SLC1A6 solute carrier family 1 member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC1A6provided by HGNC
Official Full Name: solute carrier family 1 member 6provided by HGNC
Primary source: HGNC:HGNC:10944
See related: Ensembl:ENSG00000105143 MIM:600637; AllianceGenome:HGNC:10944
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EAAT4
Summary: Enables L-aspartate transmembrane transporter activity; L-glutamate transmembrane transporter activity; and glutamate:sodium symporter activity. Involved in L-aspartate import across plasma membrane; L-glutamate import across plasma membrane; and neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in testis (RPKM 7.7), brain (RPKM 2.7) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.12

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (14950033..15010643, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (15074841..15135544, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (15060845..15121455, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Lithium-sensitive GSK3ss is a powerful regulator of excitatory amino acid transporters EAAT3 and EAAT4.
Title: Up-Regulation of Excitatory Amino Acid Transporters EAAT3 and EAAT4 by Lithium Sensitive Glycogen Synthase Kinase GSK3ß.
Decreased SLC1A6 expression in neuregulin 1 risk variant may be an adaptive effect to restore glutamate signalling in schizophrenia patients.
Title: Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment.
A twofold difference in functional EAAT4 levels is sufficient to alter signaling to Bergman glia in reporter mice.
Title: Neuronal glutamate transporters regulate glial excitatory transmission.
strate-dependent gating of anion channels associated with excitatory amino acid transporter 4.
Title: Substrate-dependent gating of anion channels associated with excitatory amino acid transporter 4.
a conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4)
Title: A conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4).
Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
Observational study of gene-disease association. (HuGE Navigator)
Title: L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms.
conclusion, maximal glutamate transport modulation by SGK1 is accomplished by direct EAAT4 stimulation and to a lesser extent by inhibition of intrinsic Nedd4-2.
Title: EAAT4 phosphorylation at the SGK1 consensus site is required for transport modulation by the kinase.
At least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6.
Title: Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia.
Independent, rather than cooperative anion conductance gating significantly alters predictions of the influence that EAAT4-mediated anion currents will have on synaptic transmission at low glutamate concentrations.
Title: The glutamate-activated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

L17705 (e-PCR)
- UniSTS:66091

D8S2279 (e-PCR)
- UniSTS:473907

G38154 (e-PCR)
- UniSTS:53341

WI-16161 (e-PCR)
- UniSTS:79720

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

D1S1423 (e-PCR)
- UniSTS:149619

D19S578 (e-PCR)
- UniSTS:33218

Slc1a6 (e-PCR), detects polymorphism
- UniSTS:547017

G16271 (e-PCR)
- UniSTS:10980

L17791 (e-PCR)
- UniSTS:42740

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables L-aspartate transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-glutamate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-glutamate transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate:sodium symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamate:sodium symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables high-affinity L-glutamate transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables high-affinity L-glutamate transmembrane transporter activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables neutral L-amino acid transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in L-aspartate import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in L-glutamate import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in L-glutamate import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in L-glutamate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in aspartate transmembrane transport	TAS Traceable Author Statement more info	PubMed
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in neurotransmitter transport	TAS Traceable Author Statement more info
involved_in neurotransmitter uptake	IDA Inferred from Direct Assay more info	PubMed
involved_in neurotransmitter uptake	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neurotransmitter uptake	NAS Non-traceable Author Statement more info	PubMed
involved_in neutral amino acid transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of membrane potential	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in intermediate filament cytoskeleton	IDA Inferred from Direct Assay more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
part_of membrane protein complex	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: excitatory amino acid transporter 4

Names: sodium-dependent glutamate/aspartate transporter; solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001272087.2 → NP_001259016.1 excitatory amino acid transporter 4 isoform 1

See identical proteins and their annotated locations for NP_001259016.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 3 encode the same isoform (1).

Source sequence(s)

AC004659, BC028721, BC040604, BI829415, DA059558

Consensus CDS

CCDS62578.1

UniProtKB/Swiss-Prot

P48664

Related

ENSP00000471781.1, ENST00000598504.5

Conserved Domains (1) summary

cl00573
Location:58 → 312

SDF; Sodium:dicarboxylate symporter family
NM_001272088.2 → NP_001259017.1 excitatory amino acid transporter 4 isoform 1

See identical proteins and their annotated locations for NP_001259017.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1 and 3 encode the same isoform (1).

Source sequence(s)

AC004659, BC028721, DA059558, DR004792

Consensus CDS

CCDS62578.1

UniProtKB/Swiss-Prot

P48664

Related

ENSP00000446175.1, ENST00000544886.6

Conserved Domains (1) summary

cl00573
Location:58 → 312

SDF; Sodium:dicarboxylate symporter family
NM_001384669.1 → NP_001371598.1 excitatory amino acid transporter 4 isoform 2

Status: VALIDATED

Source sequence(s)

AC004659

Consensus CDS

CCDS12321.1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063

Related

ENSP00000221742.3, ENST00000221742.7

Conserved Domains (1) summary

pfam00375
Location:58 → 522

SDF; Sodium:dicarboxylate symporter family
NM_001384670.1 → NP_001371599.1 excitatory amino acid transporter 4 isoform 1

Status: VALIDATED

Source sequence(s)

AC004659

Consensus CDS

CCDS62578.1

Conserved Domains (1) summary

cl00573
Location:58 → 312

SDF; Sodium:dicarboxylate symporter family
NM_001384671.1 → NP_001371600.1 excitatory amino acid transporter 4 isoform 3

Status: VALIDATED

Source sequence(s)

AC004659

Conserved Domains (1) summary

cl00573
Location:58 → 117

SDF; Sodium:dicarboxylate symporter family
NM_005071.3 → NP_005062.1 excitatory amino acid transporter 4 isoform 2

See identical proteins and their annotated locations for NP_005062.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 2 which is longer and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC004659

Consensus CDS

CCDS12321.1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063

Related

ENSP00000472133.2, ENST00000594383.2

Conserved Domains (1) summary

pfam00375
Location:58 → 522

SDF; Sodium:dicarboxylate symporter family

RNA

NR_073589.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (4) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK302380, DA200776, DB027852, HY352099, U18244

Related

ENST00000430939.6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

14950033..15010643 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047439234.1 → XP_047295190.1 excitatory amino acid transporter 4 isoform X1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063

Related

ENSP00000471038.1, ENST00000600144.5
XM_047439233.1 → XP_047295189.1 excitatory amino acid transporter 4 isoform X1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063
XM_017027152.3 → XP_016882641.1 excitatory amino acid transporter 4 isoform X1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063

Conserved Domains (1) summary

pfam00375
Location:58 → 522

SDF; Sodium:dicarboxylate symporter family

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

15074841..15135544 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054321792.1 → XP_054177767.1 excitatory amino acid transporter 4 isoform X1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063
XM_054321791.1 → XP_054177766.1 excitatory amino acid transporter 4 isoform X1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063
XM_054321790.1 → XP_054177765.1 excitatory amino acid transporter 4 isoform X1

UniProtKB/Swiss-Prot

P48664, Q8N753

UniProtKB/TrEMBL

M0R063