SLC25A12

Summary

Gene Symbol: SLC25A12
Description: solute carrier family 25 member 12
Alias: AGC1, ARALAR, EIEE39, calcium-binding mitochondrial carrier protein Aralar1, araceli hiperlarga, calcium binding mitochondrial carrier superfamily member Aralar1, mitochondrial aspartate glutamate carrier 1, solute carrier family 25 (aspartate/glutamate carrier), member 12, solute carrier family 25 (mitochondrial carrier, Aralar), member 12
Species: human
Products:     SLC25A12

Top Publications

  1. Rabionet R, McCauley J, Jaworski J, Ashley Koch A, Martin E, Sutcliffe J, et al. Lack of association between autism and SLC25A12. Am J Psychiatry. 2006;163:929-31 pubmed
    ..Multiple genomic screens have shown evidence suggesting linkage to chromosome 2q31-q33, which includes the SLC25A12 gene...
  2. Ramoz N, Cai G, Reichert J, Silverman J, Buxbaum J. An analysis of candidate autism loci on chromosome 2q24-q33: evidence for association to the STK39 gene. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1152-8 pubmed publisher
    ..using a set of 109 additional gene-oriented SNPs in this interval we observed that several SNPs encompassing the SLC25A12 gene provided the maximum evidence for linkage (NPL = 3.32, P = 0.0003)...
  3. Kobayashi K, Sinasac D, Iijima M, Boright A, Begum L, Lee J, et al. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet. 1999;22:159-63 pubmed
  4. Wibom R, Lasorsa F, Tohonen V, Barbaro M, Sterky F, Kucinski T, et al. AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med. 2009;361:489-95 pubmed publisher
    ..and seizures in a child with a homozygous missense mutation in the solute carrier family 25, member 12, gene SLC25A12, which encodes the AGC1 protein. Functional analysis of the mutant AGC1 protein showed abolished activity...
  5. Turunen J, Rehnstrom K, Kilpinen H, Kuokkanen M, Kempas E, Ylisaukko Oja T. Mitochondrial aspartate/glutamate carrier SLC25A12 gene is associated with autism. Autism Res. 2008;1:189-92 pubmed publisher
    Two single nucleotide polymorphisms (SNP) within Mitochondrial Aspartate/Glutamate Carrier SLC25A12 gene have recently shown to be strongly associated with autism...
  6. Marmol P, Pardo B, Wiederkehr A, del Arco A, Wollheim C, Satrustegui J. Requirement for aralar and its Ca2+-binding sites in Ca2+ signal transduction in mitochondria from INS-1 clonal beta-cells. J Biol Chem. 2009;284:515-24 pubmed publisher
    b>Aralar, the mitochondrial aspartate-glutamate carrier present in beta-cells, is a component of the malate-aspartate NADH shuttle (MAS). MAS is activated by Ca2+ in mitochondria from tissues with aralar as the only AGC isoform with an S0...
  7. Lepagnol Bestel A, Maussion G, Boda B, Cardona A, Iwayama Y, Delezoide A, et al. SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects. Mol Psychiatry. 2008;13:385-97 pubmed publisher
    ..Genome screens have provided evidence of linkage to chromosome 2q31-q33, which includes the SLC25A12 gene...
  8. Segurado R, Conroy J, Meally E, Fitzgerald M, Gill M, Gallagher L. Confirmation of association between autism and the mitochondrial aspartate/glutamate carrier SLC25A12 gene on chromosome 2q31. Am J Psychiatry. 2005;162:2182-4 pubmed
    ..a highly significant association between autism and a two-single-nucleotide-polymorphism haplotype in the SLC25A12 gene, with a homozygote genotype relative risk between 2.4 and 4.8...
  9. Blasi F, Bacchelli E, Carone S, Toma C, Monaco A, Bailey A, et al. SLC25A12 and CMYA3 gene variants are not associated with autism in the IMGSAC multiplex family sample. Eur J Hum Genet. 2006;14:123-6 pubmed
    ..Recently, significant association with autism has been reported for single-nucleotide polymorphisms (SNPs) in the SLC25A12 and CMYA3 genes on chromosome 2q...

More Information

Publications45

  1. Del Arco A, Satrustegui J. Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain. J Biol Chem. 1998;273:23327-34 pubmed
    ..A member of this subfamily (that we have termed Aralar) was cloned from a human heart cDNA library...
  2. Correia C, Coutinho A, Diogo L, Grazina M, Marques C, Miguel T, et al. Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene. J Autism Dev Disord. 2006;36:1137-40 pubmed
    ..We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene (SLC25A12) in mitochondrial dysfunction associated with autism...
  3. Chien W, Wu Y, Gau S, Huang Y, Soong W, Chiu Y, et al. Association study of the SLC25A12 gene and autism in Han Chinese in Taiwan. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:189-92 pubmed publisher
    ..Several studies reported that the solute carrier family 25 member A12 (SLC25A12) gene was associated with autism...
  4. Silverman J, Buxbaum J, Ramoz N, Schmeidler J, Reichenberg A, Hollander E, et al. Autism-related routines and rituals associated with a mitochondrial aspartate/glutamate carrier SLC25A12 polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2008;147:408-10 pubmed
    ..nucleotide polymorphisms (SNPs), rs2056202 and rs2292813, in the mitochondrial aspartate/glutamate carrier (SLC25A12) gene led us to ask whether any of the four previously identified familial traits in autism spectrum disorders (..
  5. Palmieri L, Pardo B, Lasorsa F, Del Arco A, Kobayashi K, Iijima M, et al. Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 2001;20:5060-9 pubmed
    ..These results show that the aspartate/glutamate carrier is regulated by Ca(2+) through a mechanism independent of Ca(2+) entry into mitochondria, and suggest a novel mechanism of Ca(2+) regulation of the aspartate/malate shuttle...
  6. Ramoz N, Reichert J, Smith C, Silverman J, Bespalova I, Davis K, et al. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am J Psychiatry. 2004;161:662-9 pubmed
    ..showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1)...
  7. Falk M, Li D, Gai X, McCormick E, Place E, Lasorsa F, et al. AGC1 Deficiency Causes Infantile Epilepsy, Abnormal Myelination, and Reduced N-Acetylaspartate. JIMD Rep. 2014;14:77-85 pubmed publisher
    ..A novel SLC25A12 homozygous missense mutation, c.1058G>A; p.Arg353Gln, segregated with disease in this kindred...
  8. Ola M, LaNoue K. Molecular basis for increased lactate formation in the Müller glial cells of retina. Brain Res Bull. 2018;144:158-163 pubmed publisher
    ..We investigated the expression and localization of AGC and its isoforms (aralar and citrin) in the intact rat retina...
  9. Wishart T, Paterson J, Short D, Meredith S, Robertson K, Sutherland C, et al. Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Mol Cell Proteomics. 2007;6:1318-30 pubmed
  10. Contreras L. Role of AGC1/aralar in the metabolic synergies between neuron and glia. Neurochem Int. 2015;88:38-46 pubmed publisher
    ..This review will consider the cellular distribution of the mitochondrial aspartate-glutamate carrier, aralar/AGC1/SLC25A12, and its role in the synergic metabolism between neurons and astrocytes.
  11. Llorente Folch I, Rueda C, Pardo B, Szabadkai G, Duchen M, Satrustegui J. The regulation of neuronal mitochondrial metabolism by calcium. J Physiol. 2015;593:3447-62 pubmed publisher
    ..The aspartate-glutamate exchanger Aralar/AGC1 (Slc25a12), a component of the malate-aspartate shuttle (MAS), is stimulated by modest increases in cytosolic Ca(2+) and ..
  12. Infantino V, Dituri F, Convertini P, Santarsiero A, Palmieri F, Todisco S, et al. Epigenetic upregulation and functional role of the mitochondrial aspartate/glutamate carrier isoform 1 in hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis. 2019;1865:38-47 pubmed publisher
    ..Aspartate-glutamate carrier isoform 1 (AGC1), encoded by SLC25A12 gene, catalyzes an exchange between intramitochondrial aspartate and cytosolic glutamate plus a proton across the ..
  13. Pronicka E, Piekutowska Abramczuk D, Ciara E, Trubicka J, Rokicki D, Karkucinska Wieckowska A, et al. New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre. J Transl Med. 2016;14:174 pubmed publisher
