Human Gene最新文献

{"title":"Minning of Immuno-mitotic and GABAergic genes as potential biomarkers of glioblastoma: An integrated transcriptomic analysis","authors":"","doi":"10.1016/j.humgen.2024.201336","DOIUrl":"10.1016/j.humgen.2024.201336","url":null,"abstract":"<div><p>Glioblastoma (GBM) is a highly lethal Central Nervous System (CNS) tumor prevalent in both adults and children, exhibiting elevated rates of mortality and morbidity. Due to the heterogenous nature of GBM, coupled with its nonspecific symptoms underscore the imperative for innovative biomarkers to enhance prognosis and the development of efficacious therapeutic interventions. This bioinformatics study seeks to elucidate the culprit genes, both up-regulated and down-regulated, within the context of their functional relevance, through a comparative analysis of gene expression profiles in GBM and normal brain tissues. Deregulated genes were identified from two Gene Expression Omnibus (GEO) datasets, employing the GEO2R tool to analyze expression data from normal and GBM tissues. Subsequently, differences in expression of genes (DEGs) through functional enrichment analysis were conducted by DAVID to discern their functional implications. Further, Protein-Protein Interaction (PPI) networks were constructed to identify hub genes among the selected up-regulated and down-regulated genes, employing various bioinformatics tools. The impact of the selected hub genes on patient overall survival was investigated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Notably, the up-regulated hub genes KIF2C and TTK exhibited significant correlations with overall survival, implicating their potential as immuno-mitotic biomarkers. Conversely, GAD2, the sole down-regulated hub gene, emerged as a promising molecular target for GBM, given its association with GABAergic signaling and amino acid metabolism. Consequently, these findings suggest that KIF2C and TTK may serve as immune-mitotic biomarkers, while GAD2 could be explored as a molecular target for GBM therapy. Nevertheless, additional research is essential to unravel the precise mechanistic underpinnings of GBM.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229786","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":"Liquid biopsy in brain tumors: Potential for impactful clinical applications","authors":"","doi":"10.1016/j.humgen.2024.201333","DOIUrl":"10.1016/j.humgen.2024.201333","url":null,"abstract":"<div><p>Despite the improvements in diagnostic and therapeutic techniques, heterogeneous constitution and non-invasive diagnosis remain major clinical challenges for brain tumors. In such a context, liquid biopsy is a noninvasive method that analyses tumor-derived biomarkers in body fluids and thus appears quite promising. This review explores the potential for circulating tumor cells, circulating tumor DNA, microRNAs, proteins, and exosomes as liquid biopsy markers in brain tumors. Although such biomarkers have potential for early detection, monitoring of disease progression, and guiding therapy, the limitations in the form of low levels of biomarkers and analytical complexities persist. Artificial intelligence integrated with liquid biopsy can therefore be expected to improve diagnostic accuracy and clinical utility. Further research, standardization, and clinical validation are needed to exploit the full potential of liquid biopsy in brain tumor management.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773044124000779/pdfft?md5=a38488b52d1ae0ec4f9454b7d9fb5e75&pid=1-s2.0-S2773044124000779-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of mutational features of colorectal cancer and multiple primary cancers including colorectal component: Data from the Cancer Genome Atlas","authors":"","doi":"10.1016/j.humgen.2024.201334","DOIUrl":"10.1016/j.humgen.2024.201334","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is the second in mortality among cancers with high incidence worldwide. About 5 % of patients had a previous oncopathology and 20 % develop a second malignancy. CRC molecular genetic mechanisms in primary multiple cancers (MPCs) are not fully understood. This study aimed to investigate mutational characteristics of primary CRC compared to MPCs with colorectal component. 336 CRC patients and 52 MPCs patients with a colorectal component (C97CRC) (TCGA-COAD data) were included. Comparative bioinformatics analysis of genetic mutations, their interactions, effect on signaling pathways, survival rate, and druggable categories was conducted. CRC was characterized by <em>PIK3CA</em> and <em>APC</em> mutations, while 17 mutations in other genes were identified in C97CRC. In CRC group, co-occurring somatic variants in <em>TP53/APC</em> and <em>KRAS/APC</em> were the most common, while in C97CRC, <em>KRAS/SOX9</em> was specifically found. <em>TP53</em>/<em>SYNE1</em>, <em>TP53</em>/<em>MUC16</em>, and <em>TP53/TTN</em> mutational combinations were associated with a decreased survival rate in CRC group. Collagen type VI α3-chain protease and its inhibitor were suggested as specific druggable targets in C97CRC group. The differences in mutational profiles between groups may indicate evolutionary features of CRC as a primary and secondary malignancy. Described druggable categories open up prospects for treatment development of CRC and MPCs with a colorectal component.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150724","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":"In silico analysis of the effects of non-synonymous SNPs associated with human GSK3B gene on its structure and function","authors":"","doi":"10.1016/j.humgen.2024.201332","DOIUrl":"10.1016/j.humgen.2024.201332","url":null,"abstract":"<div><p>Single Nucleotide Polymorphisms (SNPs) are abundantly identified by next generation sequencing (NGS) technology. Glycogen synthase kinase-3 beta (GSK3B), a widely expressed protein kinase, plays pivotal roles in cellular pathways. However, study on SNPs associated with GSK3B and their functional consequences is lacking. In this study, we analysed non-synonymous SNPs of GSK3B gene and their implications using computational tools. From NCBI dbSNP, 103,087 SNPs of GSK3B were initially gathered, later narrowed down to 255 unique nsSNPs. Around one-third of the nsSNPs resulted in charge and polarity change of the amino acids of the protein. 