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Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 6-7% of people worldwide (Wilcutt, 2012). MAOA is a gene that encodes monoamine oxidase A, an enzyme responsible for the regulation and metabolism of monoamines thought to be associated with ADHD. This study investigates a leucine to serine swap at amino acid position 32 in FAD-binding domain of the enzyme monoamine oxidase A. Results from in silico prediction tools and molecular dynamics modeling provide evidence to support pathogenicity of the L32S missense variant of monoamine oxidase A.
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This content will become publicly available on January 1, 2026
The disruptive influence of the Ala218Val variant on the ENG protein
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease that interferes with the formation of arteries. The ENG gene encodes for the protein endoglin which is used to properly develop and remodel arteries. The removal of endoglin forms telangiectasias that cause bleeding from the nose and vital organs. This study investigates the impact of one of the many variants of uncertain significance of ENG associated with HHT. The missense swap of alanine for valine at position 218 (Ala218Val) was characterized through computational metrics from in silico pathogenicity prediction tools, conservation analysis, and molecular dynamics simulation (MDS). The structural residue is highly conserved over multiple species and buried. The missense swap resulted in a difference in movement from the wild type according to MDS in a simulated aqueous environment. Therefore, it is predicted to be likely pathogenic.
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- Award ID(s):
- 2120918
- PAR ID:
- 10614660
- Publisher / Repository:
- microPublication Biology
- Date Published:
- Journal Name:
- microPublication Biology
- Volume:
- 2025
- ISSN:
- 2578-9430
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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