PUBLICATION
NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy
- Authors
- McTiernan, N., Gill, H., Prada, C.E., Pachajoa, H., Lores, J., CAUSES study, Arnesen, T.
- ID
- ZDB-PUB-220119-12
- Date
- 2021
- Source
- European journal of human genetics : EJHG 29: 280-288 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Acetylation
- Amino Acid Sequence
- Animals
- Child, Preschool
- Female
- Genetic Predisposition to Disease/genetics*
- HeLa Cells
- Humans
- Intellectual Disability/genetics
- Mice
- Models, Molecular
- Mutation
- N-Terminal Acetyltransferase A/chemistry
- N-Terminal Acetyltransferase A/genetics*
- N-Terminal Acetyltransferase E/chemistry
- N-Terminal Acetyltransferase E/genetics*
- Phenotype
- Protein Conformation
- Proteus Syndrome/diagnostic imaging
- Proteus Syndrome/genetics*
- Rats
- Sequence Alignment
- Yeasts
- Zebrafish
- PubMed
- 32973342 Full text @ Eur. J. Hum. Genet.
Citation
McTiernan, N., Gill, H., Prada, C.E., Pachajoa, H., Lores, J., CAUSES study, Arnesen, T. (2021) NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy. European journal of human genetics : EJHG. 29:280-288.
Abstract
Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping