Human Gene最新文献

{"title":"Identification of overlapping molecular mechanisms in tuberculosis and sarcoidosis: A bioinformatics approach","authors":"Sanjukta Dasgupta,&nbsp;Sayantan Ghosh","doi":"10.1016/j.humgen.2024.201329","DOIUrl":"10.1016/j.humgen.2024.201329","url":null,"abstract":"<div><h3>Background</h3><p>Tuberculosis (TB) and sarcoidosis are chronic granulomatous diseases sharing similar symptoms, immune responses, and radiological characteristics. Transcriptome analysis offers insights into gene expression, regulation, and cellular processes, facilitating the understanding of shared molecular mechanisms.</p></div><div><h3>Methods</h3><p>Microarray datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) were analysed to identify differentially expressed genes (DEGs) in TB and sarcoidosis compared to controls. DEGs were identified using the GEO2R tool, and subsequent functional enrichment analysis was conducted using EnrichR. Protein-protein interaction (PPI) networks, as well as gene-miRNA and transcription factor-DEG interaction networks, were constructed. In addition, pathway analysis and molecular docking of target proteins were conducted to further elucidate the biological mechanisms involved in both diseases.</p></div><div><h3>Results</h3><p>Fifteen genes, including <em>ANKRD22, BATF2, DHRS9, EPSTI1, ETV7, FCGR1A, FCGR1B, GBP1, GBP5, SERPING1, NELL2, CCR7, PASK, LRRN3</em>, and <em>SLC16A10</em>, were commonly altered in TB and sarcoidosis as compared to controls. Gene network analysis revealed 48.89% co-expression and 26.10% physical interaction between these overlapping genes. PPI networks showed a total of 15 nodes and 28 edges present between the connected proteins (PPI enrichment <em>p</em>-value:&lt;1.0e−16). MiRNAs and transcription factors that exhibited the highest interaction with DEGs included hsa-miR-26a-5p, hsa-miR-16-5p, hsa-miR-335-5p, and EPAS1, HIF1A, KLF2, respectively. Pathway analysis indicated enrichment of IFN gamma signaling in both diseases. Molecular docking revealed weighted scores of −884.4, −851.9, and − 637.1 between three key proteins (PASK-GBP1, PASK-GBP5, and GBP1-GBP5).</p></div><div><h3>Conclusion</h3><p>The shared dysregulated genes in TB and sarcoidosis demonstrate notable co-expression and physical interaction, constituting a PPI network enriched in the IFN-gamma signaling pathway.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201329"},"PeriodicalIF":0.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling key genes in esophageal and lung adenocarcinoma progression: A combined high-throughput analysis and molecular docking approach for targeted therapies","authors":"Monira Binte Momin ,&nbsp;Md. Anwar Hossain ,&nbsp;Jannatul Ferdoush ,&nbsp;Alexander Wayne Garrott ,&nbsp;Sumaiya Afroz ,&nbsp;Tanjina Rahman ,&nbsp;Shipan Das Gupta","doi":"10.1016/j.humgen.2024.201327","DOIUrl":"10.1016/j.humgen.2024.201327","url":null,"abstract":"<div><h3>Background</h3><p>Esophageal carcinoma (ESCA) and Lung adenocarcinoma (LUAD) are the prominent causes of death worldwide. There is an urgent need to identify and characterize potential biomarkers for these malignancies to enhance early cancer prognosis. Integrating computational-based early cancer detection with wet lab-based research offers a promising approach toward early-stage cancer prognosis.</p></div><div><h3>Methodology</h3><p>Two ESCA datasets (GSE17351, GSE23400) with 58 cancerous and 58 normal samples, along with two LUAD datasets (GSE18842, GSE74706) totaling 64 cancer samples and 63 controls, were used to identify DEGs. Visualization of DEGs was achieved using heat-maps, volcano plots, and Venn diagrams. Hub genes were predicted via PPI analysis and the cytoHubba plugin in Cytoscape. Potential hub gene expressions were evaluated with box plots, stage plots, and survival plots for prognostic assessment via GEPIA2. AutoDockVina wizard of PyRx was utilized for molecular docking to determine optimal binding interactions between proteins and hit compounds.</p></div><div><h3>Findings</h3><p>Sixty common DEGs were identified, focusing on significant pathways in ESCA and LUAD. The top ten hub genes (<em>KIF4A, HMMR, CENPF, CDK1, ASPM, CDKN3, KIF2C, TTK, UBE2C</em>, and <em>MELK</em>) were found to be linked to both cancers via PPI analysis. Notably, high expression of <em>CDK1</em> was significantly associated with ESCA and LUAD progression, as evidenced by box plots, stage plots, and survival analysis. Upregulated expression of the targeted genes (CDK1) promotes multi-variant cancer progression that is observed by analyzing and comparing of all findings. Molecular docking with CDK1 highlighted four top compounds: Tanshinone I, Withanolide, Artemether, and Epigallocatechin, suggesting their potential as drug candidates for ESCA and LUAD treatment.