Human Gene最新文献

{"title":"High-throughput genomic profiling in chronic myelogenous leukemia: How far have we come, and what lies ahead?","authors":"Laras Pratiwi ,&nbsp;Galih Januar Adytia ,&nbsp;Henry Sutanto","doi":"10.1016/j.humgen.2025.201425","DOIUrl":"10.1016/j.humgen.2025.201425","url":null,"abstract":"<div><div>Chronic Myelogenous Leukemia (CML) is a hematological malignancy characterized by the <em>BCR::ABL1</em> fusion gene, a hallmark of its pathogenesis. Advances in molecular biology and genomic technologies have significantly enhanced our understanding of CML, with Next-Generation Sequencing (NGS) emerging as a potential transformative tool in the field. This review explores the expanding role of NGS in the diagnosis, prognostic stratification, and treatment monitoring of CML. By enabling comprehensive genomic profiling, NGS facilitates the identification of genetic mutations and clonal evolution, offering insights beyond traditional diagnostic methods. Additionally, the application of NGS in detecting treatment-resistant mutations and monitoring minimal residual disease (MRD) underscores its utility in tailoring precision therapies. However, challenges such as technical complexities, integration into clinical workflows, and cost constraints remain barriers to widespread adoption. This review highlights the clinical implications of NGS in CML management and discusses future directions, including emerging sequencing technologies and potential synergies with advanced analytics. As NGS continues to evolve, its role in shaping personalized medicine and improving patient outcomes in CML is becoming increasingly evident. This review provides a comprehensive overview of these developments while addressing the current limitations and opportunities for future research.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201425"},"PeriodicalIF":0.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116522","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 case of Cockayne syndrome with two novel mutations in the ERCC6 gene: Expanding the phenotypic and genetic spectrum","authors":"Xinyao Wang,&nbsp;Lingzhao Min,&nbsp;Jia Wei,&nbsp;Xiaoqiang Wang","doi":"10.1016/j.humgen.2025.201420","DOIUrl":"10.1016/j.humgen.2025.201420","url":null,"abstract":"<div><div>A one-year-old East Asian boy presented with significant growth and developmental delays, including microcephaly, poor motor development, and feeding difficulties. He also exhibited poor visual and auditory tracking, along with occasional vomiting and skin vulnerability to sun exposure. Cranial CT revealed cortical dysplasia and a septum pellucidum cyst. Whole exome sequencing identified three heterozygous mutations in the ERCC6(Excision repair cross-complementation group 6) gene: two novel mutations (c.1557G &gt; A and c.1821 + 1del) inherited from the father and mother, respectively, and a third mutation (c.1820 A &gt; T) with uncertain pathogenicity, also inherited from the mother. The genetic findings led to a diagnosis of Cockayne syndrome, contributing to the expanding knowledge of the ERCC6 gene mutation spectrum and aiding in the clinical diagnosis and genetic counseling for the family. This case underscores the importance of accurate genetic diagnosis in managing prognosis and providing counseling for high-risk families.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201420"},"PeriodicalIF":0.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203170","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":"Investigating the effect of Lactobacillus crispatus extract on the expression of Axin2 and GSK3β genes from Wnt pathway in uterine cell line","authors":"Zahra Fazeli ,&nbsp;Farkhondeh Pouresmaeili ,&nbsp;Masoumeh Azimirad ,&nbsp;Armitasadat Emami ,&nbsp;Azadeh Aarabi ,&nbsp;Sunbul Muradi ,&nbsp;Abbas Yadegar ,&nbsp;Seyed Farhad Sadr Tabatabaie","doi":"10.1016/j.humgen.2025.201417","DOIUrl":"10.1016/j.humgen.2025.201417","url":null,"abstract":"<div><h3>Introduction and aim</h3><div>The Wnt1 signaling pathway is recognized for its involvement in cell growth as well as its capacity to trigger apoptosis. A variety of research has underscored the effect of Lactobacillus populations on uterine health, especially in the context of embryo implantation. This study seeks to explore how bacillus extracts affect the expression of Wnt1 genes in the context of recurrent miscarriage, with a particular emphasis on endometrial stem cells (ENSC).</div></div><div><h3>Material and method</h3><div>A preparation of <em>Lactobacillus crispatus</em> extract was created, and the ENSC cell line was grown in specialized media containing different concentrations of the bacterial extract and subjected to various incubation times. Total RNA was isolated from the cultured cells, which was then used to synthesize cDNA. Real-time PCR was performed with specific primer pairs targeting Axin2 and GSK3β, in addition to amplifying a suitable housekeeping gene for uterine tissue. The results were evaluated using SPSS and LinReg software.