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 ... See more...

Aliases for SLC25A12 Gene

Aliases for SLC25A12 Gene

  • Solute Carrier Family 25 Member 12 2 3 4 5
  • Solute Carrier Family 25 (Mitochondrial Carrier, Aralar), Member 12 2 3
  • Solute Carrier Family 25 (Aspartate/Glutamate Carrier), Member 12 2 3
  • Calcium-Binding Mitochondrial Carrier Protein Aralar1 3 4
  • Mitochondrial Aspartate Glutamate Carrier 1 3 4
  • Calcium Binding Mitochondrial Carrier Superfamily Member Aralar1 3
  • Araceli Hiperlarga 3
  • ARALAR1 4
  • ARALAR 3
  • EIEE39 3
  • AGC1 3

External Ids for SLC25A12 Gene

Previous GeneCards Identifiers for SLC25A12 Gene

  • GC02M170692
  • GC02M171182
  • GC02M172604
  • GC02M172843
  • GC02M172466
  • GC02M172349
  • GC02M164525

Summaries for SLC25A12 Gene

Entrez Gene Summary for SLC25A12 Gene

  • 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]

GeneCards Summary for SLC25A12 Gene

SLC25A12 (Solute Carrier Family 25 Member 12) is a Protein Coding gene. Diseases associated with SLC25A12 include Epileptic Encephalopathy, Early Infantile, 39 and Asperger Syndrome. Among its related pathways are Mitochondrial protein import and Glycosaminoglycan metabolism. Gene Ontology (GO) annotations related to this gene include calcium ion binding and L-aspartate transmembrane transporter activity. An important paralog of this gene is SLC25A13.

UniProtKB/Swiss-Prot Summary for SLC25A12 Gene

  • Mitochondrial and calcium-binding carrier that catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane (PubMed:11566871, PubMed:25410934). May have a function in the urea cycle (PubMed:11566871).

Gene Wiki entry for SLC25A12 Gene

Additional gene information for SLC25A12 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SLC25A12 Gene

Genomics for SLC25A12 Gene

GeneHancer (GH) Regulatory Elements for SLC25A12 Gene

Promoters and enhancers for SLC25A12 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SLC25A12 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SLC25A12 gene promoter:
  • AML1a
  • FOXD3
  • POU2F1
  • POU2F1a
  • POU2F1b
  • POU2F1c
  • Sox5
  • TBP

Genomic Locations for SLC25A12 Gene

Genomic Locations for SLC25A12 Gene
chr2:171,783,405-171,999,859
(GRCh38/hg38)
Size:
216,455 bases
Orientation:
Minus strand
chr2:172,639,915-172,864,766
(GRCh37/hg19)
Size:
224,852 bases
Orientation:
Minus strand

Genomic View for SLC25A12 Gene

Genes around SLC25A12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC25A12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC25A12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC25A12 Gene

Proteins for SLC25A12 Gene

  • Protein details for SLC25A12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75746-CMC1_HUMAN
    Recommended name:
    Calcium-binding mitochondrial carrier protein Aralar1
    Protein Accession:
    O75746
    Secondary Accessions:
    • B3KR64
    • Q96AM8

    Protein attributes for SLC25A12 Gene

    Size:
    678 amino acids
    Molecular mass:
    74762 Da
    Quaternary structure:
    • Homodimer (via N-terminus).
    Miscellaneous:
    • Binds to one calcium ion with high affinity.

    Three dimensional structures from OCA and Proteopedia for SLC25A12 Gene

    Alternative splice isoforms for SLC25A12 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC25A12 Gene

Post-translational modifications for SLC25A12 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SLC25A12 Gene

No data available for DME Specific Peptides for SLC25A12 Gene

Domains & Families for SLC25A12 Gene

Gene Families for SLC25A12 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted intracellular proteins
  • Transporters

Suggested Antigen Peptide Sequences for SLC25A12 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ33752 fis, clone BRCAN2000364, highly similar to Calcium-binding mitochondrial carrier protein Aralar1 (B3KR64_HUMAN)
  • cDNA FLJ57722, highly similar to Calcium-binding mitochondrial carrier protein Aralar1 (B4DGK6_HUMAN)
  • Solute carrier family 25 member 12 (CMC1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O75746

UniProtKB/Swiss-Prot:

