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Relevance to Autism

Genetic association has been found between the ATP2B2 gene and autism in a combined AGRE, ISART (Italian) and US cohort (Carayol et al., 2011). A de novo missense variant that was predicted to be damaging was identified in the ATP2B2 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014, and two de novo nonsense variants in this gene were observed in ASD probands from Japanese trios in Takata et al., 2018. TADA analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as the Japanese ASD cohort from Takata et al., 2018, identified ATP2B2 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Molecular Function

This gene encodes the plasma membrane calcium ATPase isoform 2. The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Converging evidence for an association of ATP2B2 allelic variants with autism in male subjects.
ASD
Positive Association
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...
ASD, SCZ
Positive Association
The evidence for association of ATP2B2 polymorphisms with autism in Chinese Han population.
ASD
Positive Association
The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families.
ASD
Support
Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder.
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Recent Recommendation
Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.
ASD
Recent Recommendation
Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN273R001 
 missense_variant 
 c.2453C>T 
 p.Thr818Met 
 De novo 
 NA 
 Simplex 
 GEN273R002 
 intron_variant 
 c.2511+26G>A 
  
 De novo 
 NA 
  
 GEN273R003 
 intron_variant 
 c.1043-19C>T 
  
 De novo 
 NA 
  
 GEN273R004 
 synonymous_variant 
 c.2757G>A 
 p.Thr919%3D 
 De novo 
 NA 
 Simplex 
 GEN273R005 
 stop_gained 
 c.3191G>A 
 p.Trp1064Ter 
 De novo 
 NA 
 Simplex 
 GEN273R006 
 stop_gained 
 c.2268C>A 
 p.Cys756Ter 
 De novo 
 NA 
 Simplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN273C001 
 intron_variant 
 rs3774180 
 c.2136+3387A>G;c.2001+3387A>G;c.2043+3387A>G;c.2103+3387A>G 
 N/A 
 AGRE, ISART (Italian), US 
 Discovery 
 GEN273C002 
 intron_variant 
 rs2278556 
 c.1660-296C>T;c.1525-296C>T;c.1567-296C>T;c.1627-296C>T 
 N/A 
 AGRE, ISART (Italian), US 
 Discovery 
 GEN273C003 
 intron_variant 
 rs241509 
 c.2703+9G>T;c.2568+9G>T;c.2610+9G>T;c.2670+9G>T 
  
 AGRE, ISART (Italian), US 
 Discovery 
 GEN273C004 
 synonymous_variant 
 rs35678 
 c.3357G>A;c.3222G>A;c.3264G>A;c.3324G>A 
 p.(=) 
 Italian Autism Network (ITAN) 
 Discovery 
 GEN273C005 
 intron_variant 
 rs3774179 
 c.2136+3306A>G;c.2001+3306A>G;c.2043+3306A>G;c.2103+3306A>G 
 C/T 
 427 ASD trios of Han Chinese descent 
 Discovery 
 GEN273C006 
 intron_variant 
 rs7619385 
 c.1417-1174C>T;c.1282-1174C>T;c.1324-1174C>T 
  
 7387 ASD cases and 8567 controls from Autism Center of Excellence Network (ACE), Autism Genetic Resource Exchange (AGRE), Autism Genome Project (AGP), Finnish Case-Control ASD Collection, NIMH Repository and Montreal/Boston (MonBos) Collection, Population-Based Autism Genetics and Environment Study (PAGES), Simons Simplex Collection (SSC), and Weiss Laboratory Autism Collection 
 Discovery 
 GEN273C007 
 intron_variant 
 rs9879311 
 c.1417-1608G>A;c.1282-1608G>A;c.1324-1608G>A 
  
 ASD and schizophrenia GWAS data from the Psychiatric Genomics Consortium (PGC) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Deletion-Duplication
 19
 
3
Deletion
 1
 
3
Deletion
 1
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Deletion
 2
 

Model Summary

Importance of PMCA2 in calcium signaling, glutamate receptor expression and survival of Purkinje cells.

References

Type
Title
Author, Year
Primary
Purkinje cell dysfunction and delayed death in plasma membrane calcium ATPase 2-heterozygous mice.

