SLC25A12 solute carrier family 25 member 12 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC25A12provided by HGNC
Official Full Name: solute carrier family 25 member 12provided by HGNC
Primary source: HGNC:HGNC:10982
See related: Ensembl:ENSG00000115840 MIM:603667; AllianceGenome:HGNC:10982
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: AGC1; DEE39; ARALAR; EIEE39
Summary: This gene encodes a calcium-binding mitochondrial carrier protein. The encoded protein localizes to the mitochondria and is involved in the exchange of aspartate for glutamate across the inner mitochondrial membrane. Polymorphisms in this gene may be associated with autism, and mutations in this gene may also be a cause of global cerebral hypomyelination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]
Expression: Ubiquitous expression in heart (RPKM 23.7), brain (RPKM 13.5) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q31.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (171783405..171894244, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (172260855..172372092, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (172639915..172750754, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

The microRNAs miR-302b and miR-372 regulate mitochondrial metabolism via the SLC25A12 transporter, which controls MAVS-mediated antiviral innate immunity.
Title: The microRNAs miR-302b and miR-372 regulate mitochondrial metabolism via the SLC25A12 transporter, which controls MAVS-mediated antiviral innate immunity.
High SLC25A12 expression significantly associated with poor prognosis of acute myeloid leukemia patients
Title: [Prognostic Value of SLC25A12 Expression in Patients with Acute Myeloid Leukemia Based on Integrated Analysis of Multi-dimensional Clinical Data].
Genetic variants of SLC25A12 may be associated with risks for childhood ASD.
Title: Single Nucleotide Polymorphisms in SLC19A1 and SLC25A9 Are Associated with Childhood Autism Spectrum Disorder in the Chinese Han Population.
The features of AGC1 structure and function in physiology and pathology, regulation by calcium, dependency on mitochondrial membrane potential, role in cancer cells, and tissue specificity are reviewed. AGC1 is involved in the glutamate-mediated excitotoxicity in neurons and AGC gene or protein alterations were discovered in rare human diseases. Review.
Title: AGC1/2, the mitochondrial aspartate-glutamate carriers.
Sensitivity analyses including only studies with family-based design demonstrated significant association between autism spectrum disorders and SNPs rs2292813 and rs2056202. In contrast, sensitivity analyses including case-control design studies only failed to find a significant association. Review.
Title: Mitochondrial Aspartate/Glutamate Carrier SLC25A12 and Autism Spectrum Disorder: a Meta-Analysis.
rs2056202 and rs2292813 in SLC25A12 may contribute significantly to autism spectrum disorders risk.
Title: Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta-analysis.
Structure of the calcium bound and calcium free N- and C-terminal domains is described, elucidating the mechanism of calcium regulation.
Title: Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.
Compares and contrasts all the known human SLC25A* genes and includes functional information.
Title: The mitochondrial transporter family SLC25: identification, properties and physiopathology.
The physiological roles of AGC1, its links to calcium homeostasis, and its involvement in autism pathogenesis, are reviewed.
Title: The mitochondrial aspartate/glutamate carrier AGC1 and calcium homeostasis: physiological links and abnormalities in autism.
This study found no differences in the allele, genotype, or haplotype frequencies of these two SNPs between patients and controls.
Title: Association study of the SLC25A12 gene and autism in Han Chinese in Taiwan.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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
Developmental and epileptic encephalopathy, 39 MedGen: C2751855 OMIM: 612949 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-01-19) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-01-19) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of solute carrier family 25, member 12 (SLC25A12, Aralar) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-145217 (e-PCR)
- UniSTS:174450

SLC25A12_3281 (e-PCR)
- UniSTS:462533

D2S2381 (e-PCR)
- UniSTS:16874

G54269 (e-PCR)
- UniSTS:140789

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-sulfino-L-alanine: proton, glutamate antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables L-aspartate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-glutamate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables acidic amino acid transmembrane transporter activity	EXP Inferred from Experiment more info	PubMed
enables aspartate:glutamate, proton antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in L-aspartate transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in L-glutamate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in L-glutamate transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in aspartate family amino acid metabolic process	TAS Traceable Author Statement more info
involved_in aspartate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in aspartate transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in gluconeogenesis	TAS Traceable Author Statement more info
involved_in malate-aspartate shuttle	IBA Inferred from Biological aspect of Ancestor more info
involved_in malate-aspartate shuttle	IDA Inferred from Direct Assay more info	PubMed
involved_in modified amino acid transport	IEA Inferred from Electronic Annotation more info
involved_in neutral amino acid transport	IEA Inferred from Electronic Annotation more info
involved_in proton transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in response to calcium ion	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial

Names: araceli hiperlarga; aspartate/glutamate carrier 1; calcium binding mitochondrial carrier superfamily member Aralar1; calcium-binding mitochondrial carrier protein Aralar1; mitochondrial aspartate glutamate carrier 1; solute carrier family 25 (aspartate/glutamate carrier), member 12; solute carrier family 25 (mitochondrial carrier, Aralar), member 12

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_011781.2 RefSeqGene

Range

5060..115899

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003705.5 → NP_003696.2 electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial

See identical proteins and their annotated locations for NP_003696.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and is protein-coding.

Source sequence(s)

AC068039, AJ496568

Consensus CDS

CCDS33327.1

UniProtKB/Swiss-Prot

B3KR64, O75746, Q96AM8

UniProtKB/TrEMBL

B3KMV8

Related

ENSP00000388658.2, ENST00000422440.7

Conserved Domains (3) summary

PTZ00169
Location:330 → 603

PTZ00169; ADP/ATP transporter on adenylate translocase; Provisional

pfam00153
Location:514 → 609

Mito_carr; Mitochondrial carrier protein

pfam13499
Location:16 → 80

EF-hand_7; EF-hand domain pair

RNA

NR_047549.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an internal exon in the 5' region, 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)

AC068039, AJ496568, AK091071