</p></div><div><h3>Conclusions</h3><p>In conclusion, our discoveries unveil potential biomarker candidates, offer insights into ESCA and LUAD treatment strategies, and outline directions for further investigation, enriching our understanding of the pathogenesis of ESCA and LUAD.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201327"},"PeriodicalIF":0.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142041211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and bioinformatics illuminates punicalagin's pharmacological mechanisms countering drug resistance in hepatocellular carcinoma","authors":"Gajalakshmi Ramarajyam ,&nbsp;Ramadurai Murugan ,&nbsp;Selvam Rajendiran","doi":"10.1016/j.humgen.2024.201328","DOIUrl":"10.1016/j.humgen.2024.201328","url":null,"abstract":"<div><p><em>Background:</em> Hepatocellular carcinoma (HCC) poses a formidable global health challenge, exhibiting significant prevalence variations across diverse regions. This study delves into the potential therapeutic implications of punicalagin, a polyphenol abundant in pomegranates, for HCC. The primary objectives encompass the identification of potent molecular targets and enriched pathways influenced by punicalagin using integrated bioinformatic analysis. <em>Materials and methods:</em> Employing Gene Set Enrichment Analysis (GSEA), the study discerned potential differentially expressed genes (DEGs) in liver cancer. Collating information from diverse databases, including GEO2R, CTD database, and Gene Cards, revealed a set of 20 potential targets. A pharmacological network analysis was subsequently conducted using STITCH, with Cytoscape software pinpointing five highly upregulated genes within the punicalagin network such as SRC, CASP3, AKT1, IL6, and NOS3 via the cytohubba plugin. Furthermore, Gene Ontology (GO) analysis was employed to predict functional categories, unveiling key insights into the potential biological impact of punicalagin.</p><p><em>Results:</em> KEGG pathway analysis demonstrated enrichment in crucial pathways such as AMPK signaling, HIF1a, and mTOR signaling, shedding light on the molecular mechanisms influenced by punicalagin. Diagnostic assessments were performed by analyzing mRNA expression levels and overall survival for the identified targets, utilizing datasets from UALCAN and GEPIA databases. Structural confirmation of punicalagin interactions with its targets was accomplished through molecular docking studies, revealing robust binding associations with biomolecules such as SRC, CASP3, AKT1, IL6, and NOS3. Experimental validation involved RT-PCR, showcasing reduced expression levels of target biomolecules such as SRC, CASP3, AKT1, IL6, and NOS3 in HepG2 cells treated with punicalagin. <em>Conclusion:</em> These findings underscore the potential of punicalagin as a promising therapeutic avenue for liver cancer treatment, presenting a comprehensive approach that integrates computational insights with experimental evidence.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201328"},"PeriodicalIF":0.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational analyses of mitochondrial ATP6 gene reveal a possible association with abnormal levels of lactic acid and ammonia in Bangladeshi children with autism spectrum disorder: A case-control study","authors":"Md. Mahbub Hasan ,&nbsp;Maisha Adiba ,&nbsp;Molie Rahman ,&nbsp;Hosneara Akter ,&nbsp;Mohammed Uddin ,&nbsp;Akio Ebihara ,&nbsp;A.H.M. Nurun Nabi ,&nbsp;Tahirah Yasmin","doi":"10.1016/j.humgen.2024.201325","DOIUrl":"10.1016/j.humgen.2024.201325","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is a multifactorial and highly heterogeneous neurodevelopmental disorder. Mitochondrial dysfunction, caused by the genetic variations in the electron transport chain (ETC) complexes and marked by higher lactic acid and ammonia levels, can play a crucial role in the development of autism. This study focused on identifying genetic variants in the mitochondrial <em>ATP6</em> gene of children with ASD and their association with autism disease outcome, disease severity, lactic acid and ammonia levels. Ninety children were recruited of which 53 were with autism and the remaining 37 were healthy controls. The <em>ATP6</em> gene was amplified by PCR, purified, and sequenced by Sanger sequencing. In