Human Gene最新文献

{"title":"Knockdown of histone H1–5 gene affects the sensitivity of MRC-5 and HeLa cells to DNA damaging agents","authors":"Tigran Harutyunyan ,&nbsp;Anzhela Sargsyan ,&nbsp;Gohar Tadevosyan ,&nbsp;Lily Kalashyan ,&nbsp;Rouben Aroutiounian ,&nbsp;Galina Hovhannisyan","doi":"10.1016/j.humgen.2025.201475","DOIUrl":"10.1016/j.humgen.2025.201475","url":null,"abstract":"<div><div>Linker histone H1.5, encoded by the <em>H1–5</em> gene, plays a key role in chromatin compaction and genome stability. However, its role in cellular responses to mutagens is still poorly understood. Here, we analyzed the genotoxic effects of the standard genotoxic drugs doxorubicin (DOX) and mitomycin C (MMC) at non-cytotoxic concentrations after 24 h of treatment in normal lung fibroblasts (MRC-5) and cervical carcinoma cells (HeLa) with <em>H1–5</em> gene knockdown (KD). Using CRISPR-Cas9, we achieved significant repression of <em>H1–5</em> expression. Alkaline DNA comet assay and cytokinesis-block micronucleus assay showed that <em>H1–5</em> KD significantly increased spontaneous and mutagen-induced DNA and chromosome damage levels in both cell lines (<em>p</em> &lt; 0.05). Our results suggest that <em>H1–5</em> gene deficiency makes DNA more susceptible to genotoxic impact while its mechanistic role in occurrence of DNA and chromosome damage requires further elucidation.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201475"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094985","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":"Single-cell transcriptomics exposes an uncharacterized lncRNA governing colorectal cancer metastasis","authors":"Abbas Heydari Lori ,&nbsp;Nahid Askari ,&nbsp;Hossein Pourghadamyari","doi":"10.1016/j.humgen.2025.201479","DOIUrl":"10.1016/j.humgen.2025.201479","url":null,"abstract":"<div><div>Colorectal cancer (CRC) exhibits significant molecular heterogeneity, with long non-coding RNAs (lncRNAs) playing crucial regulatory roles. This study identifies <em>LncRNA01996</em> as a key oncogenic driver upregulated in CRC tumors compared to adjacent normal tissues, with expression levels correlating directly with advancing cancer stage (Stage I to IV). Mechanistically, <em>LncRNA01996</em> stabilizes β-catenin, hyperactivating the Wnt signaling pathway while simultaneously suppressing <em>E-CADHERIN</em> expression a critical factor in maintaining cellular adhesion. This dual action promotes cancer cell invasion and metastasis. Additionally, <em>LncRNA01996</em> transcriptionally activates MYC, amplifying its oncogenic effects.</div><div>Clinically, high <em>LncRNA01996</em> expression is linked to aggressive tumor features, elevated serum markers (CEA, CA19–9), and shorter overall survival in patients. These findings were consistent across patient tissues, cell lines (SW480, SKM), and single-cell RNA sequencing data, confirming its role in diverse CRC microenvironments.</div><div>In summary, <em>LncRNA01996</em> drives CRC progression by dysregulating Wnt/β-catenin signaling, disrupting cell adhesion, and amplifying <em>MYC</em>-driven malignancy. Its strong association with advanced disease and poor outcomes positions <em>LncRNA01996</em> as a promising prognostic biomarker and a compelling therapeutic target for intercepting CRC metastasis.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201479"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094986","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":"Mapping the transcriptional architecture of glioblastoma at the single-cell level: Decoding heterogeneity, angiogenesis, and mesenchymal shifts","authors":"Naureen Mallick,&nbsp;Reaz Uddin","doi":"10.1016/j.humgen.2025.201467","DOIUrl":"10.1016/j.humgen.2025.201467","url":null,"abstract":"<div><div>Glioblastoma (GBM), a grade IV glioma, is the most aggressive and fatal primary brain tumor, accounting for 48 % of all Central Nervous System tumors. Despite advancements in therapeutic strategies, GBM remains highly resistant to treatment, with a median survival time of just 14 months. This study aimed to identify molecular signature genes associated with GBM heterogeneity using scRNA-seq datasets from 10× Genomics. Two scRNA-seq datasets were processed through the Cell Ranger pipeline, followed by quality control, normalization, and scaling. After data integration