M_ATP2B2_1_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted disruption of exon 19 which encodes transmembrane domains essential for transport activity of Atp2b2.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_ATP2B2_1_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: ampa receptors1
Decreased
Description: Decreased GluR2/3 immunoreactivity in Purkinje cells from cerebellar sections
Exp Paradigm: Immunoblotting analysis of GluR2/3 from cerebellar sections
 Western blot
 Unreported
Neuronal number: purkinje cells1
Decreased
Description: Decreased Purkinje cell numbers in cerebellum
Exp Paradigm: Stereological cell counts of cerebellum slices
 Stereology
 4.5 months
Protein expression level evidence1
Decreased
Description: Decreased protein levels of GluR2/3 and mGluR1 in cerebellum
Exp Paradigm: Glutamate Receptor Expression
 Western blot
 8 weeks
Gene expression1
Decreased
Description: Decreased levels of GluR2, GluR3 and mGluR1 transcript in cerebellum
Exp Paradigm: Glur2/3, Mglur1 Transcript Levels
 Quantitative pcr (qrt-pcr)
 8 weeks
Protein expression level evidence1
 No change
 Western blot
 3 weeks
Protein expression level evidence1
 No change
 Western blot
 8 weeks
Brain cytoarchitecture1
 No change
 Stereology
 8, 20 weeks
Neuronal number: purkinje cells1
 No change
 Stereology
 8 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ABCB9 ADORA2A 23457 Q9NP78 IP; LC-MS/MS
Huttlin EL , et al. 2015
ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 89845 Q5T3U5 IP; LC-MS/MS
Huttlin EL , et al. 2015
ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 10257 O15439 IP; LC-MS/MS
Huttlin EL , et al. 2015
ABCD1 AGBL4 215 P33897 IP; LC-MS/MS
Huttlin EL , et al. 2015
ABCD4 ATP-binding cassette sub-family D member 4 5826 O14678 IP; LC-MS/MS
Huttlin EL , et al. 2015
ADAMTS4 ASS1 9507 O75173 IP; LC-MS/MS
Huttlin EL , et al. 2015
ALG10 ALG10, alpha-1,2-glucosyltransferase 84920 Q5BKT4 IP; LC-MS/MS
Huttlin EL , et al. 2015
ALG8 ALG8, alpha-1,3-glucosyltransferase 79053 A6NDW6 IP; LC-MS/MS
Huttlin EL , et al. 2015
APOD Apolipoprotein D 347 P05090 IP; LC-MS/MS
Huttlin EL , et al. 2015
ARL6IP1 ADP-ribosylation factor-like 6 interacting protein 1 23204 Q15041 IP; LC-MS/MS
Huttlin EL , et al. 2015
ATG9A autophagy related 9A 79065 Q7Z3C6 IP; LC-MS/MS
Huttlin EL , et al. 2015
ATP2B3 Plasma membrane calcium-transporting ATPase 3 492 Q16720-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
ATP2B4 ATPase, Ca++ transporting, plasma membrane 4 493 P23634 IP; LC-MS/MS
Huttlin EL , et al. 2015
ATP9A ATPase, class II, type 9A 10079 O75110 IP; LC-MS/MS
Huttlin EL , et al. 2015
ATPBD4 diphthamine biosynthesis 6 NM_001141972 Q7L8W6 IP; LC-MS/MS
Huttlin EL , et al. 2015
AZGP1 Zinc-alpha-2-glycoprotein 563 P25311 IP; LC-MS/MS
Huttlin EL , et al. 2015
BCAP31 B-cell receptor-associated protein 31 10134 P51572 IP; LC-MS/MS
Huttlin EL , et al. 2015
BRP44 mitochondrial pyruvate carrier 2 NM_015415 A0A024R8Z5 IP; LC-MS/MS
Huttlin EL , et al. 2015
BTBD9 BTB (POZ) domain containing 9 114781 Q96Q07 IP; LC-MS/MS
Huttlin EL , et al. 2015
