Human Gene Module / Chromosome 7 / ABCA13

ABCA13ATP binding cassette subfamily A member 13

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 11
Rare Variants / Common Variants
30 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
7p12.3
Associated Disorders
-
Relevance to Autism

De novo missense variants in the ABCA13 gene have been identified in ASD probands in whole-exome sequencing studies (Neale et al., 2012; Iossifov et al., 2012; De Rubeis et al., 2014). A heterozygous deletion disrupting the ABCA13 gene was identified in a Japanese macaque that spontaneously displayed autistic traits such as impaired social ability and restricted and repetitive behaviors; no CNVs affecting ABCA13 were observed in a control group of 335 Japanese macaques (Yoshida et al., 2016). Pan-neuron-specific knockdown of a gene in Drosophila that shows high homology to human ABCA genes, including ABCA13, resulted in impaired social interactions and early onset of evening activity in adult flies, as well as an increase in satellite boutons in presynaptic terminals of motor neurons in third instar larvae (Ueoka et al., 2017).

Molecular Function

In human, the ATP-binding cassette (ABC) family of transmembrane transporters has at least 48 genes and 7 gene subfamilies. This gene is a member of ABC gene subfamily A (ABCA). Genes within the ABCA family typically encode several thousand amino acids. Like other ABC transmembrane transporter proteins, this protein has 12 or more transmembrane alpha-helix domains that likely arrange to form a single central chamber with multiple substrate binding sites. It is also predicted to have two large extracellular domains and two nucleotide binding domains as is typical for ABCA proteins.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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Fruit fly
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ABCA13 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Patterns and rates of exonic de novo mutations in autism spectrum disorders Neale BM , et al. (2012) Yes -
2 Support De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Support Single-neuron and genetic correlates of autistic behavior in macaque Yoshida K , et al. (2016) No -
5 Recent Recommendation Novel Drosophila model for psychiatric disorders including autism spectrum disorder by targeting of ATP-binding cassette protein A Ueoka I , et al. (2017) No -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Recent Recommendation - Kimura H et al. (2022) Yes ADHD
9 Support - Krgovic D et al. (2022) Yes ADHD, OCD
10 Support - Zhou X et al. (2022) Yes -
11 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (30)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1180G>T p.Glu394Ter stop_gained Unknown - - 35811316 Kimura H et al. (2022)
c.10688+1G>C - splice_site_variant Unknown - - 35811316 Kimura H et al. (2022)
c.5373C>T p.Phe1791%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.6483A>G p.Leu2161%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.9075C>T p.Cys3025%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.424C>T p.Arg142Ter stop_gained Familial Maternal - 35811316 Kimura H et al. (2022)
c.10277A>G p.Asn3426Ser missense_variant De novo - - 22495311 Neale BM , et al. (2012)
c.1663C>T p.Arg555Cys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.8264G>A p.Trp2755Ter stop_gained Familial Paternal - 35811316 Kimura H et al. (2022)
c.7982A>G p.Asn2661Ser missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.3328G>A p.Val1110Ile missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.13619C>G p.Ala4540Gly missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.455C>T p.Ser152Phe missense_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
c.586G>A p.Glu196Lys missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.8953dup p.Gln2985ProfsTer4 frameshift_variant Unknown - - 35813072 Krgovic D et al. (2022)
c.7735del p.Ile2579Ter frameshift_variant Familial Paternal - 35811316 Kimura H et al. (2022)
c.12032G>A p.Arg4011Gln missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.12525G>C p.Glu4175Asp missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.424C>T p.Arg142Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.895G>T p.Glu299Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.70-1G>T - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.424C>T p.Arg142Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.8726+1G>A - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.10205-2A>G - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.10803+1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.4013C>A p.Ser1338Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.8850G>A p.Trp2950Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.8850G>A p.Trp2950Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.14416C>T p.Gln4806Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.5202del p.Pro1736LeufsTer8 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo missense variants in the ABCA13 gene have been identified in ASD probands in whole-exome sequencing studies (Neale et al., 2012; Iossifov et al., 2012; De Rubeis et al., 2014). A heterozygous deletion disrupting the ABCA13 gene was identified in a Japanese macaque that spontaneously displayed autistic traits such as impaired social ability and restricted and repetitive behaviors; no CNVs affecting ABCA13 were observed in a control group of 335 Japanese macaques (Yoshida et al., 2016). Pan-neuron-specific knockdown of a gene in Drosophila that shows high homology to human ABCA genes, including ABCA13, resulted in impaired social interactions and early onset of evening activity in adult flies, as well as an increase in satellite boutons in presynaptic terminals of motor neurons in third instar larvae (Ueoka et al., 2017).