total forty-two genetic variants were identified within the gene. Among them 8886G &gt; A and 8911 T &gt; C were found to be associated with higher lactic acid levels and 8748C &gt; T, 8886G &gt; A, and 8964C &gt; T were associated with higher ammonia levels after the adjustment with age, gender, and disease response. Additionally, all the synonymous variants were found to alter the relative synonymous codon usage (RSCU) values, potentially affecting the protein's structure and translation rate. Although there was no significant association between any ATP6 variants and disease outcomes, the variants associated with mitochondrial dysfunction as reflected by abnormal levels of lactic acid and ammonia may provide an improved understanding of the pathophysiology of ASD. Therefore they need to be explored further along with other components of the electron transport complex.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201325"},"PeriodicalIF":0.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INHBB variants as genetic determinants of breast density modulate breast cancer risk","authors":"Vahideh Taherian ,&nbsp;Asma Khorshid Shamshiri ,&nbsp;Fatemeh Vakili ,&nbsp;Fatemeh Homaei Shandiz ,&nbsp;Donya Farrokh ,&nbsp;Alireza Pasdar ,&nbsp;Fahimeh Afzaljavan","doi":"10.1016/j.humgen.2024.201326","DOIUrl":"10.1016/j.humgen.2024.201326","url":null,"abstract":"<div><h3>Background</h3><p>One of the most common cancers worldwide is breast cancer (BC), which is influenced by genetics and environmental factors such as mammographic density. Studies suggested <em>INHBB</em> genetic polymorphisms as potential risk factors for breast cancer/density. Therefore, this study was conducted to validate this correlation in a cohort of the Iranian population.</p></div><div><h3>Methods</h3><p>Five ml of peripheral blood was collected from 200 patients and 200 healthy women. Mammographic density was determined by mammograms. <em>rs11902591</em>, <em>rs4328642,</em> and <em>rs10183524</em> of the <em>INHBB</em> gene were genotyped using the ARMS-PCR method. Haplotype frequencies and statistical analysis were estimated using PHASE and SPSS 16.0 software, respectively.</p></div><div><h3>Results</h3><p>There was no association between <em>rs1192591</em> and breast density, whereas this polymorphism was associated with breast cancer risk [per allele <em>p</em> = 0.040; OR = 0.56, 95%CI (0.32–0.97)]. Conversely, the C/T genotype of <em>rs4328642</em> was significantly higher in individuals with dense breasts [<em>p</em> = 0.002; OR = 2.31, 95%CI (1.37–3.89)]. Furthermore, <em>rs10183524</em> was statistically associated with breast density [<em>p</em> = 0.009; OR = 0.55, 95%CI (0.35–0.86)] and cancer risk [<em>p</em> = 0.031; OR = 0.52, 95%CI (0.29–0.94)]. Also, certain haplotypes and diplotypes of these markers were associated with BC risk and/or breast density.</p></div><div><h3>Conclusion</h3><p>According to the findings, <em>INHBB</em> gene polymorphisms affect cancer risk and density of the breast, and the interaction between alleles in the form of haplotypes and diplotypes may modulate the amount of the risk conferred by these variants.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201326"},"PeriodicalIF":0.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective epidemiological investigation of human leukocyte antigen-B*57:01 in HIV-1-infected Moroccan subjects","authors":"Imane Belbacha ,&nbsp;Soumia Benchekroun ,&nbsp;Rajae Bensghir ,&nbsp;Kamal Filali Marhoum ,&nbsp;Elharti Elmir ,&nbsp;Khalid Sadki ,&nbsp;Hicham Oumzil","doi":"10.1016/j.humgen.2024.201324","DOIUrl":"10.1016/j.humgen.2024.201324","url":null,"abstract":"<div><h3>Background</h3><p>The occurrence of hypersensitivity reactions to abacavir, a significant adverse effect, affects approximately 5–8% of Caucasians. Multiple studies conducted in diverse populations have underscored the association between Human Leukocyte Antigen-B*57:01 and abacavir-hypersensitivity reactions. In late 2021, the Moroccan National AIDS Program issued new anti-retroviral therapy protocols for HIV management, including abacavir as an option for the first-line ART regimen. However, data regarding the HLA-B*57:01 prevalence of HIV in Morocco is scarce. This study aims to assess the prevalence of HLA-B*57:01 in both HIV-1-infected children and adults in Morocco.