    ..MTND3, MTND5, NAXE, NDUFS6, NDUFS7, NDUFV1, OPA1, PARS2, PC, PDHA1, POLG, RARS2, RRM2B, SCO2, SERAC1, SLC19A3, SLC25A12, TAZ, TMEM126B, VARS2) were identified...
  14. Juaristi I, Garcia Martin M, Rodrigues T, Satrustegui J, Llorente Folch I, Pardo B. ARALAR/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of neuronal mitochondrial respiration, does not produce a primary increase in brain lactate. J Neurochem. 2017;142:132-139 pubmed publisher
    b>ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS)...
  15. Llorente Folch I, Rueda C, Pérez Liébana I, Satrustegui J, Pardo B. L-Lactate-Mediated Neuroprotection against Glutamate-Induced Excitotoxicity Requires ARALAR/AGC1. J Neurosci. 2016;36:4443-56 pubmed publisher
    ARALAR/AGC1/Slc25a12, the aspartate-glutamate carrier from brain mitochondria, is the regulatory step in the malate-aspartate NADH shuttle, MAS...
  16. Sasagawa S, Nishimura Y, Koiwa J, Nomoto T, Shintou T, Murakami S, et al. In Vivo Detection of Mitochondrial Dysfunction Induced by Clinical Drugs and Disease-Associated Genes Using a Novel Dye ZMJ214 in Zebrafish. ACS Chem Biol. 2016;11:381-8 pubmed publisher
    ..Live imaging of zebrafish stained with ZMJ214 also revealed that knock-down of slc25a12, a mitochondrial carrier protein associated with autism, dysregulated the mitochondrial membrane potential...
  17. Wang C, Zhang J, Zhang M, Chen H, Ying W. Aralar plays a significant role in maintaining the survival and mitochondrial membrane potential of BV2 microglia. Int J Physiol Pathophysiol Pharmacol. 2015;7:107-14 pubmed
    ..b>Aralar/AGC1, a Ca(2+)-dependent aspartate-glutamate carrier on mitochondrial membrane, is a component of MAS...
  18. Contreras L, Rial E, Cerdan S, Satrustegui J. Uncoupling Protein 2 (UCP2) Function in the Brain as Revealed by the Cerebral Metabolism of (1-13C)-Glucose. Neurochem Res. 2017;42:108-114 pubmed publisher
    The mitochondrial aspartate/glutamate transporter Aralar/AGC1/Slc25a12 is critically involved in brain aspartate synthesis, and AGC1 deficiency results in a drastic fall of brain aspartate levels in humans and mice...
  19. Porcelli V, Longo A, Palmieri L, Closs E, Palmieri F. Asymmetric dimethylarginine is transported by the mitochondrial carrier SLC25A2. Amino Acids. 2016;48:427-36 pubmed publisher
    ..arginine, lysine, and ornithine and in contrast to the other known mitochondrial amino acid transporters SLC25A12, SLC25A13, SLC25A15, SLC25A18, SLC25A22, and SLC25A29...
  20. Sanz R, Del Arco A, Ayuso C, Ramos C, Satrustegui J. Assignment of the calcium-binding mitochondrial carrier Aralar1 gene (SLC25A12) to human chromosome band 2q31 by in situ hybridization. Cytogenet Cell Genet. 2000;89:143-4 pubmed
  21. Xu W, Liu L, Hornby D. c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-α pathway to PCSK9-mediated LDLR degradation pathway. Molecules. 2012;17:12086-101 pubmed publisher
    ..The novel pathway described here will open new avenues for exploring novel disease treatments. ..
  22. Satrustegui J, Contreras L, Ramos M, Marmol P, del Arco A, Saheki T, et al. Role of aralar, the mitochondrial transporter of aspartate-glutamate, in brain N-acetylaspartate formation and Ca(2+) signaling in neuronal mitochondria. J Neurosci Res. 2007;85:3359-66 pubmed
    ..Disrupting the gene for aralar, SLC25a12, in mice has enabled the discovery of two new roles of this carrier...
  23. Amoedo N, Punzi G, Obre E, Lacombe D, De Grassi A, Pierri C, et al. AGC1/2, the mitochondrial aspartate-glutamate carriers. Biochim Biophys Acta. 2016;1863:2394-412 pubmed publisher
    In this review we discuss the structure and functions of the aspartate/glutamate carriers (AGC1-aralar and AGC2-citrin)...
  24. Napolioni V, Persico A, Porcelli V, Palmieri L. The mitochondrial aspartate/glutamate carrier AGC1 and calcium homeostasis: physiological links and abnormalities in autism. Mol Neurobiol. 2011;44:83-92 pubmed publisher
    ..b>SLC25A12, an ASD susceptibility gene, encodes the Ca(2+)-regulated mitochondrial aspartate-glutamate carrier, isoform 1 (..