using R, Principal Component Analysis was performed, and clusters were visualized using UMAP. A total of 2772 DEGs were identified, of which 95 DEGs met the threshold of logFC≥4 and p-adj ≤ 0.05. These DEGs were significantly enriched in angiogenesis and the PI3K signaling pathway, associated with poor prognosis. Principal Component Analysis revealed 15 principal components, with the first four accounting for the greatest variance. UMAP clustering identified 13 distinct cell clusters, which were annotated using the HPCA reference dataset, revealing enrichment in astrocytes, immune cells, and other tumor-associated cell types. A PPI network was constructed using the STRING database and visualized in Cytoscape, leading to the identification of three mesenchymal hub genes—KDA, PDGFRB, and CXCL12—as key angiogenic markers in GBM. The identified DEGs and hub genes were further validated using GEPIA2 and GSEA. This study provides novel insights into GBM heterogeneity and angiogenic biomarkers, potentially guiding future therapeutic strategies. Nevertheless, additional experimental validation is required to fully understand their role in GBM pathogenesis.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201467"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887251","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":"Deciphering the risk of missense mutation rs137854486 (W1925R) of FN1 in papillary thyroid cancer: A computational and molecular dynamics approach","authors":"Febby Payva ,&nbsp;Remya James ,&nbsp;Amrisa Pavithra E. ,&nbsp;Padmashree Das ,&nbsp;Santhy K.S.","doi":"10.1016/j.humgen.2025.201484","DOIUrl":"10.1016/j.humgen.2025.201484","url":null,"abstract":"<div><div>Papillary thyroid cancer (PTC) accounts for more than 85 % of all thyroid cancers. Three transcriptomic datasets of PTC, one each from humans (GSE138198), transgenic mice (GSE58689), and cell lines (GSE6339), were analysed for differentially expressed genes (DEGs). Seventy-three common DEGs were binned into significant pathways associated with cancer and immunity, for which gene ontology studies at the biological process, molecular function, and cellular component levels were performed. Protein–protein interaction (PPI) network construction and analysis of modules identified fibronectin 1 (FN1) as the critical hub gene in the pathophysiology of PTC. Survival analysis, immune infiltration analysis, and co-expression analysis of the hub genes were conducted to confirm their relationship with PTC prognosis. Analysis of four missense variants V692E, T817A, T817P and W1925R of FN1 associated with PTC, followed by structural analysis and molecular dynamics simulation, validated that the missense mutation rs137854486 (W1925R) of FN1 is significant in the tumorigenesis of PTC. FoldX predicted a significant positive ΔΔG (9.85646) value for W1925R, portraying substantial destabilization of FN1. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) values of the W1925R mutant indicate significant structural deviations in the protein, resulting in increased flexibility and reduced stability. Increased flexibility, particularly in regions critical for protein function, could affect the biological activity of the protein, with a crucial influence on the pathophysiology of PTC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201484"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219091","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":"LiqBiMark: An advanced bioinformatics pipeline for integrative transcriptomic analysis and identification of non-invasive prognostic biomarkers using GEO datasets","authors":"Amir Mohammad Mazhari ,&nbsp;Farshad Safaei ,&nbsp;Mahsa Torkamanian-Afshar ,&nbsp;Ali Najafi","doi":"10.1016/j.humgen.2025.201490","DOIUrl":"10.1016/j.humgen.2025.201490","url":null,"abstract":"<div><h3>Background</h3><div>The Gene Expression Omnibus (GEO) database was established by the National Center for Biotechnology Information (NCBI) to facilitate sharing molecular biology data. This repository hosts numerous datasets related to complex diseases such as cancer, generated by researchers worldwide. One of the most challenging issues is finding non-invasive biomarkers in the vast amount of data deposited in public databases related to a specific type of cancer.