Deciphering deleterious missense variants in the MC4R gene in the pathogenesis of obesity

4区医学 Q3 Nursing

Endocrinologia, Diabetes y Nutricion Pub Date : 2025-02-25 DOI:10.1016/j.endinu.2025.501559

Meriem El Fessikh , Hanaa Skhoun , Zohra Ouzzif , Jamila El Baghdadi

{"title":"Deciphering deleterious missense variants in the MC4R gene in the pathogenesis of obesity","authors":"Meriem El Fessikh , Hanaa Skhoun , Zohra Ouzzif , Jamila El Baghdadi","doi":"10.1016/j.endinu.2025.501559","DOIUrl":null,"url":null,"abstract":"<div><div>The <em>MC4R</em> gene plays a critical role in regulating food intake, making it an important model for studying genetic mutations that impact the protein function. This study aimed to identify the most deleterious functional and structural variants in individuals with obesity by analyzing SNPs from the NCBI dbSNP database and selecting pathogenic variants from ClinVar. Bioinformatics tools were employed to predict deleterious SNPs, and conservation analysis was performed using ConSurf. Stability predictions were made with MUpro, I-Mutant2.0, and iStable. The 3D structure of the MC4R protein was examined using YASARA view. A total of 20 out of 348 missense mutations were associated with obesity. Fifteen of these variants were predicted to be the most deleterious. Eight variants located in conserved regions were found to significantly reduce protein stability and cause structural changes (S58C, E61K, N62S, I69R, D90N, R165Q, P299H, and I316S), indicating their potential as obesity biomarkers and therapeutic targets.</div></div>","PeriodicalId":37725,"journal":{"name":"Endocrinologia, Diabetes y Nutricion","volume":"72 4","pages":"Article 501559"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrinologia, Diabetes y Nutricion","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2530016425000205","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Nursing","Score":null,"Total":0}

引用次数: 0

Abstract

The MC4R gene plays a critical role in regulating food intake, making it an important model for studying genetic mutations that impact the protein function. This study aimed to identify the most deleterious functional and structural variants in individuals with obesity by analyzing SNPs from the NCBI dbSNP database and selecting pathogenic variants from ClinVar. Bioinformatics tools were employed to predict deleterious SNPs, and conservation analysis was performed using ConSurf. Stability predictions were made with MUpro, I-Mutant2.0, and iStable. The 3D structure of the MC4R protein was examined using YASARA view. A total of 20 out of 348 missense mutations were associated with obesity. Fifteen of these variants were predicted to be the most deleterious. Eight variants located in conserved regions were found to significantly reduce protein stability and cause structural changes (S58C, E61K, N62S, I69R, D90N, R165Q, P299H, and I316S), indicating their potential as obesity biomarkers and therapeutic targets.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Endocrinologia, Diabetes y Nutricion Nursing-Nutrition and Dietetics

CiteScore

2.10

自引率

0.00%

发文量

169

审稿时长

35 days

期刊介绍： Endocrinología, Diabetes y Nutrición is the official journal of the Spanish Society of Endocrinology and Nutrition (Sociedad Española de Endocrinología y Nutrición, SEEN) and the Spanish Society of Diabetes (Sociedad Española de Diabetes, SED), and was founded in 1954. The aim of the journal is to improve knowledge and be a useful tool in practice for clinical and laboratory specialists, trainee physicians, researchers, and nurses interested in endocrinology, diabetes, nutrition and related disciplines. It is an international journal published in Spanish (print and online) and English (online), covering different fields of endocrinology and metabolism, including diabetes, obesity, and nutrition disorders, as well as the most relevant research produced mainly in Spanish language territories. The quality of the contents is ensured by a prestigious national and international board, and by a selected panel of specialists involved in a rigorous peer review. The result is that only manuscripts containing high quality research and with utmost interest for clinicians and professionals related in the field are published. The Journal publishes Original clinical and research articles, Reviews, Special articles, Clinical Guidelines, Position Statements from both societies and Letters to the editor. Endocrinología, Diabetes y Nutrición can be found at Science Citation Index Expanded, Medline/PubMed and SCOPUS.