892	0.00000144	247

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000549	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.0000549	0.0000544
South Asian	0.00	0.00
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:8123008, PubMed:20477940, PubMed:26690923, PubMed:28032905, PubMed:28424515). 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:20477940). 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:20477940). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity). {ECO:0000250|UniProtKB:P56564, ECO:0000269|PubMed:20477940, ECO:0000269|PubMed:26690923, ECO:0000269|PubMed:28032905, ECO:0000269|PubMed:28424515, ECO:0000269|PubMed:7521911, ECO:0000269|PubMed:8123008}.
• Disease: DISEASE: Episodic ataxia 6 (EA6) [MIM:612656]: A disorder characterized by episodic ataxia, seizures, migraine and alternating hemiplegia. {ECO:0000269|PubMed:16116111}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glutamatergic synapse - Homo sapiens (human);Astrocytic Glutamate-Glutamine Uptake And Metabolism;Synaptic Vesicle Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;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: 0.540

Intolerance Scores

• loftool: 0.425
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.76

Haploinsufficiency Scores

• pHI: 0.298
• hipred: Y
• hipred_score: 0.724
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.417

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc1a3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; vision/eye 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); hearing/vestibular/ear phenotype; neoplasm; 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)

Gene ontology

• Biological process: neurotransmitter uptake;glutamate biosynthetic process;ion transport;chemical synaptic transmission;sensory perception of sound;response to light stimulus;gamma-aminobutyric acid biosynthetic process;response to wounding;glutamate secretion;L-glutamate transmembrane transport;cranial nerve development;auditory behavior;response to antibiotic;cell morphogenesis involved in neuron differentiation;positive regulation of synaptic transmission;neuromuscular process controlling balance;L-glutamate import;D-aspartate import across plasma membrane;potassium ion transmembrane transport;L-glutamate import across plasma membrane;L-aspartate import across plasma membrane;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;membrane;neuron projection;neuronal cell body
• Molecular function: L-glutamate transmembrane transporter activity;high-affinity glutamate transmembrane transporter activity;amino acid transmembrane transporter activity;glutamate:sodium symporter activity;glutamate binding;metal ion binding