</div></div><div><h3>Results</h3><div>To address this issue, we have designed a Liquid Biopsy Biomarker Discovery (LiqBiMark) pipeline that compares two datasets on the same type of cancer, but with different sample sources, to propose potential biomarker candidates. Additionally, the LiqBiMark generates co-expression networks and conducts clustering analysis.</div></div><div><h3>Conclusions</h3><div>The pipeline is designed to be accessible even to users with minimal experience, allowing them to obtain results quickly and efficiently.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201490"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319600","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":"Adiponectin gene polymorphism and TyPE 2 diabetes MellitUS: Contrasting genetic RISKS in overdominant vs recessive and allele models – an updated meta – analysis","authors":"Santhini Gopalakrishnan ,&nbsp;Santhi Priya Sobha ,&nbsp;Karpagavel Lakshmanan","doi":"10.1016/j.humgen.2025.201463","DOIUrl":"10.1016/j.humgen.2025.201463","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder and adipokines such as adiponectin plays a crucial role in the development of T2DM. Adiponectin is encoded by APM1/ADIPOQ gene and polymorphism has been associated with T2DM. The present study aims to determine the overall effect of major SNP of adiponectin gene with T2DM risk.</div></div><div><h3>Methods</h3><div>A through literature search was conducted to identify suitable studies and data was extracted. The association of SNP with T2DM was determined using odds ratio (OR) with 95 % C.I.</div></div><div><h3>Result</h3><div>Allele contrast and recessive model of rs16861194(−11426 A &gt; G), rs266729(−1137C &gt; G), rs2241766(+45 T &gt; G), rs17300539(−11,391 G &gt; A) and rs822396(−3971 G &gt; A) genotype of the APM1/ADIPOQ gene was associated with reduced T2DM risk. The African and Asian population subgroup demonstrated lower T2DM risk under allele contrast and recessive model of rs16861194 and rs2241766 while Caucasian was associated with reduced risk in recessive model of rs266729. The rs822396 variant demonstrated lower risk under allele contrast and recessive model in Asian subgroup. The rs2241767(+346 A &gt; G) polymorphism was associated with reduced T2DM risk under allele contrast and in subgroup analysis only African population showed significant association. In contrast, the over dominant model was associated with increased T2DM risk in rs16861194, rs266729, rs182052, rs2241766, rs17300539 and rs822396. The African and Asian ethnicity demonstrated an increased risk in over dominant model with rs16861194 and rs2241766 while Asian ethnicity showed significant association under over dominant model in rs182052 and rs822396. The rs3774261(+712 A &gt; G) and rs1501299(+276G &gt; T) showed no association with T2DM risk.</div></div><div><h3>Conclusion</h3><div>The major polymorphism of adiponectin showed increased risk under overdominant model while showed a reduced risk under allele and recessive genetic model.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201463"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879614","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":"Novel nonsense mutation in MYH6 gene identified as the cause of familial hypertrophic cardiomyopathy – A case report and literature review","authors":"Chenxi Liu ,&nbsp;Wen Wen ,&nbsp;Zheng Zhang","doi":"10.1016/j.humgen.2025.201504","DOIUrl":"10.1016/j.humgen.2025.201504","url":null,"abstract":"<div><div>This study reports a familial hypertrophic cardiomyopathy (HCM) case caused by the MYH6 c.5467G &gt; T (p. Glu1823Ter) nonsense variant. The proband, a 44-year-old male, presented with sudden-onset chest pain and dyspnea. Echocardiography revealed left atrial enlargement, asymmetric septal hypertrophy, and left ventricular outflow tract obstruction, while cardiac magnetic resonance imaging demonstrated mid-septal delayed enhancement, confirming HCM diagnosis. Genetic analyses via next-generation sequencing (NGS) and Sanger sequencing identified a heterozygous nonsense variant (c.5467G &gt; T) in the MYH6 gene, predicted to induce nonsense-mediated mRNA decay (NMD). Three-generation pedigree analysis showed complete co-segregation of this variant with HCM phenotype. Mutation carriers exhibited varying degrees of HCM, whereas non-carriers had normal cardiac structures. These findings suggest the MYH6 c.5467G &gt; T variant as a contributor to HCM development.