C12ORF49 chromosome 12 open reading frame 49 79794 Q9H741 IP; LC-MS/MS
Huttlin EL , et al. 2015
C4A complement component 4A (Rodgers blood group) 720 P0C0L4 IP; LC-MS/MS
Huttlin EL , et al. 2015
C6ORF72 glycoprotein integral membrane 1 116254 Q9NU53 IP; LC-MS/MS
Huttlin EL , et al. 2015
CD79B B-cell antigen receptor complex-associated protein beta chain 974 P40259-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
CD83 ITGB7 9308 Q01151 IP; LC-MS/MS
Huttlin EL , et al. 2015
CHSY1 chondroitin sulfate synthase 1 22856 Q86X52 IP; LC-MS/MS
Huttlin EL , et al. 2015
CLU clusterin 1191 P10909 IP; LC-MS/MS
Huttlin EL , et al. 2015
CYP2B6 Cytochrome P450 2B6 1555 P20813 IP; LC-MS/MS
Huttlin EL , et al. 2015
DGAT1 PCDHA13 8694 O75907 IP; LC-MS/MS
Huttlin EL , et al. 2015
DHRS7 Dehydrogenase/reductase SDR family member 7 51635 Q9Y394-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
DHRS9 Dehydrogenase/reductase SDR family member 9 10170 Q9BPW9 IP; LC-MS/MS
Huttlin EL , et al. 2015
DLG1 discs, large homolog 1 (Drosophila) 1739 Q12959 IP/WB; Y2H; GST
DeMarco SJ and Strehler EE 2001
DLG2 discs, large homolog 2 (Drosophila) 1740 Q15700 IP/WB; Y2H; GST
DeMarco SJ and Strehler EE 2001
DLG4 DLG4discs, large homolog 4 (Drosophila) 1742 P78352 IP/WB; Y2H; GST
DeMarco SJ and Strehler EE 2001
EDNRB Endothelin B receptor 1910 P24530-3 IP; LC-MS/MS
Huttlin EL , et al. 2015
EFNB2 ephrin-B2 1948 P52799 IP; LC-MS/MS
Huttlin EL , et al. 2015
ENTPD7 ectonucleoside triphosphate diphosphohydrolase 7 57089 Q9NQZ7 IP; LC-MS/MS
Huttlin EL , et al. 2015
ERBB2IP erbb2 interacting protein 55914 Q96RT1 Inverted peptide arrays
Boisguerin P , et al. 2004
ERMP1 endoplasmic reticulum metallopeptidase 1 79956 B3KSB1 IP; LC-MS/MS
Huttlin EL , et al. 2015
FAM174A Membrane protein FAM174A 345757 Q8TBP5 IP; LC-MS/MS
Huttlin EL , et al. 2015
FAR2 fatty acyl CoA reductase 2 55711 Q96K12 IP; LC-MS/MS
Huttlin EL , et al. 2015
FPR2 N-formyl peptide receptor 2 2358 P25090 IP; LC-MS/MS
Huttlin EL , et al. 2015
FZD10 TYR 11211 Q6NSL8 IP; LC-MS/MS
Huttlin EL , et al. 2015
FZD7 frizzled family receptor 7 8324 O75084 IP; LC-MS/MS
Huttlin EL , et al. 2015
GALNT6 UBR7 11226 Q8NCL4 IP; LC-MS/MS
Huttlin EL , et al. 2015
GHDC GH3 domain-containing protein 84514 Q8N2G8-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
GLB1L2 Beta-galactosidase-1-like protein 2 89944 Q8IW92 IP; LC-MS/MS
Huttlin EL , et al. 2015
GOLGA5 golgin A5 9950 Q8TBA6 IP; LC-MS/MS
Huttlin EL , et al. 2015
GOLIM4 golgi integral membrane protein 4 27333 O00461 IP; LC-MS/MS
Huttlin EL , et al. 2015
GOLM1 golgi membrane protein 1 51280 B3KNK9 IP; LC-MS/MS
Huttlin EL , et al. 2015
GPR161 G protein-coupled receptor 161 23432 B7Z5Z6 IP; LC-MS/MS
Huttlin EL , et al. 2015
GPR89A Golgi pH regulator A 51463 B7ZAQ6-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
HSD17B6 17-beta-hydroxysteroid dehydrogenase type 6 8630 O14756 IP; LC-MS/MS
Huttlin EL , et al. 2015
HTR2C 5-hydroxytryptamine receptor 2C 3358 P28335 IP; LC-MS/MS
Huttlin EL , et al. 2015
HTR3A 5-hydroxytryptamine receptor 3A 3359 P46098-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