CMC1_HUMAN :
  • Upon calcium binding, the EF-hand-containing regulatory N-terminal domain binds to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain (PubMed:25410934). In the absence of calcium, the linker loop domain may close the vestibule, which may prevent substrates from entering the carrier domain (PubMed:25410934).
  • Belongs to the mitochondrial carrier (TC 2.A.29) family.
Domain:
  • Upon calcium binding, the EF-hand-containing regulatory N-terminal domain binds to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain (PubMed:25410934). In the absence of calcium, the linker loop domain may close the vestibule, which may prevent substrates from entering the carrier domain (PubMed:25410934).
Family:
  • Belongs to the mitochondrial carrier (TC 2.A.29) family.
genes like me logo Genes that share domains with SLC25A12: view

Function for SLC25A12 Gene

Molecular function for SLC25A12 Gene

UniProtKB/Swiss-Prot Function:
Mitochondrial and calcium-binding carrier that catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane (PubMed:11566871, PubMed:25410934). May have a function in the urea cycle (PubMed:11566871).

Phenotypes From GWAS Catalog for SLC25A12 Gene

Gene Ontology (GO) - Molecular Function for SLC25A12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005313 L-glutamate transmembrane transporter activity IDA 11566871
GO:0005509 calcium ion binding IDA 9722566
GO:0015183 L-aspartate transmembrane transporter activity IBA,IDA 11566871
GO:0022857 transmembrane transporter activity IEA --
GO:0042802 identical protein binding IDA 25410934
genes like me logo Genes that share ontologies with SLC25A12: view
genes like me logo Genes that share phenotypes with SLC25A12: view

Human Phenotype Ontology for SLC25A12 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC25A12

CRISPR Products

miRNA for SLC25A12 Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC25A12

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for SLC25A12 Gene

Localization for SLC25A12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC25A12 Gene

Mitochondrion inner membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SLC25A12 gene
Compartment Confidence
mitochondrion 5
cytosol 4
nucleus 2
plasma membrane 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (1)
  • Nuclear speckles (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SLC25A12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IEA 9722566
GO:0005743 mitochondrial inner membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA,NAS 9722566
genes like me logo Genes that share ontologies with SLC25A12: view

Pathways & Interactions for SLC25A12 Gene

genes like me logo Genes that share pathways with SLC25A12: view

Pathways by source for SLC25A12 Gene

2 Cell Signaling Technology pathways for SLC25A12 Gene

Gene Ontology (GO) - Biological Process for SLC25A12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006094 gluconeogenesis TAS --
GO:0006537 glutamate biosynthetic process IEA --
GO:0010907 positive regulation of glucose metabolic process IEA --
GO:0015810 aspartate transmembrane transport IBA,IDA 11566871
GO:0015813 L-glutamate transmembrane transport IBA,IDA 11566871
genes like me logo Genes that share ontologies with SLC25A12: view

No data available for SIGNOR curated interactions for SLC25A12 Gene

Drugs & Compounds for SLC25A12 Gene

(2) Drugs for SLC25A12 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Aspartic acid Approved Nutra Target 171
Calcium Approved Nutra 7773

(2) Additional Compounds for SLC25A12 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SLC25A12: view

Transcripts for SLC25A12 Gene

mRNA/cDNA for SLC25A12 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC25A12

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC25A12 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b
SP1: - - -
SP2: - - - -
SP3:
SP4:

Relevant External Links for SLC25A12 Gene

GeneLoc Exon Structure for
SLC25A12
ECgene alternative splicing isoforms for
SLC25A12

Expression for SLC25A12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SLC25A12 Gene

mRNA differential expression in normal tissues according to GTEx for SLC25A12 Gene

This gene is overexpressed in Muscle - Skeletal (x4.7).

Protein differential expression in normal tissues from HIPED for SLC25A12 Gene

This gene is overexpressed in Nasal epithelium (24.3), Heart (12.0), and Frontal cortex (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SLC25A12 Gene



Protein tissue co-expression partners for SLC25A12 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of SLC25A12 Gene:

SLC25A12

SOURCE GeneReport for Unigene cluster for SLC25A12 Gene:

Hs.470608

mRNA Expression by UniProt/SwissProt for SLC25A12 Gene:

O75746-CMC1_HUMAN
Tissue specificity: Expressed predominantly in the heart and skeletal muscle, weakly in brain and kidney.

