A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio.
10.3760/cma.j.cn511374-20210120-00060
- VernacularTitle:一个孤独症谱系障碍核心家系
KIF1A基因错义变异及其蛋白表达和结构分析
- Author:
Yan HUANG
1
;
Jian JIAO
;
Manxue ZHANG
;
Mingjing SITU
;
Danfeng YUAN
;
Peng LYU
;
Sixun LI
;
Zhuo WANG
;
Yanping YANG
;
Yi HUANG
Author Information
1. Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China. huangyu@scu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Autism Spectrum Disorder/genetics*;
Child;
Female;
Humans;
Kinesin/genetics*;
Mutation;
Mutation, Missense;
Pregnancy;
Protein Domains;
Whole Exome Sequencing
- From:
Chinese Journal of Medical Genetics
2021;38(7):620-625
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene.
METHODS:The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant.
RESULTS:The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function.
CONCLUSION:The KIF1A gene may be a risk gene for ASD.
