NAA10-related genetic disorders are caused by changes in the NAA10 gene. The NAA10 gene is located on the X chromosome and is thought to be important in the development and function of the brain and other organs. N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively.
Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants. All mutations identified to date with NAA10-syndrome appear to either change single amino acids in the protein, alter the splicing of the messenger RNA, or introduce a frameshift mutation at the C-terminal end of the protein. This is a very rare condition, with only several dozen families identified worldwide. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome, in which a splice variant reduced the amount of full length protein by >95%, in the presence of a small amount of truncated protein. However, none of the children with missense variants have microphthalmia, so there is clearly a difference in function between missense variants and these latter truncating or splice-site variants.