SLC1A4 solute carrier family 1 member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC1A4provided by HGNC
Official Full Name: solute carrier family 1 member 4provided by HGNC
Primary source: HGNC:HGNC:10942
See related: Ensembl:ENSG00000115902 MIM:600229; AllianceGenome:HGNC:10942
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SATT; ASCT1; SPATCCM
Summary: The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]
Expression: Broad expression in brain (RPKM 33.8), adrenal (RPKM 12.8) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p14

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (64988479..65023865)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (64998100..65033490)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (65215613..65250999)

Chromosome 2 - NC_000002.12 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

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A rare cause of microcephaly, thin corpus callosum and refractory epilepsy due to a novel SLC1A4 gene mutation.
Title: A rare cause of microcephaly, thin corpus callosum and refractory epilepsy due to a novel SLC1A4 gene mutation.
Results suggest that ASCT1/2 may play an important role in regulating extracellular d-serine and NMDA receptor-mediated physiological effects and that ASCT1/2 inhibitors have the potential for therapeutic benefit.
Title: Phenylglycine analogs are inhibitors of the neutral amino acid transporters ASCT1 and ASCT2 and enhance NMDA receptor-mediated LTP in rat visual cortex slices.
ANKRD50 simultaneously engages multiple parts of the SNX27-retromer-WASH complex machinery in a direct and co-operative interaction network that is needed to efficiently recycle the nutrient transporters
Title: Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50.
SLC1A4 deficiency should not be considered a population-specific disorder, and all patients with unexplained severe neurodevelopmental delay and the features outlined should be investigated regardless of ethnicity, as there are no known metabolic markers of this potentially treatable condition.
Title: Novel European SLC1A4 variant: infantile spasms and population ancestry analysis.
SLC1A4 is the disease causing gene of a novel neurologic disorder manifesting with significant intellectual disability, severe postnatal microcephaly, spasticity and thin corpus callosum.
Title: SLC1A4 mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum.
ASCT1 is essential in brain serine transport.
Title: Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination.
SLC1A4 disruption may impair brain development and function by decreasing the levels of L-serine in neurons. The identification of additional families with mutations in SLC1A4 would be necessary to confirm its involvement in intellectual disability.
Title: A homozygous mutation in SLC1A4 in siblings with severe intellectual disability and microcephaly.
Na+ interactions with the neutral amino acid transporter ASCT1.
Title: Na+ interactions with the neutral amino acid transporter ASCT1.
This study revealed genetic associations of SLC1A4, SQSTM1, and EIF4EBP1 with MSA. These results may lend genetic support to the hypothesis that oxidative stress is associated with the pathogenesis of MSA.
Title: Associations between multiple system atrophy and polymorphisms of SLC1A4, SQSTM1, and EIF4EBP1 genes.
SLC1A4 gene is associated with schizophrenia.
Title: Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9 with schizophrenia.

Submit: New GeneRIF Correction See all GeneRIFs (14)

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

Associated conditions

Description	Tests
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome MedGen: C4225254 OMIM: 616657 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D2S1651E (e-PCR)
- UniSTS:58961

RH70537 (e-PCR)
- UniSTS:71507

D2S421E (e-PCR)
- UniSTS:473196

SLC1A4 (e-PCR)
- UniSTS:513655

RH16636 (e-PCR)
- UniSTS:16003

D2S2566 (e-PCR)
- UniSTS:24988

D2S1652E (e-PCR)
- UniSTS:150700

D2S2858 (e-PCR)
- UniSTS:54719

WI-14351 (e-PCR)
- UniSTS:8428

RH69014 (e-PCR)
- UniSTS:13037

D2S2933 (e-PCR)
- UniSTS:20219

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables L-alanine transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-alanine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-alanine transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables L-aspartate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-aspartate transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
NOT enables L-cystine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-cystine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-glutamine transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed
enables L-hydroxyproline transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-proline transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-serine transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-serine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-serine transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables L-threonine transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-threonine transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables amino acid transmembrane transporter activity	TAS Traceable Author Statement more info
enables chloride channel activity	IDA Inferred from Direct Assay more info	PubMed
enables symporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in L-alanine import across plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in L-alanine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in L-aspartate import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
NOT involved_in L-cystine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in L-cystine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in L-glutamate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in L-serine import across plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in L-serine transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in L-serine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in amino acid transport	TAS Traceable Author Statement more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in cognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glutamine transport	TAS Traceable Author Statement more info	PubMed
involved_in hydroxyproline transport	IDA Inferred from Direct Assay more info	PubMed
involved_in proline transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in proline transport	IDA Inferred from Direct Assay more info	PubMed
involved_in synaptic transmission, glutamatergic	NAS Non-traceable Author Statement more info	PubMed
involved_in threonine transport	IDA Inferred from Direct Assay more info	PubMed
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	HDA more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in intermediate filament	ISS Inferred from Sequence or Structural Similarity more info
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IC Inferred by Curator more info	PubMed
is_active_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: neutral amino acid transporter A

Names: alanine/serine/cysteine/threonine transporter 1; glutamate/neutral amino acid transporter; solute carrier family 1 (glutamate/neutral amino acid transporter), member 4

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.

Genomic

NG_053002.1 RefSeqGene

Range

5955..40421

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193493.2 → NP_001180422.1 neutral amino acid transporter A isoform 2

See identical proteins and their annotated locations for NP_001180422.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform 1.

Source sequence(s)

AK295687, BC026216, BC072423, DA218921

Consensus CDS

CCDS54362.1

UniProtKB/Swiss-Prot

P43007

Related

ENSP00000431942.1, ENST00000531327.5

Conserved Domains (1) summary

cl00573
Location:2 → 179

SDF; Sodium:dicarboxylate symporter family
NM_001348406.2 → NP_001335335.1 neutral amino acid transporter A isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1. Variants 3 and 4 both encode the same isoform (3).

Source sequence(s)

AC007386

Conserved Domains (1) summary

pfam00375
Location:2 → 257

SDF; Sodium:dicarboxylate symporter family
NM_001348407.2 → NP_001335336.1 neutral amino acid transporter A isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1. Variants 3 and 4 both encode the same isoform (3).

Source sequence(s)

AC007386

Conserved Domains (1) summary

pfam00375
Location:2 → 257

SDF; Sodium:dicarboxylate symporter family
NM_003038.5 → NP_003029.2 neutral amino acid transporter A isoform 1

See identical proteins and their annotated locations for NP_003029.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC026216, BC072423, CR990382, L19444

Consensus CDS

CCDS1879.1

UniProtKB/Swiss-Prot

B7Z3C0, D6W5F0, P43007

UniProtKB/TrEMBL

B2R7N6

Related

ENSP00000234256.3, ENST00000234256.4

Conserved Domains (1) summary

pfam00375
Location:72 → 477

SDF; Sodium:dicarboxylate symporter family

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_000002.12 Reference GRCh38.p14 Primary Assembly

Range

64988479..65023865

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

64998100..65033490

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001135581.1: Suppressed sequence

Description

NM_001135581.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.