SLC1A1

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

Basic information

Region (hg38): 9:4490468-4587469

Links

ENSG00000106688 ∙ NCBI:6505 ∙ OMIM:133550 ∙ HGNC:10939 ∙ Uniprot:P43005 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hot water reflex epilepsy (Supportive), mode of inheritance: AD
• dicarboxylic aminoaciduria (Strong), mode of inheritance: AR
• dicarboxylic aminoaciduria (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dicarboxylic aminoaciduria	AR	Renal	Individuals are at high risk of nephrolithiasis, and awareness may allow preventive measures and early management	Neurologic; Renal	21123949; 23341099

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC1A1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC1A1 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	5	8	22
missense		1	46	2	2	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			4	2	2	8
non coding			53	9	32	94
Total	0	2	109	16	42

Variants in SLC1A1

This is a list of pathogenic ClinVar variants found in the SLC1A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-4490469-C-T		Dicarboxylic aminoaciduria	Likely benign (Jan 13, 2018)
9-4490495-G-C		Dicarboxylic aminoaciduria	Uncertain significance (Jan 12, 2018)
9-4490513-C-G		Dicarboxylic aminoaciduria	Likely benign (Jan 12, 2018)
9-4490587-G-A		Dicarboxylic aminoaciduria	Likely benign (Jan 13, 2018)
9-4490594-G-C		Dicarboxylic aminoaciduria	Uncertain significance (Jan 12, 2018)
9-4490689-C-T		not specified	Uncertain significance (Feb 28, 2024)
9-4490692-G-A		not specified	Uncertain significance (Jul 20, 2021)
9-4490702-G-A		not specified	Uncertain significance (Jan 19, 2024)
9-4490715-G-C		not specified	Uncertain significance (Aug 17, 2021)
9-4490724-G-A			Likely benign (Mar 28, 2018)
9-4490752-G-C		Dicarboxylic aminoaciduria	Uncertain significance (Jan 13, 2018)
9-4490756-C-G		not specified	Uncertain significance (Dec 08, 2023)
9-4490760-G-C		Dicarboxylic aminoaciduria	Benign (Jan 13, 2018)
9-4490760-G-T			Likely benign (Jan 04, 2018)
9-4490770-G-C			Uncertain significance (Sep 16, 2018)
9-4490780-G-A		Dicarboxylic aminoaciduria	Uncertain significance (Jan 13, 2018)
9-4490880-T-C			Benign (Nov 12, 2018)
9-4544590-C-T			Uncertain significance (Sep 16, 2018)
9-4544595-A-G		Dicarboxylic aminoaciduria	Uncertain significance (Jan 13, 2018)
9-4544598-C-T		Dicarboxylic aminoaciduria	Conflicting classifications of pathogenicity (Aug 22, 2018)
9-4544601-C-G		not specified	Uncertain significance (Sep 28, 2022)
9-4544615-T-C		not specified	Uncertain significance (May 24, 2024)
9-4544624-T-A		Dicarboxylic aminoaciduria • SLC1A1-related disorder	Benign (Dec 31, 2019)
9-4544640-T-C		Dicarboxylic aminoaciduria	Benign (Aug 01, 2024)
9-4544648-T-A		Dicarboxylic aminoaciduria	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC1A1	protein_coding	protein_coding	ENST00000262352	12	97026

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000869	0.984	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.33	355	291	1.22	0.0000168	3424
Missense in Polyphen		129	119.01	1.084		1426
Synonymous	-2.99	149	109	1.36	0.00000688	1065
Loss of Function	2.18	12	23.3	0.514	0.00000135	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000260	0.000260
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000231	0.000231
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
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:7914198, PubMed:7521911, PubMed:8857541, PubMed:26690923, PubMed:21123949). Can also transport L-cysteine (PubMed:21123949). 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:7521911, PubMed:8857541, PubMed:26690923). 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:8857541, PubMed:26690923). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:21123949). 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). Negatively regulated by ARL6IP5 (By similarity). {ECO:0000250|UniProtKB:P51906, ECO:0000250|UniProtKB:P51907, ECO:0000269|PubMed:21123949, ECO:0000269|PubMed:26690923, ECO:0000269|PubMed:7521911, ECO:0000269|PubMed:7914198, ECO:0000269|PubMed:8857541}.
• Disease: DISEASE: Dicarboxylic aminoaciduria (DCBXA) [MIM:222730]: An autosomal recessive disorder characterized by abnormal excretion of urinary glutamate and aspartate, resulting from the incomplete reabsorption of anionic amino acids from the glomerular filtrate in the kidney. It can be associated with mental retardation. {ECO:0000269|PubMed:21123949}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Schizophrenia 18 (SCZD18) [MIM:615232]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:21982423, ECO:0000269|PubMed:23341099}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A deletion at the chromosome 9p24.2 locus, including SLC1A1, has been identified in patients with psychotic disorders (PubMed:21982423). This 84 kb deletion is immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence, extends through exon 1 of the SLC1A1 mRNA, co-segregates with disease in an extended 5-generation pedigree and increases disease risk more than 18-fold for family members (PubMed:23341099). {ECO:0000269|PubMed:21982423, ECO:0000269|PubMed:23341099}.
• Pathway: Glutamatergic synapse - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Cystinuria;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Kidney Function;Glucose Transporter Defect (SGLT2);Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;Chlorothiazide Action Pathway;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;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.367

Intolerance Scores

• loftool: 0.555
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.67

Haploinsufficiency Scores

• pHI: 0.336
• hipred: Y
• hipred_score: 0.500
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.575

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc1a1
• Phenotype: renal/urinary system 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); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: ion transport;chemical synaptic transmission;positive regulation of heart rate;glutamate secretion;L-glutamate transmembrane transport;cysteine transport;protein homooligomerization;L-glutamate import;D-aspartate import across plasma membrane;L-glutamate import across plasma membrane;L-aspartate import across plasma membrane;chloride transmembrane transport;cysteine transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;apical plasma membrane;extracellular exosome
• Molecular function: L-glutamate transmembrane transporter activity;high-affinity glutamate transmembrane transporter activity;protein binding;chloride transmembrane transporter activity;amino acid transmembrane transporter activity;glutamate:sodium symporter activity;glutamate binding;cysteine transmembrane transporter activity;metal ion binding