  25. Liu J, Yang A, Zhang Q, Yang G, Yang W, Lei H, et al. Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2015;168B:236-46 pubmed publisher
    The solute carrier family 25 (aspartate/glutamate carrier), member 12 gene (SLC25A12) has been strongly posed as a candidate gene for autism spectrum disorder (ASD) given its important role in mitochondrial function and adenosine ..
  26. Aoki Y, Cortese S. Mitochondrial Aspartate/Glutamate Carrier SLC25A12 and Autism Spectrum Disorder: a Meta-Analysis. Mol Neurobiol. 2016;53:1579-1588 pubmed publisher
    ..Studies investigating the possible association between ASD and polymorphism in SLC25A12, which encodes the mitochondrial aspartate/glutamate carrier, have yielded inconsistent results...
  27. Rubi B, del Arco A, Bartley C, Satrustegui J, Maechler P. The malate-aspartate NADH shuttle member Aralar1 determines glucose metabolic fate, mitochondrial activity, and insulin secretion in beta cells. J Biol Chem. 2004;279:55659-66 pubmed
    ..7 mm glucose (+65%, p < 0.05) compared with controls. These results show that aspartate-glutamate carrier capacity limits glucose-stimulated insulin secretion and that Aralar1 overexpression enhances mitochondrial metabolism. ..
  28. Crackower M, Sinasac D, Lee J, Herbrick J, Tsui L, Scherer S. Assignment of the SLC25A12 gene coding for the human calcium-binding mitochondrial solute carrier protein aralar to human chromosome 2q24. Cytogenet Cell Genet. 1999;87:197-8 pubmed
  29. Satrustegui J, Pardo B, del Arco A. Mitochondrial transporters as novel targets for intracellular calcium signaling. Physiol Rev. 2007;87:29-67 pubmed
    ..The two mammalian AGCs, aralar and citrin, are members of the malate-aspartate NADH shuttle, and citrin, the liver AGC, is also a member of the ..
  30. Thangaratnarajah C, Ruprecht J, Kunji E. Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. Nat Commun. 2014;5:5491 pubmed publisher
    ..These structures provide a framework for understanding cases of the mitochondrial disease citrin deficiency. ..
  31. Kim S, Silva R, Flores C, Jacob S, Guter S, Valcante G, et al. A quantitative association study of SLC25A12 and restricted repetitive behavior traits in autism spectrum disorders. Mol Autism. 2011;2:8 pubmed publisher
    b>SLC25A12 was previously identified by a linkage-directed association analysis in autism...
  32. Liu Y, Pu Q, Wu M, Yu C. Proteomic analysis for the impact of hypercholesterolemia on expressions of hepatic drug transporters and metabolizing enzymes. Xenobiotica. 2016;46:940-7 pubmed publisher
    ..Among those, protein levels of hepatic drug transporters (MRP2, ABCD3, OAT2, SLC25A12, SCL38A3, SLC2A2 and SLC25A5) and metabolizing enzymes (CYP2B3, CYP2C7, CYP2C11, CYP2C13, CYP4A2 and UGT2B) were ..
  33. Palmieri L, Papaleo V, Porcelli V, Scarcia P, Gaita L, Sacco R, et al. Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1. Mol Psychiatry. 2010;15:38-52 pubmed publisher
    ..Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and ..
  34. Hong C, Liou Y, Liao D, Hou S, Yen F, Tsai S. Association study of polymorphisms in the mitochondrial aspartate/glutamate carrier SLC25A12 (aralar) gene with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1510-3 pubmed
    ..Aralar is encoded by the SLC25A12 gene...
  35. Liu J, Mo W, Zhang Z, Yu H, Yang A, Qu F, et al. Single Nucleotide Polymorphisms in SLC19A1 and SLC25A9 Are Associated with Childhood Autism Spectrum Disorder in the Chinese Han Population. J Mol Neurosci. 2017;62:262-267 pubmed publisher
    ..of this study was to determine the association between single nucleotide polymorphisms (SNPs) in SLC19A1 and SLC25A12 genes with childhood ASD in a Chinese Han population...
  36. Wohlrab H. The human mitochondrial transport protein family: identification and protein regions significant for transport function and substrate specificity. Biochim Biophys Acta. 2005;1709:157-68 pubmed
    ..The sum of subfamilies in the 12 subsets was lowest for the phosphate transport protein (PTP) and highest for aralar 1. Transmembrane sequences are most unique. Sequence similarities are highest near the membrane center and matrix...