Human Gene Module / Chromosome 19 / ABCA7

ABCA7ATP-binding cassette, sub-family A (ABC1), member 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
20 / 0
Aliases
ABCA7, ABCA-SSN,  ABCX
Associated Syndromes
-
Chromosome Band
19p13.3
Associated Disorders
-
Relevance to Autism

ABCA7 showed the strongest evidence of being associated with autism (OR=8.5 0.75) with all rare variant transmission disequilibrium test (RV-TDT) methods (range of p-values, 1.4E-04 to 2.9E-04) that were used to analyze exome data from 199 autism trios from the Simons Simplex Collection (He et al., 2014).

Molecular Function

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. It plays a role in phagocytosis by macrophages of apoptotic cells and may function in apolipoprotein-mediated phospholipid efflux from cells, mediate cholesterol efflux, and regulate cellular ceramide homeostasis during keratinocytes differentiation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ABCA7 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Rare-variant extensions of the transmission disequilibrium test: application to autism exome sequence data He Z , et al. (2013) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (20)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1722G>T p.Glu574Asp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.216T>G p.Gly72%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.5288T>A p.Val1763Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.995G>A p.Gly332Glu missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.1324G>A p.Gly442Arg missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.1534C>G p.Arg512Gly missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.2629G>A p.Ala877Thr missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.2858C>A p.Ala953Asp missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.4795G>A p.Val1599Met missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.5344C>T p.Arg1782Trp missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.5435G>A p.Arg1812His missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.5648C>T p.Thr1883Met missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.6322G>A p.Glu2108Lys missense_variant Familial - Simplex 24360806 He Z , et al. (2013)
c.3423G>A p.Glu1141= stop_gained Familial Paternal Simplex 31674007 Wu H , et al. (2019)
c.1637T>G p.Leu546Arg missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.5783G>A p.Gly1928Glu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1445+1G>C - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.3229C>T p.Gln1077Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.3352C>T p.Arg1118Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.2478dup p.Leu827AlafsTer68 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

ABCA7 showed the strongest evidence of being associated with autism (OR = 8.5 0.75) with all rare variant transmission disequilibrium test (RV-TDT) methods (range of p-values, 1.4E-04 to 2.9E-04) that were used to analyze exome data from 199 autism trios from the Simons Simplex Collection (He et al., 2014). A de novo missense variant that was predicted to be damaging was identifed in ABCA7 in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

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

ABCA7 showed the strongest evidence of being associated with autism (OR = 8.5 0.75) with all rare variant transmission disequilibrium test (RV-TDT) methods (range of p-values, 1.4E-04 to 2.9E-04) that were used to analyze exome data from 199 autism trios from the Simons Simplex Collection (He et al., 2014). A de novo missense variant that was predicted to be damaging was identifed in ABCA7 in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

ABCA7 showed the strongest evidence of being associated with autism (OR = 8.5 0.75) with all rare variant transmission disequilibrium test (RV-TDT) methods (range of p-values, 1.4E-04 to 2.9E-04) that were used to analyze exome data from 199 autism trios from the Simons Simplex Collection (He et al., 2014). A de novo missense variant that was predicted to be damaging was identifed in ABCA7 in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

ABCA7 showed the strongest evidence of being associated with autism (OR = 8.5 0.75) with all rare variant transmission disequilibrium test (RV-TDT) methods (range of p-values, 1.4E-04 to 2.9E-04) that were used to analyze exome data from 199 autism trios from the Simons Simplex Collection (He et al., 2014). A de novo missense variant that was predicted to be damaging was identifed in ABCA7 in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

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

Increased from to 4

Description

ABCA7 showed the strongest evidence of being associated with autism (OR = 8.5 ± 0.75) with all rare variant transmission disequilibrium test (RV-TDT) methods (range of p-values, 1.4E-04 to 2.9E-04) that were used to analyze exome data from 199 autism trios from the Simons Simplex Collection (He et al., 2014). A de novo missense variant that was predicted to be damaging was identifed in ABCA7 in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

Krishnan Probability Score

Score 0.41066250045188

Ranking 22611/25841 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 1.8916039899045E-36

Ranking 18192/18225 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 0.94894715856756

Ranking 17891/18665 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 12

Ranking 153/461 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 -0.3521711725604

Ranking 17843/20870 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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