Human Gene Module / Chromosome 4 / NAA15

NAA15N(alpha)-acetyltransferase 15, NatA auxiliary subunit 

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
21 / 0
Aliases
NAA15, Ga19,  NARG1,  NAT1P,  NATH,  TBDN,  TBDN100
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
4q31.1
Associated Disorders
-
Relevance to Autism

This gene was identified in an ASD whole-exome sequencing study and subsequent TADA (transmission and de novo association) analysis as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (De Rubeis et al., 2014).

Molecular Function

Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity. The NAT activity may be important for vascular, hematopoietic and neuronal growth and development.

Reports related to NAA15 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
2 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No -
3 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
4 Recent recommendation Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
5 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
Rare Variants   (21)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.309C>G p.Tyr103Ter stop_gained De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1014G>T p.Lys338Asn missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1319T>C p.Leu440Ser missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
del(AC) - frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1018T>C p.Ser340Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1763G>A p.Arg588His missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
CAAAGAAA/CAAA - frameshift_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.154A>T p.Lys52Ter stop_gained Unknown - Multi-generational 28191889 Stessman HA , et al. (2017)
c.239_240del p.His80ArgfsTer17 frameshift_variant Unknown - - 28191889 Stessman HA , et al. (2017)
c.532_533del p.Gln178ThrfsTer5 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.868G>T p.Gly290Ter stop_gained Unknown - - 28191889 Stessman HA , et al. (2017)
c.1348A>G p.Lys450Glu missense_variant Familial Paternal - 28191889 Stessman HA , et al. (2017)
c.1424C>T p.Ala475Val missense_variant Unknown - - 28191889 Stessman HA , et al. (2017)
c.1695T>A p.Tyr565Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.1988del p.Pro663ArgfsTer2 frameshift_variant Unknown - - 28191889 Stessman HA , et al. (2017)
c.2086A>T p.Lys696Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.2344C>T p.Arg782Ter stop_gained Unknown - - 28191889 Stessman HA , et al. (2017)
c.225_230delTGACTTinsT p.Asp76GlufsTer20 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.334G>A p.Asp112Asn missense_variant Unknown - - 28191889 Stessman HA , et al. (2017)
c.2389A>T p.Arg797Ter stop_gained Unknown - - 28191889 Stessman HA , et al. (2017)
c.529_530del p.Thr177fs frameshift_variant De novo - Multiplex 28263302 C Yuen RK , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

A de novo LoF variant and a de novo missense variant that is predicted to be damaging were identified in the NAA15 gene in unrelated ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified NAA15 as a gene meeting high statistical significance with a 0.05< FDR ?0.1, meaning that this gene had a ?90% chance of being a true autism gene (PMID 25363760). Three novel de novo loss-of-function variants in NAA15 were identified in probands reported to have a formal diagnosis of ASD in the Supplementary Material from Stessman et al., 2017, bringing the total number of ASD-associated de novo LoF variants in NAA15 to four.

1

High Confidence

See all Category 1 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.

04-01-2017
1

Initial score established: 1

Description

A de novo LoF variant and a de novo missense variant that is predicted to be damaging were identified in the NAA15 gene in unrelated ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified NAA15 as a gene meeting high statistical significance with a 0.05< FDR ?0.1, meaning that this gene had a ?90% chance of being a true autism gene (PMID 25363760). Three novel de novo loss-of-function variants in NAA15 were identified in probands reported to have a formal diagnosis of ASD in the Supplementary Material from Stessman et al., 2017, bringing the total number of ASD-associated de novo LoF variants in NAA15 to four.

CNVs associated with NAA15(1 CNVs)
4q31.1 6 Deletion-Duplication 10  /  18
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
C15ORF63 Huntingtin-interacting protein K Human Protein Binding 25764 Q9NX55
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