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

De novo missense variants in the ABCA13 gene have been identified in ASD probands in whole-exome sequencing studies (Neale et al., 2012; Iossifov et al., 2012; De Rubeis et al., 2014). A heterozygous deletion disrupting the ABCA13 gene was identified in a Japanese macaque that spontaneously displayed autistic traits such as impaired social ability and restricted and repetitive behaviors; no CNVs affecting ABCA13 were observed in a control group of 335 Japanese macaques (Yoshida et al., 2016). Pan-neuron-specific knockdown of a gene in Drosophila that shows high homology to human ABCA genes, including ABCA13, resulted in impaired social interactions and early onset of evening activity in adult flies, as well as an increase in satellite boutons in presynaptic terminals of motor neurons in third instar larvae (Ueoka et al., 2017).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

De novo missense variants in the ABCA13 gene have been identified in ASD probands in whole-exome sequencing studies (Neale et al., 2012; Iossifov et al., 2012; De Rubeis et al., 2014). A heterozygous deletion disrupting the ABCA13 gene was identified in a Japanese macaque that spontaneously displayed autistic traits such as impaired social ability and restricted and repetitive behaviors; no CNVs affecting ABCA13 were observed in a control group of 335 Japanese macaques (Yoshida et al., 2016). Pan-neuron-specific knockdown of a gene in Drosophila that shows high homology to human ABCA genes, including ABCA13, resulted in impaired social interactions and early onset of evening activity in adult flies, as well as an increase in satellite boutons in presynaptic terminals of motor neurons in third instar larvae (Ueoka et al., 2017).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

De novo missense variants in the ABCA13 gene have been identified in ASD probands in whole-exome sequencing studies (Neale et al., 2012; Iossifov et al., 2012; De Rubeis et al., 2014). A heterozygous deletion disrupting the ABCA13 gene was identified in a Japanese macaque that spontaneously displayed autistic traits such as impaired social ability and restricted and repetitive behaviors; no CNVs affecting ABCA13 were observed in a control group of 335 Japanese macaques (Yoshida et al., 2016). Pan-neuron-specific knockdown of a gene in Drosophila that shows high homology to human ABCA genes, including ABCA13, resulted in impaired social interactions and early onset of evening activity in adult flies, as well as an increase in satellite boutons in presynaptic terminals of motor neurons in third instar larvae (Ueoka et al., 2017).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2017
icon
4

Increased from to 4

Description

De novo missense variants in the ABCA13 gene have been identified in ASD probands in whole-exome sequencing studies (Neale et al., 2012; Iossifov et al., 2012; De Rubeis et al., 2014). A heterozygous deletion disrupting the ABCA13 gene was identified in a Japanese macaque that spontaneously displayed autistic traits such as impaired social ability and restricted and repetitive behaviors; no CNVs affecting ABCA13 were observed in a control group of 335 Japanese macaques (Yoshida et al., 2016). Pan-neuron-specific knockdown of a gene in Drosophila that shows high homology to human ABCA genes, including ABCA13, resulted in impaired social interactions and early onset of evening activity in adult flies, as well as an increase in satellite boutons in presynaptic terminals of motor neurons in third instar larvae (Ueoka et al., 2017).

Krishnan Probability Score

Score 0.46023024844183

Ranking 9484/25841 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 3.3073276525505E-78

Ranking 18224/18225 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 0.94475283035332

Ranking 16199/18665 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
Zhang D Score

Score -0.14385516331978

Ranking 13950/20870 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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