41 nsSNPs were found to significantly alter the stability of GSK3B protein (ΔΔG ≤ -1 or ≥ 1 kcal/mol) and few of them also affected the disorderness at the mutation site. Evolutionary conservation of the nsSNPs in the protein revealed 25 nsSNP may be deleterious to GSK3B protein function. Finally, 4 critical nsSNPs (Y161C, R167G, P225L and Y234D) were identified that can significantly alter both the stability and function of GSK3B. Furthermore, this study predicted 60 post-translational modification sites in GSK3B among which 26 sites contained nsSNPs. Interestingly, 7 upstream ORFs (uORFs) with high ribosomal occupancy were also detected in GSK3B mRNA that can reduce the expression of GSK3B protein. Altogether, this study has employed various in silico methods to characterize GSK3B nsSNPs, but they have limitations. These tools often overlook the cellular context, interacting partners, PTMs and the dynamic nature of proteins, which can affect protein behaviour and function. Despite these limitations, in silico tools are valuable for initial screening and prioritizing SNPs. The prioritized SNPs obtained in this study (Y161C, R167G, P225L and Y234D) should be experimentally validated using techniques like genome editing, biochemical assays, interactome analysis in cell lines and animal models to confirm their biological relevance.</p><p><strong>Clinical trial registration:</strong> Not Applicable.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128214","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 analysis of TRIOBP and MYO15A variants in Iranian families with autosomal recessive non-syndromic hearing loss","authors":"","doi":"10.1016/j.humgen.2024.201331","DOIUrl":"10.1016/j.humgen.2024.201331","url":null,"abstract":"<div><h3>Background</h3><p>Deafness is a prevalent sensory and neurological disorder that impacts over 466 million individuals globally. Congenital deafness is the most prevalent birth defect, occurring in approximately 2–3 out of every 1000 births. It is recognized as a highly diverse condition. &gt;50% of congenital deafness has genetic causes and the rest is due to environmental causes or both. With the development of next-generation sequencing and bioinformatics tools, whole-exome sequencing has been proposed as one of the effective methods for diagnosing genetics of hearing loss.</p></div><div><h3>Method</h3><p>Five Iranian Autosomal recessive non-syndromic hearing loss (ARNSHL) families negative for <em>GJB2</em> (NM_004004.6) gene mutations from Sistan and Baluchestan province were selected for further study by whole-exome sequencing analysis. The analysis procedure was performed using multiple bioinformatics tools and websites after filling the consent form and extracting DNA from whole blood using the salting out method. After detecting the variants in priority and confirming them in the probands by Sanger sequencing, other family members were studied to confirm the variant within the family.</p></div><div><h3>Results</h3><p>After analyzing the families recruited for this study, four known genes along with known and novel variants were discovered. Mutations found in the <em>MYO15A</em>, <em>SLC26A4</em>, <em>TRIOBP</em> and <em>TECTA</em> genes among which, the variants found in <em>TRIOBP</em> (NM_001039141.3, p.R283X) and <em>MYO15A</em> (NM_016239.4, p.P2880Rfs*19) were novel. Other known variants were <em>TECTA</em> (NM_005422.4, p.W1534X) and <em>SLC26A4</em> (NM_000441.2, p.V239D). No genes or variants that might contribute to hearing loss have been identified within one of the families.</p></div><div><h3>Conclusion</h3><p>Our study's findings support previous research that has identified <em>SLC26A4</em>, <em>MYO15A</em>, and <em>TECTA</em> genes as common genetic factors following <em>GJB2</em> in our population.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076433","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":"Valencene ameliorates ox-LDL induced foam cell formation by suppressing inflammation and modulating key proteins involved in the atherogenesis on THP-1 derived macrophages","authors":"","doi":"10.1016/j.humgen.2024.201330","DOIUrl":"10.1016/j.humgen.2024.201330","url":null,"abstract":"<div><p>Atherosclerosis is a distinct risk factor for cardiovascular and cerebrovascular disorders, which are significant contributors to global mortality. It is defined by macrophage-derived foam cell development followed by persistent inflammation, plaque formation, fibrosis and thrombosis. Studies have shown valencene, a sesquiterpene obtained from Valencia oranges, has several health-promoting properties. However, its protective effect against atherosclerosis and foam cell models remains unexplored. The present investigation revealed that valencene treatment suppresses foam cell generation and accumulation of lipids in THP-1-derived cells macrophage models activated with oxidized low-density lipoprotein (ox-LDL), maintained in vitro. The intracellular lipid content was qualitatively and semi-quantitatively analyzed by Oil Red O staining, and the compound's cytotoxicity was assessed through the MTT assay, considering both time-dependent and dose-dependent factors. The RT-qPCR results showed promising anti-inflammatory and anti-oxidant enzyme status upon valencene treatment. The H2DCFDA staining revealed valencene's ability to reduce the oxidative stress induced by ox-LDL. Further, high-throughput proteomic profiling was carried out to identify the target proteins affected by valencene treatment and thereby explore its mechanism of action on foam cell models. Proteomic studies revealed that valencene treatment regulates the expression of several proteins associated with ox-LDL-induced inflammation, defective cholesterol homeostasis and cholesterol efflux pathways.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050307","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":"Identification of overlapping molecular mechanisms in tuberculosis and sarcoidosis: A bioinformatics approach","authors":"","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":null,"pages":null},"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":"","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":null,"pages":null},"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":"","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":null,"pages":null},"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":"","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":null,"pages":null},"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}