</p></div><div><h3>Methods</h3><p>From April to December 2022, we screened 292 HIV-1 infected patients, 70 children and 222 adults, for the HLA-B*57:01 allele using sequence-specific oligonucleotide probes reverse hybridization method. The flow cytometry was used to assess the TCD4 lymphocyte count. The virological status was evaluated using quantitative real-time PCR. Sanger sequencing is under process to confirm the results obtained.</p></div><div><h3>Results</h3><p>Of 292 HIV-1-infected patients, 12 (4.1%) had the HLA-B*57:01 allele (95% CI, 2.1–7.1). 5 of 70 (7.2%) and 7 of 222 (3.2%) of children and adults were respectively, HLA-B*57:01 positive. There was no statistical association between clinical characteristics (TCD4 cell count and VL) and HLA-B*57:01 allele carriage.</p></div><div><h3>Conclusion</h3><p>The prevalence of HLA-B*57:01 in Moroccan patients was 4.1%, comparable with that of other Middle Eastern populations, higher than that in South African populations but lower than that in Caucasians and Southwest Asians. Our findings indicate an urgent need for HLA-B*57:01 screening before abacavir to reduce the risk of hypersensitivity reactions.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201324"},"PeriodicalIF":0.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pitt Hopkins syndrome – TCF4 gene deletion causing severe psychomotor delay","authors":"A.R. Ajina Khan ,&nbsp;Betsy Baby ,&nbsp;S.L. Akhil,&nbsp;Soumya Sundaram,&nbsp;Karthika Ajit Valaparambil","doi":"10.1016/j.humgen.2024.201323","DOIUrl":"10.1016/j.humgen.2024.201323","url":null,"abstract":"<div><p>Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder due to haploinsufficiency of <em>TCF4</em> and is clinically characterized by developmental delay, intellectual disability (ID), autism spectrum disorders, typical facial gestalt, seizures, high myopia and hyperventilation-apneic spells. Approximately in three-fourth cases of PTHS, a <em>de novo</em> pathogenic variant in <em>TCF4</em> is identified. In other instances, deletion of the chromosome region 18q21.2 in which encompasses <em>TCF4</em> is responsible and only chromosomal microarray (CMA) can reveal the microdeletion. This report describes the case of a 10 year-old girl with PTHS phenotype caused by a chromosome 18q21.2q22.1 deletion that included the <em>TCF4</em> gene. The patient had severe developmental and cognitive delay, autistic spectrum disorder, motor difficulties, and behavioral issues, all of which are typical with PTHS. Understanding the phenotypic variation is critical for accurate diagnosis in this syndrome, since deletions in <em>TCF4</em> may be missed if exome sequencing is sought instead of chromosomal microarray analysis (CMA).</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"41 ","pages":"Article 201323"},"PeriodicalIF":0.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic polymorphism of glyoxalase I gene (A419C and C-7 T) and nephropathy risk in patients with type 2 diabetes mellitus among north Indian population: A case-control study","authors":"Maithilikarpagaselvi Nachimuthu ,&nbsp;Tanu Kanwar ,&nbsp;Mohini Rathore ,&nbsp;Karli Sreenivasulu ,&nbsp;Nitin Kumar Bajpai ,&nbsp;Mithu Banerjee","doi":"10.1016/j.humgen.2024.201322","DOIUrl":"10.1016/j.humgen.2024.201322","url":null,"abstract":"<div><h3>Background</h3><p>The global burden of Diabetic nephropathy is rising and eventually leads to chronic kidney disease. Methylglyoxal (MGO) is an antecedent to advanced glycation end products (AGEs), implicated in diabetes mellitus microvascular complications. Glyoxalase I (GLO1), is the primary enzyme responsible for metabolizing methylglyoxal (MG). Any genetic variants of GLO1 may have a significant impact on the development of diabetic microvascular complications.</p></div><div><h3>Objectives</h3><p>To determine the association of rs1049346 and rs4746 (rs2736654) of Glyoxalase I gene polymorphism in type 2 Diabetes patients (T2DM) with nephropathy risk.</p></div><div><h3>Materials and methods</h3><p>The case-control study included a hundred T2DM with nephropathy and a hundred healthy controls. The TaqMan single nucleotide polymorphism genotyping assays were performed using Real-Time PCR to assess the genotype frequencies. The circulating levels of GLO-1 activity, MGO, CML and CEL were estimated using Enzyme-linked immunosorbent assay (ELISA).</p></div><div><h3>Results and discussion</h3><p>We observed increased serum levels of MGO, AGEs and decreased GLO-1 activity in diabetic nephropathy when compared to control. The patients carrying the CC genotypes (CC) and allele frequency of GLO-1 (rs1049346) were associated with nephropathy risk in T2DM patients (<em>p</em> &lt; 0.024). We found no association of rs4746 with nephropathy risk in patients with T2DM. The patients with the CC + CT genotype showed lower GLO-1 activity and increased MGO levels when compared to homozygous wild-type. The CA haplotype significantly increased the risk of T2DM nephropathy.