IL29 Interferon lambda-1 282618 Q8IU54 IP; LC-MS/MS
Huttlin EL , et al. 2015
LASS6 Ceramide synthase 6 253782 Q6ZMG9 IP; LC-MS/MS
Huttlin EL , et al. 2015
LCLAT1 lysocardiolipin acyltransferase 1 253558 Q6UWP7 IP; LC-MS/MS
Huttlin EL , et al. 2015
LEMD2 LEM domain containing 2 221496 Q8NC56 IP; LC-MS/MS
Huttlin EL , et al. 2015
LGALS8 Galectin-8 3964 O00214 IP; LC-MS/MS
Huttlin EL , et al. 2015
LILRB4 Leukocyte immunoglobulin-like receptor subfamily B member 4 11006 Q8NHJ6-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
LPAR4 Lysophosphatidic acid receptor 4 2846 Q99677 IP; LC-MS/MS
Huttlin EL , et al. 2015
MAOB Amine oxidase [flavin-containing] B 4129 P27338 IP; LC-MS/MS
Huttlin EL , et al. 2015
MUCL1 Mucin-like protein 1 118430 Q96DR8 IP; LC-MS/MS
Huttlin EL , et al. 2015
NOS3 nitric oxide synthase 3 (endothelial cell) 4846 P60323 IP/WB
Holton M , et al. 2010
NUFIP1 Nuclear FMRP Interacting Protein 1 26747 Q9UHK0 IP; LC-MS/MS
Huttlin EL , et al. 2015
OSTC oligosaccharyltransferase complex subunit (non-catalytic) 58505 Q9NRP0 IP; LC-MS/MS
Huttlin EL , et al. 2015
PCDHGB1 Protocadherin gamma-B1 56104 Q9Y5G3-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
PCNXL3 pecanex-like 3 (Drosophila) 399909 Q9H6A9 IP; LC-MS/MS
Huttlin EL , et al. 2015
PDZD11 PDZ domain containing 11 51248 Q5EBL8 IP/WB
Goellner GM , et al. 2003
PIGN phosphatidylinositol glycan anchor biosynthesis, class N 23556 O95427 IP; LC-MS/MS
Huttlin EL , et al. 2015
PIGO phosphatidylinositol glycan anchor biosynthesis, class O 84720 Q8TEQ8 IP; LC-MS/MS
Huttlin EL , et al. 2015
PPP3CA protein phosphatase 3, catalytic subunit, alpha isozyme 5530 Q08209 IP/WB
Holton M , et al. 2007
PRKCA protein kinase C, alpha 24680 Q9EP80 in vitro kinase assay
Baggaley E , et al. 2007
PTGFR Prostaglandin F2-alpha receptor 5737 P43088 IP; LC-MS/MS
Huttlin EL , et al. 2015
PTGIR Prostacyclin receptor 5739 P43119 IP; LC-MS/MS
Huttlin EL , et al. 2015
RAPGEF5 Rap guanine nucleotide exchange factor (GEF) 5 9771 A8MQ07 IP; LC-MS/MS
Huttlin EL , et al. 2015
RHOT2 ras homolog family member T2 89941 Q8IXI1 IP; LC-MS/MS
Huttlin EL , et al. 2015
SCARA3 Scavenger receptor class A member 3 51435 Q6AZY7-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
SDF4 stromal cell derived factor 4 51150 Q9BRK5 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC15A4 solute carrier family 15, member 4 121260 Q8N697 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC22A16 Solute carrier family 22 member 16 85413 Q86VW1 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC26A6 Solute carrier family 26 member 6 65010 Q9BXS9-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC2A5 solute carrier family 2 (facilitated glucose/fructose transporter), member 5 6518 P22732 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC38A9 Sodium-coupled neutral amino acid transporter 9 153129 Q8NBW4-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC45A2 Membrane-associated transporter protein 51151 D6RGY6 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC47A1 Multidrug and toxin extrusion protein 1 55244 Q96FL8-3 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC4A2 solute carrier family 4, anion exchanger, member 2 (erythrocyte membrane protein band 3-like 1) 6522 P04920 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC4A7 solute carrier family 4, sodium bicarbonate cotransporter, member 7 9497 B5M449 IP; LC-MS/MS
