Relevance to Autism

A de novo loss-of-function (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 in De Rubeis et al., 2014 (PMID 25363760). Furthermore, analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report 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. Three novel de novo LoF variants in NAA15 were identified in probands reported to have a formal diagnosis of ASD in the Supplementary Material from Stessman et al., 2017 (PMID 28191889). An additional de novo LoF variant in NAA15 was identified in an ASD proband from a multiplex family by whole genome sequencing as part of the MSSNG initiative in Yuen et al., 2017 (PMID 28263302). Phenotypic characterization of 38 individuals from 33 unrelated families with de novo or inherited loss-of-function variants in NAA15, many of whom were previously unreported, identified recurrent phenotypes, including intellectual disability (23/23 cases, 100%), speech delay (32/33 cases, 97%), motor delay and related abnormalities (31/32 cases, 97%), ASD, ADHD, or behavioral issues (30/33 cases, 91%), and mild dysmorphic features (18/28 cases, 64%). Two additional de novo loss-of-function variants in the NAA15 gene were reported in ASD probands from the SPARK cohort in Zhou et al., 2022; a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified NAA15 as a gene reaching exome-wide significance (P < 2.5E-06).

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.

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References

Model Summary

NAT1-VDRC110689 mutants showed abnormal patterns of wing position, impaired locomotor activity, as well as increased adult early lethality. NAT1-VDRC17571 mutants' initial jump response was impaired.

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