Evidence on tissue expression from TISSUES for SLC25A12 Gene

  • Nervous system(4.9)
  • Heart(4.4)
  • Muscle(2.2)
  • Pancreas(2.2)
  • Eye(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC25A12 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • eye
  • head
General:
  • spinal cord
genes like me logo Genes that share expression patterns with SLC25A12: view

Orthologs for SLC25A12 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SLC25A12 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SLC25A12 33 32
  • 99.71 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SLC25A12 33
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SLC25A12 33 32
  • 93.87 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SLC25A12 33 32
  • 93.75 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SLC25A12 33
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Slc25a12 17 33 32
  • 88.07 (n)
chicken
(Gallus gallus)
Aves SLC25A12 33 32
  • 80.33 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SLC25A12 33
  • 90 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii slc25a12 33 32
  • 70.69 (n)
ManyToMany
Dr.3511 32
fruit fly
(Drosophila melanogaster)
Insecta aralar1 34 32
  • 59.11 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000958 32
  • 57.78 (n)
worm
(Caenorhabditis elegans)
Secernentea K02F3.2 33 34 32
  • 56.49 (n)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes AGC1 33
  • 27 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5735 33
  • 63 (a)
ManyToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU01241 32
  • 51 (n)
Species where no ortholog for SLC25A12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for SLC25A12 Gene

ENSEMBL:
Gene Tree for SLC25A12 (if available)
TreeFam:
Gene Tree for SLC25A12 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SLC25A12: view image

Paralogs for SLC25A12 Gene

(9) SIMAP similar genes for SLC25A12 Gene using alignment to 5 proteins:

  • CMC1_HUMAN
  • B3KR64_HUMAN
  • B4DGK6_HUMAN
  • F8W9J0_HUMAN
  • H0YFB2_HUMAN
genes like me logo Genes that share paralogs with SLC25A12: view

Variants for SLC25A12 Gene

Sequence variations from dbSNP and Humsavar for SLC25A12 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs10497374 likely-benign, Hypomyelination, global cerebral 171,784,113(-) A/G 3_prime_UTR_variant, downstream_transcript_variant, genic_downstream_transcript_variant, non_coding_transcript_variant
rs113403751 uncertain-significance, Hypomyelination, global cerebral 171,785,109(-) G/A 3_prime_UTR_variant, non_coding_transcript_variant
rs113965617 uncertain-significance, Hypomyelination, global cerebral 171,784,580(-) C/G/T 3_prime_UTR_variant, non_coding_transcript_variant
rs11757 likely-benign, Hypomyelination, global cerebral 171,784,535(-) C/G 3_prime_UTR_variant, non_coding_transcript_variant
rs121434396 pathogenic, Hypomyelination, global cerebral, Epileptic encephalopathy, early infantile, 39 (EIEE39) [MIM:612949] 171,787,637(-) T/C coding_sequence_variant, missense_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for SLC25A12 Gene

Variant ID Type Subtype PubMed ID
dgv2093n106 CNV deletion 24896259
esv2674991 CNV deletion 23128226
esv2721130 CNV deletion 23290073
nsv583611 CNV gain 21841781
nsv834457 CNV loss 17160897

Variation tolerance for SLC25A12 Gene

Residual Variation Intolerance Score: 7.25% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.16; 51.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLC25A12 Gene

Human Gene Mutation Database (HGMD)
SLC25A12
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC25A12

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC25A12 Gene

Disorders for SLC25A12 Gene

MalaCards: The human disease database

(5) MalaCards diseases for SLC25A12 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
epileptic encephalopathy, early infantile, 39
  • eiee39
asperger syndrome
  • asperger disorder
autism
  • autistic disorder
autism spectrum disorder
  • asd
pervasive developmental disorder
  • pervasive development disorder
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CMC1_HUMAN
  • Epileptic encephalopathy, early infantile, 39 (EIEE39) [MIM:612949]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE39 is characterized by global hypomyelination of the central nervous system, with the gray matter appearing relatively unaffected. Inheritance is autosomal recessive. {ECO:0000269 PubMed:19641205, ECO:0000269 PubMed:24515575}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SLC25A12

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SLC25A12: view

No data available for Genatlas for SLC25A12 Gene

Publications for SLC25A12 Gene

  1. Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (PMID: 11566871) Palmieri L … Palmieri F (The EMBO journal 2001) 2 3 4 23 56
  2. AGC1 deficiency associated with global cerebral hypomyelination. (PMID: 19641205) Wibom R … Wedell A (The New England journal of medicine 2009) 3 4 23 56
  3. Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene. (PMID: 17151801) Correia C … Vicente AM (Journal of autism and developmental disorders 2006) 3 26 43 56
  4. Assignment of the SLC25A12 gene coding for the human calcium-binding mitochondrial solute carrier protein aralar to human chromosome 2q24. (PMID: 10702666) Crackower MA … Scherer SW (Cytogenetics and cell genetics 1999) 2 3 23 56
  5. Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain. (PMID: 9722566) del Arco A … Satrústegui J (The Journal of biological chemistry 1998) 2 3 4 56

Products for SLC25A12 Gene

Sources for SLC25A12 Gene