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201504"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465899","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 convergence and diversity: A comparative analysis of Egyptian autosomal STR profiles within global populations","authors":"Sagy Elzalabany ,&nbsp;Ibrahim H. Aboughaleb ,&nbsp;Mohamed Hisham Fouad Aref ,&nbsp;Tarek Taha ,&nbsp;Khaled Amer ,&nbsp;Sahar Fawzi ,&nbsp;Olfat Shaker","doi":"10.1016/j.humgen.2025.201472","DOIUrl":"10.1016/j.humgen.2025.201472","url":null,"abstract":"<div><h3>Background and objective</h3><div>Short Tandem Repeats (STRs) are widely used genetic markers for forensic identification and population genetics due to their high polymorphism. Given Egypt's unique position at the crossroads of Africa, Asia, and Europe, this study aims to analyze the allele frequency distribution of 15 autosomal STR loci in Egyptians and assess their genetic affinities with over 60 other global populations. The objective is to characterize Egypt's genetic profile, evaluate its intra- and inter-regional relationships, and contribute to a broader understanding of global STR clustering.</div></div><div><h3>Methods</h3><div>Allele frequency data for 15 autosomal STR loci were collected for the Egyptian population and compared with datasets from diverse global populations using Pearson's correlation coefficients, FST genetic distances, and Nei's genetic distance. Hierarchical clustering (UPGMA), allele frequency trajectories (AFTs), and Principal Coordinates Analysis (PCoA) were used to visualize genetic relationships. The findings were contextualized with prior studies of regional genetic structure for completeness and accuracy.</div></div><div><h3>Results</h3><div>The Egyptian STR profile showed moderate to high correlation (<em>r</em> &gt; 0.85) with Middle Eastern, North African, and Southern European populations. FST and Nei's genetic distance values placed Egypt at a transitional point between Sub-Saharan African and Eurasian clusters. AFT plots revealed several loci with population-specific allele shifts, consistent with historical migration and admixture patterns. Notably, the results aligned with Omran et al.'s finding of genetic divergence between Northern and Southern Egyptians, and supported the tripartite global clustering model described in the 2014 worldwide STR analysis.</div></div><div><h3>Conclusions</h3><div>Egypt exhibits a unique genetic signature that reflects both African and Eurasian contributions, supporting its role as a genetic bridge population. These findings are valuable for forensic databases, population history, and anthropological studies. Future research should incorporate genome-wide SNP and uniparental marker analyses to further explore Egypt's internal diversity and its broader genetic connections.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201472"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044052","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":"Association of transmembrane 6 superfamily member 2 rs 58542926, rs 187429064, rs 142056540, rs 72999063, rs 72999068 and rs 2074299 with susceptibility of metabolic dysfunction-associated steatotic liver disease in Bangladeshi population","authors":"Md Kamal Hossain Ripon ,&nbsp;A.K. Azad Chowdhury ,&nbsp;Mamun Al-Mahtab ,&nbsp;Zobaer Al Mahmud ,&nbsp;Nahid Sharmin ,&nbsp;Sheikh Zahir Raihan","doi":"10.1016/j.humgen.2025.201502","DOIUrl":"10.1016/j.humgen.2025.201502","url":null,"abstract":"<div><div>Polymorphism of the transmembrane 6 superfamily member 2 (<em>TM6SF2</em>) gene influences the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). It is unclear how <em>TM6SF2</em> is related to the consequence of MASLD in the Bangladeshi people. This case-control study aims to determine whether the polymorphism in the <em>TM6SF2</em> gene is linked with MASLD subjects in Bangladesh. Genomic DNA was isolated from peripheral blood samples. Sanger sequencing was completed for the genotype of single nucleotide polymorphisms (SNPs). SPSS was used to analyze the data for statistics. A total of 138 Bangladeshi people participated in the study. Binary logistic regression assisted in determining the link between MASLD and genetic variants. The