</p></div><div><h3>Conclusion</h3><p>Patients with T2DM who carry the variant CC genotype of rs1049346 (A &gt; C) are at increased risk for developing nephropathy. The patients carrying the CC + CT genotype was associated with lower GLO-1 activity and increased MGO levels.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"41 ","pages":"Article 201322"},"PeriodicalIF":0.5,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics analysis for the identification of hub genes and Virtual screening of phytochemicals to inhibit AURKA in HepatoCellular carcinoma","authors":"Nandan Dixit ,&nbsp;Harsha Motwani ,&nbsp;Hiteshkumar A. Solanki ,&nbsp;Rakesh M. Rawal ,&nbsp;Saumya K. Patel","doi":"10.1016/j.humgen.2024.201321","DOIUrl":"10.1016/j.humgen.2024.201321","url":null,"abstract":"<div><p>HepatoCellular Carcinoma (HCC) is one of the most deadly and prevalent neoplasia, accounting for nearly 830,180 mortalities and 905,677 fresh occurrences worldwide annually. Aggressive malignancy with multifaceted etiologies increases in occurrence due to inadequate early diagnosis and ineffective treatment outcomes. Hence the present study aims to identify novel HCC associated biomarkers and inhibit the plausible genes through phytocompounds. Herein, we have implemented the meta-analysis of GSE36376, GSE57957 and GSE84598 micro-array profiles by utilizing GEO2R which resulted in identification of 1683 aberrantly expressed genes. The predicted DEGs were further subjected to Functional annotation and pathway enrichment analysis by using Blast2GO and ExpressAnalyst respectively. Successively, Protein-Protein Interaction analysis was performed by Cytoscape software, and the top 11 most significant hub nodes were identified. The most frequently occurring hub gene Aurora Kinase A (AURKA) was considered as plausible target for subsequent identification of inhibitors. The plant-derived small molecules retrieved from NPACT database were subjected to molecular docking, Molecular dynamic simulations and MMGBSA analysis against AURKA. Conclusively, findings from our study postulates Garcinone C and Silymarin targeting elevated AURKA levels which may contribute as potential inhibitors for HCC patients. However, these outcomes provide only computational insights for targeted HCC-therapeutics but for clinical application of Garcinone C and Silymarin <em>in vitro</em> and <em>in vivo</em> molecular validations are still warranted.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"41 ","pages":"Article 201321"},"PeriodicalIF":0.5,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the impact of deleterious nsSNPs on the MFSD1 protein","authors":"Sweta Nidhi ,&nbsp;Satish Kumar ,&nbsp;Aurosikha Das ,&nbsp;Abhishek Singh","doi":"10.1016/j.humgen.2024.201320","DOIUrl":"10.1016/j.humgen.2024.201320","url":null,"abstract":"<div><p>MFSD1 (Major facilitator superfamily domain containing 1) protein is a lysosomal multiple transmembrane-spanning protein responsible for the active transport of various compounds. Due to its potential role in maintaining liver homeostasis, any mutation might lead to altered protein expression, thus affecting the functionality. In this study, we explored the impact of deleterious nsSNPs (Nonsynonymous single nucleotide polymorphisms) on the stability, conformation, and functionality of the MFSD1 protein. SNP data and MFSD1 protein sequences were retrieved from NCBI dbSNP and Uniprot respectively. In total, five highly conserved nsSNPs were predicted to be deleterious based on their negative impact on the stability of the protein. Furthermore, the simulation analysis on the 3D structures of both native and mutant proteins revealed a notable impact on the physiological conformation of the protein. The identified variants not only affect the native conformation but also impact the association of MFSD1 with GLMP (Glycosylated Lysosomal Membrane Protein). In conclusion, the analysis revealed that the mutant protein's structural stability was inferior to that of the native protein. This research provides crucial insights for identifying and assessing MFSD1 mutations as potential diagnostic markers for liver-related diseases.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"41 ","pages":"Article 201320"},"PeriodicalIF":0.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}