geno logo
     HELP     Sign In

Quick Links

TOOLS
Search

Relevance to Autism

Several studies have found genetic association between the SLC25A12 gene and autism in SARC, AGRE and Irish population cohorts. However, several studies found no genetic association between the SLC25A12 gene and autism in IMGSAC, Chinese Han, Caucasian-American and Portuguese population cohorts.

Molecular Function

The encoded protein has solute:cation symporter activity.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism.
ASD
Positive Association
Autism-related routines and rituals associated with a mitochondrial aspartate/glutamate carrier SLC25A12 polymorphism.
ASD subphenotype
Restricted and repetitive behaviors
Positive Association
Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta-analysis.
ASD
Positive Association
Confirmation of association between autism and the mitochondrial aspartate/glutamate carrier SLC25A12 gene on chromosome 2q31.
ASD
Positive Association
Mitochondrial Aspartate/Glutamate Carrier SLC25A12 and Autism Spectrum Disorder: a Meta-Analysis.
ASD
Positive Association
Single nucleotide polymorphism rs6716901 in SLC25A12 gene is associated with Asperger syndrome.
ASD
Asperger syndrome
Positive Association
A quantitative association study of SLC25A12 and restricted repetitive behavior traits in autism spectrum disorders.
Restricted and repetitive behaviors (measured by R
Positive Association
Mitochondrial aspartate/glutamate carrier SLC25A12 gene is associated with autism.
ASD
Positive Association
An analysis of candidate autism loci on chromosome 2q24-q33: evidence for association to the STK39 gene.
ASD
Positive Association
ASD
Negative Association
The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families.
ASD
Negative Association
Association study of the SLC25A12 gene and autism in Han Chinese in Taiwan.
ASD
Negative Association
Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutam...
ASD
Negative Association
Lack of association between autism and SLC25A12.
ASD
Negative Association
SLC25A12 and CMYA3 gene variants are not associated with autism in the IMGSAC multiplex family sample.
ASD
Support
Brain region-specific altered expression and association of mitochondria-related genes in autism.
ASD
Support
Epilepsy/seizures
Support
SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population
DD, epilepsy/seizures
Support
De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
ID, epilepsy/seizures
Support
Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Highly Cited
Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain.
Recent Recommendation
In Vivo Detection of Mitochondrial Dysfunction Induced by Clinical Drugs and Disease-Associated Genes Using a Novel Dye ZMJ214 in Zebrafish.
Recent Recommendation
SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects.
Recent Recommendation
Role of aralar, the mitochondrial transporter of aspartate-glutamate, in brain N-acetylaspartate formation and Ca(2) signaling in neuronal mitocho...
Recent Recommendation
Essential role of aralar in the transduction of small Ca2 signals to neuronal mitochondria.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN232R001 
 frameshift_variant 
 c.2016del 
 p.Ala673GlnfsTer19 
 Familial 
 Paternal 
 Multiplex 
 GEN232R002a 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN232R003a 
 missense_variant 
 c.832T>C 
 p.Tyr278His 
 Familial 
 Both parents 
  
 GEN232R004a 
 missense_variant 
 c.1469G>A 
 p.Arg490Gln 
 Familial 
 Both parents 
  
  et al.  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN232C001 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 SARC, AGRE 
 Discovery 
 GEN232C002 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 SARC, AGRE 
 Discovery 
 GEN232C003 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 Irish 
 Replication 
 GEN232C004 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 Irish 
 Replication 
 GEN232C005 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 SARC, AGRE 
 Replication 
 GEN232C006 
 intron_variant 
 rs6716901 
 c.931-1741C>T;c.880-1741C>T;c.610-1741C>T 
  
 117 individuals with Asperger syndrome and 426 controls (all of Caucasian ancestry) 
 Discovery 
 GEN232C007 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 334 ASD families 
 Replication 
 GEN232C008 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 97 Finnish ASD families 
 Replication 
 GEN232C009 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 Meta-analysis of 7 datasets containing 2001 families 
 Replication (meta-analysis) 
 GEN232C010 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 Meta-analysis of 6 datasets containing 2016 families 
 Replication (meta-analysis) 
 GEN232C011 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 Meta-analysis of a total of 775 ASD cases, 922 controls, and 1289 families from 8 studies 
 Replication (meta-analysis) 
 GEN232C012 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 Meta-analysis of 465 ASD cases, 450 controls, and 1516 families from 7 studies 
 Replication (meta-analysis) 
 GEN232C013 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 179 ASD probands from the UIC-UF samples 
 Replication 
 GEN232C014 
 intron_variant 
 rs2056202 
 c.210-21A>G;c.159-21A>G;c.5-11462A>G 
  
