Human Gene Module / Chromosome 15 / ATP10A

ATP10AProbable phospholipid-transporting ATPase VA

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
8 / 10
Rare Variants / Common Variants
7 / 5
Aliases
ATP10A, ATP10C
Associated Syndromes
-
Chromosome Band
15q12
Associated Disorders
-
Relevance to Autism

Conflicting studies have shown positive genetic association and no genetic association of the ATP10C gene with autism.

Molecular Function

The encoded protein is a member of the aminophospholipid-transporting ATPase family.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ATP10A (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome Meguro M , et al. (2001) No -
2 Negative Association Mutation screening and transmission disequilibrium study of ATP10C in autism Kim SJ , et al. (2002) Yes -
3 Primary Dense linkage disequilibrium mapping in the 15q11-q13 maternal expression domain yields evidence for association in autism Nurmi EL , et al. (2003) Yes -
4 Recent Recommendation A type IV P-type ATPase affects insulin-mediated glucose uptake in adipose tissue and skeletal muscle in mice Dhar MS , et al. (2006) No -
5 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
6 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
7 Support Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms D'Gama AM , et al. (2015) Yes -
8 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
9 Support Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort da Silva Montenegro EM , et al. (2019) Yes -
10 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1319G>A p.Arg440Gln missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.3797A>G p.Gln1266Arg missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.622C>T p.Arg208Trp missense_variant Unknown - Unknown 26637798 D'Gama AM , et al. (2015)
c.1560C>A p.His520Gln stop_gained Familial Maternal Simplex 30504930 Guo H , et al. (2018)
c.4156G>A p.Glu1386Lys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.497G>A p.Gly166Glu missense_variant De novo - Simplex 31696658 da Silva Montenegro EM , et al. (2019)
c.4276del p.Leu1426CysfsTer66 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.449+31878A>G - intron_variant - - - 12851639 Nurmi EL , et al. (2003)
c.450-31252C>A - intron_variant - - - 12851639 Nurmi EL , et al. (2003)
c.-417A>G - 2KB_upstream_variant - - - 12851639 Nurmi EL , et al. (2003)
c.-770T>C - 2KB_upstream_variant - - - 12851639 Nurmi EL , et al. (2003)
c.4449A>G;c.2880A>G p.(=) synonymous_variant - - - 12851639 Nurmi EL , et al. (2003)
SFARI Gene score
2

Strong Candidate

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

Reports Added
[Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort.2019] [New Scoring Scheme]
10/1/2018
3
icon
3

Decreased from 3 to 3

Description

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

Reports Added
[Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

Reports Added
[Mutation screening and transmission disequilibrium study of ATP10C in autism.2002] [Dense linkage disequilibrium mapping in the 15q11-q13 maternal expression domain yields evidence for association in autism.2003] [A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome.2001] [A type IV P-type ATPase affects insulin-mediated glucose uptake in adipose tissue and skeletal muscle in mice.2006] [Excess of rare, inherited truncating mutations in autism.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015]
4/1/2015
3
icon
3

Decreased from 3 to 3

Description

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

Reports Added
[Excess of rare, inherited truncating mutations in autism.2015]
7/1/2014
No data
icon
3

Increased from No data to 3

Description

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

4/1/2014
No data
icon
3

Increased from No data to 3

Description

Candidate gene based on being in 15q11-13 duplication region. Linkage (Freitag, 2007) and association studies have inconsistent findings in this autism candidate region. Nurmi et al., (2001) found the marker D15S122, located at the 5? end of the gene UBE3A, associated with autism in the Collaborative Linkage Study of Autism (CLSA); however, Cook et al., (1998) could not find any association between the same locus and autism. Subsequently, Nurmi et al., (2003a) failed to replicate the initial finding in a larger sample, while they described the preferential transmission of single-nucleotide polymorphisms (SNPs) rs1047700 and rs1345098 and a three-SNPs haplotype in ATP10A. The significant association of ATP10A (Nurmi et al., 2003a), however, was not observed in a previous report by Kim et al., (2002). Recently, Kato et al., (2008) found a four-marker haplotype in ATP10A significantly associated with autism in Japanese population.

Krishnan Probability Score

Score 0.49456656957478

Ranking 3577/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.61101349923777

Ranking 4945/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.9474363835552

Ranking 17275/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 5

Ranking 273/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.16667443507289

Ranking 4861/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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