Huttlin EL , et al. 2015
SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2 9351 Q6NTG0 Y2H; GST; IP/WB
DeMarco SJ , et al. 2002
SNTA1 syntrophin, alpha 1 6640 Q13424 Inverted peptide arrays
Boisguerin P , et al. 2004
SPACA1 Sperm acrosome membrane-associated protein 1 81833 Q9HBV2 IP; LC-MS/MS
Huttlin EL , et al. 2015
SQLE squalene epoxidase 6713 Q14534 IP; LC-MS/MS
Huttlin EL , et al. 2015
SRPRB signal recognition particle receptor, B subunit 58477 Q549N5 IP; LC-MS/MS
Huttlin EL , et al. 2015
ST3GAL1 ST3 beta-galactoside alpha-2,3-sialyltransferase 1 6482 Q11201 IP; LC-MS/MS
Huttlin EL , et al. 2015
STEAP3 STEAP family member 3, metalloreductase 55240 Q658P3 IP; LC-MS/MS
Huttlin EL , et al. 2015
TIMM23 translocase of inner mitochondrial membrane 23 homolog (yeast) 100287932 O14925 IP; LC-MS/MS
Huttlin EL , et al. 2015
TMEM168 transmembrane protein 168 64418 Q9H0V1 IP; LC-MS/MS
Huttlin EL , et al. 2015
TMEM5 Transmembrane protein 5 10329 Q9Y2B1 IP; LC-MS/MS
Huttlin EL , et al. 2015
TMEM63A CSC1-like protein 1 9725 O94886 IP; LC-MS/MS
Huttlin EL , et al. 2015
TMEM63B transmembrane protein 63B 55362 Q5T3F8 IP; LC-MS/MS
Huttlin EL , et al. 2015
TNPO3 transportin 3 23534 B3KMX1 IP; LC-MS/MS
Huttlin EL , et al. 2015
TOR1A torsin family 1, member A (torsin A) 1861 O14656 IP; LC-MS/MS
Huttlin EL , et al. 2015
TRABD TraB domain containing 80305 Q9H4I3 IP; LC-MS/MS
Huttlin EL , et al. 2015
UBC ubiquitin C 7316 P63279 Affinity Capture-MS
Emanuele MJ , et al. 2011
UXS1 UDP-glucuronate decarboxylase 1 80146 Q8NBZ7 IP; LC-MS/MS
Huttlin EL , et al. 2015
VAC14 Vac14 homolog (S. cerevisiae) 55697 Q08AM6 IP; LC-MS/MS
Huttlin EL , et al. 2015
VSIG4 V-set and immunoglobulin domain-containing protein 4 11326 Q9Y279 IP; LC-MS/MS
Huttlin EL , et al. 2015
Auts2 autism susceptibility candidate 2 319974 Q6PED7 ChIP-Seq
Oksenberg N , et al. 2014
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
GRIN1 glutamate receptor, ionotropic, NMDA1 (zeta 1) 14810 P35438 IP; LC-MS/MS
Frank RA , et al. 2016
Mir137 microRNA 137 387155 N/A Luciferase reporter assay
Hwang HW , et al. 2016
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
Ania-3/Homer homer homolog 1 (Drosophila) 29546 Q9Z214 IP/WB
Sgambato-Faure V , et al. 2006
CHRNA7 cholinergic receptor, nicotinic, alpha 7 (neuronal) 25302 Q05941 in silico target prediction; IP/WB
Gmez-Varela D , et al. 2012
GRIN1 glutamate receptor, ionotropic, N-methyl D-aspartate 1 24408 P35439 IP/WB; GST
Garside ML , et al. 2009
GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A 24409 Q00959 IP/WB; GST
Garside ML , et al. 2009
STX1A syntaxin 1A (brain) 116470 P32851 IP/WB; GST
Garside ML , et al. 2009

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