MASLD group had a significantly higher minor allele frequency in the rs 58542926 (T), rs 72999063 (T) and rs 72999068 (G) of <em>TM6SF2</em> compared to the healthy controls (<em>P</em> = 0.018, &lt;0.001, 0.001, respectively). After adjusting for age and gender, the dominant model of rs 58542926 moderately elevated the risk of MASLD (OR: 3.29, 95 % CI: 1.00–10.89; <em>P</em> = 0.051). In our study group, rs 72999063, rs 72999068 and rs 2074299 were not found to have any significant effect on the risk of developing MASLD after adjusting for age, gender and rs 58542926. However, polymorphism rs 58542926 was found to be moderately LD (linkage disequilibrium) with both rs 72999063 and rs 72999068 (D′ = 0.804, <em>r</em> = 0.597, <em>P</em> &lt; 0.05 and D′ = 0.746, <em>r</em> = 0.611, <em>P</em> &lt; 0.05, respectively). Whereas rs 72999063 and rs 72999068 are strongly LD together with D′ = 0.999 and <em>r</em> = 0.904, <em>P</em> &lt; 0.05. This study will help identify rs 58542926, rs 72999063, and rs 72999068 polymorphisms of <em>TM6SF2</em> in various global populations. Further analyses are needed to better understand the effects of the <em>TM6SF2</em> polymorphism on MASLD susceptibility, including a larger sample size and more physiological details.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201502"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465872","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":"YES1 c.596C>T (p.Arg199His) and YES1 c.868C>T (p.Glu290Lys) missense polymorphism linked to hematological and reproductive organ cancer: A hidden Markov model (HMM) based approach","authors":"Raushan Kumar Chaudhary ,&nbsp;Allen Pinto ,&nbsp;Niyas Rehman ,&nbsp;Debodipta Das ,&nbsp;Rajesh Raju","doi":"10.1016/j.humgen.2025.201487","DOIUrl":"10.1016/j.humgen.2025.201487","url":null,"abstract":"<div><div><em>YES1</em> is a novel proto-oncogene that has largely gained popularity in oncology over the last few years owing to its pivotal role in tumorigenesis, and drug resistance to various targeted therapy (<em>EGFR, HER2</em>) and cancer chemotherapy, resulting in poor survival outcomes, which has been frequently linked with its amplification rather than the mutation. Thus, this study hypothesizes that cancer development might also be linked with a mutation in <em>YES1,</em> not merely amplification of the gene. In the present study, <em>YES1</em> gene-associated missense SNPs were retrieved from the dbSNP-NCBI database, which were screened for deleterious/damaging and pathogenicity. The pathogenic SNPs were assessed for their stability and potential to cause cancer. The oncogenic SNPs were further evaluated for its location in the domain, conservation, structural effect, and interactions. Further, <em>YES1</em> expression in cancer, its hallmark efficiency and mutation in cancer was assessed to support the study findings. A total of 381 SNPs were identified from dbSNP-NCBI of which 7 SNPs were found to be deleterious, damaging and pathogenic by applying six tools. Out of these 7 SNPs, <em>YES1 c.596C</em> <em>&gt;</em> <em>T (p.Arg199His)</em> and <em>YES1 c.868C</em> <em>&gt;</em> <em>T (p.Glu290Lys)</em> were predicted destabilize the protein and associated with blood cancer, and solid cancer like reproductive organ cancer, and gastrointestinal (GI) cancer respectively. Both these oncogenic SNPs occurs in core biologically active conserved domain (SH2 and tyrosine kinase) of <em>YES1</em> protein thereby influences the protein geometry, electrostatic interaction, impairs the ATP/substrate binding and kinase activity of the protein which might dysregulate the protein-protein interaction and modulate various cancer pathways. Further, its significant expression in cancer (hematologic, reproductive and GI cancer), role in driving invasion/metastasis, and evidence of <em>YES1</em> mutation profile in cancer cohort strengthen the findings of current study. Thus, R199H and E290K SNPs are the most probable SNPs that should be screened among cancer patients to establish a plausible link which can guide towards the precision therapy to counter the drug resistance and enhance the clinical benefit in upcoming years.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201487"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265458","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}