 720 ASD probands from the Simons Simplex Collection (SSC) 
 Replication 
 GEN232C015 
 intron_variant 
 rs908670 
 c.845+293A>G;c.794+293A>G;c.524+293A>G;c.572+293A>G 
  
 720 ASD probands from the Simons Simplex Collection (SSC) 
 Discovery 
 GEN232C016 
 intron_variant 
 rs2292813 
 c.1745-58A>G;c.1694-58A>G;c.1424-58A>G 
  
 249 ASD probands and 353 healthy controls from the Chinese Han population 
 Replication 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
2
Duplication
 1
 
2
Duplication
 1
 
2
Deletion
 3
 
2
Deletion
 1
 
2
Deletion-Duplication
 16
 
2
Deletion
 1
 

Model Summary

Impaired motor functions with myelination defects.

References

Type
Title
Author, Year
Primary
Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type mitochondrial aspartate-glutamate carrier.
Additional
Slc25a12 disruption alters myelination and neurofilaments: a model for a hypomyelination syndrome and childhood neurodevelopmental disorders.

M_SLC25A12_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Gene trap vector inserted into Exon 13 of the Slc25a12 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: C57BL
Genetic Background: C57BL/6; 129SvEvBrd
ES Cell Line: SVJ129
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SLC25A12_2_KO_HT

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Gene trap vector inserted into Exon 13 of the Slc25a12 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: C57BL
Genetic Background: C57BL/6; 129SvEvBrd
ES Cell Line: SVJ129
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SLC25A12_3_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted replacement of exon 1 with neo-resistance/GFP cassette.
Allele Type: Targeted (Knock out)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6Tac
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SLC25A12_4_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted replacement of exon 1 with neo-resistance/GFP cassette.
Allele Type: Targeted (Knock out)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6Tac
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SLC25A12_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Grip strength1
Decreased
Description: Decreased grip strength
Exp Paradigm: Wire hanging test
 Wire hang test
 Unreported
Motor coordination and balance1
Decreased
Description: Decreased muscle coordination
Exp Paradigm: Bar test for balance coordination and neuromuscular strength
 Balance beam test
 Unreported
Hunched posture1
Decreased
Description: Display hunched posture
Exp Paradigm: General observations
 General observations
 Unreported
Myelination1
Decreased
Description: Decreased myelination
Exp Paradigm: Histological analysis of myelin stain
 Histology
 Unreported
Myelination1
Decreased
Description: Decreased galactocerebroside, a major myelin specific lipid expression
Exp Paradigm: High-performance thin-layer chromatography and quantification
 High-performance thin-layer chromatography
 Unreported
Myelination1
Decreased
Description: Decreased myelination
Exp Paradigm: Immunocytochemical study using antibody to the mbp
 Immunocytochemistry
 Unreported
Brain bioactive compound levels: n-acetylaspartate1
Decreased
Description: Decreased n-acetylaspartate amount
Exp Paradigm: Column extraction followed by hplc
 High-performance liquid chromatography (hplc)
 Unreported
Respiratory function1
Decreased
Description: Decrease in respiratory rate
Exp Paradigm: Clark type oxygen electrode in mitochondrial fractions with glutamate + malate as substrate
 Mitochondrial oxygen consumption studies
 Unreported
Size/growth1
Decreased
Description: Decreased growth
Exp Paradigm: General observations
 General observations
 Unreported
Gene expression1
Decreased
Description: Decreased aralar gene expression
Exp Paradigm: Gene expression
 Northern blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased protein expression
Exp Paradigm: Protein expression
 Western blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased mylein specific protein: mbp and mobp expression
Exp Paradigm: Protein expression
 Western blot
 Unreported
Protein expression level evidence1
 No change
 Western blot
 Unreported
Brain morphology1
 No change
 Histology
 Unreported
Respiratory function1
 No change
 Mitochondrial oxygen consumption studies
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_SLC25A12_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Respiratory function1
Decreased
Description: Decrease in respiratory rate
Exp Paradigm: Clark type oxygen electrode in mitochondrial fractions with glutamate + malate as substrate
 Mitochondrial oxygen consumption studies
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased aralar protein expression
Exp Paradigm: Protein expression
 Western blot
 Unreported
Size/growth1
 No change
 General observations
 Unreported
Gene expression1
 No change
 Northern blot
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_SLC25A12_3_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain cytoarchitecture1
Decreased
Description: Decreased number of myelin basic protein fibers in corpus callosum, anterior commissure, internal capsule, habenulointerpeduncular tract
Exp Paradigm: Immunohistochemical analysis using proteolipid protein staining
 Immunohistochemistry
 P13-p14
Morphology and size of the corpus callosum1
Abnormal
Description: Abnormal neuronal integrity indicated by disrupted alignment of purkinje cell layer with less elaborate purkinje cell denrites and thinner molecular layer
Exp Paradigm: Calbindin immunostaining analysis of cerebellum
 Immunohistochemistry
 Unreported
Morphology and size of the corpus callosum1
Abnormal
Description: Abnormal neuronal integrity indicated by comparable large fiber tracts in corpus callosum but decreased neuronal processes present in layer iv to vi
Exp Paradigm: Immunohistochemical analysis on brains for nf triplet proteins
 Immunohistochemistry
 P13-p14
Brain size1
Decreased
Description: Decreased brain size in all brain structures including hippocampus, striatum, and thalamus
Exp Paradigm: Cresyl violet and hematoxylin-eosin staining
 Histology
 P13-p14
Mortality/lethality1
Increased
Description: Increased lethality with no mice surviving by 4 weeks
Exp Paradigm: General observations
 General observations
 3 weeks
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory demonstrated by wide-based ataxic gait, as well as tremor
Exp Paradigm: General observations
 General observations
 Unreported
Size/growth1
Decreased
Description: Decreased size indicative of growth retardation
Exp Paradigm: General observations
 General observations
 P7
Protein expression level evidence1
Decreased
Description: Decreased protein expression of myelin basic protein
Exp Paradigm: Protein expression
 Western blot
 P10
General characteristics1
 No change
 General observations
 P6
Protein expression level evidence1
 No change
 Western blot
 P10
Brain morphology1
 No change
 Histology
 P13-p14
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_SLC25A12_4_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Gene expression1
Decreased
Description: Decreased expression of mag
Exp Paradigm: Gene expression
 Quantitative pcr (qrt-pcr)
 Unreported
Size/growth1
 No change
 General observations
 P7
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 Unreported
Brain morphology1
 No change
 Magnetic resonance imaging (mri)
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior





Download SLC25A12's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
C20orf24 chromosome 20 open reading frame 24 55969 Q9BUV8 LC-MS/MS
LC/ESI/MS/MS
Ewing RM , et al. 2007
CHCHD6 coiled-coil-helix-coiled-coil-helix domain containing 6 84303 Q9BRQ6 LC-MS/MS
Havugimana PC , et al. 2012
FBXO6 F-box only protein 6 26270 Q9NRD1 IP; LC-MS/MS
Liu B , et al. 2012
FMR1 fragile X mental retardation 1 2332 G8JLE9 PAR-CLIP
Ascano M Jr , et al. 2012
GNAS Neuroendocrine secretory protein 55 2778 O95467 LC-MS/MS
Havugimana PC , et al. 2012
PELO pelota homolog (Drosophila) 53918 Q9BRX2 LC-MS/MS
LC/ESI/MS/MS
Ewing RM , et al. 2007
PHLDA3 pleckstrin homology-like domain, family A, member 3 23612 Q9Y5J5 LC-MS/MS
LC/ESI/MS/MS
Ewing RM , et al. 2007
PNKP polynucleotide kinase 3'-phosphatase 11284 Q96T60 LC-MS/MS
LC/ESI/MS/MS
Ewing RM , et al. 2007
SLC25A13 solute carrier family 25 (aspartate/glutamate carrier), member 13 10165 Q9UJS0 IP; LC-MS/MS
Huttlin EL , et al. 2015
UBC ubiquitin C 7316 P63279 MS
Wagner SA , et al. 2011
UBE3A ubiquitin protein ligase E3A 7337 Q05086 IP; MS; COMPASS
Martnez-Nol G , et al. 2012

HELP
Copyright © 2017 MindSpec, Inc.