</div></div><div><h3>Results</h3><div>The application of the crispatus extract to the ENSC cell line led to a notable increase in the expression of Axin2, whereas GSK3β demonstrated a non-significant rise within the Wnt1 pathway (<em>p</em> value = 0.001). It was observed that the bacterial extract displayed a quantifiable level of cytotoxicity at elevated concentrations. The findings revealed that the expression of the Axin2 gene was significantly greater than that of GSK3β (p value = 0.001). No significant changes in gene expression were observed in the untreated ENSC cell lines.</div></div><div><h3>Conclusion</h3><div>A more comprehensive insight into the effects of bacterial extracts on the active genes involved in biochemical pathways within endometrial tissue could aid in the formulation of probiotic approaches and therapies for recurrent miscarriage, as these genes play a significant role in this condition.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201417"},"PeriodicalIF":0.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139061","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 variants in MTHFR and PAI-1 genes and their influence on miscarriage risk in the Iranian population","authors":"Mahsa Sadr ,&nbsp;Bita Naemi ,&nbsp;Majid Tafrihi ,&nbsp;Reza Jafarzadeh Esfehani","doi":"10.1016/j.humgen.2025.201416","DOIUrl":"10.1016/j.humgen.2025.201416","url":null,"abstract":"<div><h3>Introduction</h3><div>Spontaneous abortion is a multifactorial condition, with genetic polymorphisms being one of the proposed contributing factors. This study aimed to evaluate the association between <em>MTHFR</em> A1298C, <em>MTHFR</em> C677T, and <em>PAI-1</em> gene polymorphisms and spontaneous abortion.</div></div><div><h3>Materials and methods</h3><div>This case-control study included women with history of abortion as case group and a similar group with the same size as healthy controls. Genotype distributions of <em>MTHFR</em> A1298C, <em>MTHFR</em> C677T, and <em>PAI</em> were determined using sanger sequencing technique. Statistical analyses included chi-square tests to compare genotype distributions and logistic regression to assess the predictive value of these polymorphisms on abortion outcomes were considered and generalized linear model evaluated the impact of genotypes on the number of abortions.</div></div><div><h3>Results</h3><div>Total number of 250 women included in the case group with the mean age of 31 ± 6.5 years. Significant differences in genotype distributions were observed for <em>MTHFR</em> A1298C (<em>p</em> = 0.037) and <em>PAI</em> (<em>p</em> = 0.001) between case and control groups, suggesting their association with pregnancy loss. However, <em>MTHFR</em> C677T showed only a marginal association (<em>p</em> = 0.062). Despite these differences, regression analysis revealed no significant effects of these genotypes on the likelihood or number of abortions (<em>p</em> &gt; 0.05). Generalized linear model analysis also confirmed no significant contributions of these polymorphisms to abortion outcomes.</div></div><div><h3>Conclusion</h3><div>While <em>MTHFR</em> A1298C and <em>PAI</em> polymorphisms are associated with pregnancy loss, their independent predictive value appears limited. These findings underscore the complex, multifactorial nature of pregnancy loss and highlight the need for further research to explore gene-gene and gene-environment interactions in understanding its etiology.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201416"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090264","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":"Common biomarker genes associated with cardiovascular disease and diabetes mellitus: Implications for cross-disease therapeutic strategies and Cancer prognosis","authors":"Mahir Azmal,&nbsp;Jibon Kumar Paul,&nbsp;Tasnim Alam,&nbsp;Omar Faruk Talukder,&nbsp;Mohua Mrinmoy,&nbsp;A.N.M. Shah Newaz Been Haque,&nbsp;Ajit Ghosh","doi":"10.1016/j.humgen.2025.201418","DOIUrl":"10.1016/j.humgen.2025.201418","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) and diabetes mellitus (DM) are two prevalent chronic diseases that share interconnected risk factors, including chronic inflammation and metabolic dysfunction. Recent studies have identified molecular links between these conditions and cancer, indicating shared pathways in inflammation and immune responses. The objective of this study is to identify potential biomarkers shared between CVD and DM; and to explore their relevance in cancer prognosis. By examining these biomarkers, the study aims to uncover common molecular mechanisms that may link CVD, DM, and cancer, providing insights into potential therapeutic targets and cross-disease pathways that could inform clinical approaches for these interconnected diseases. To identify common biomarker genes associated with CVD and DM using bioinformatics analysis, six gene expression datasets from the NCBI GEO database were employed. Differential gene expression analysis revealed 90 common genes between CVD and DM. Furthermore, the dataset was individually analyzed with Cytoscape, and the 24 key biomarkers were identified using Cytohubba and MCODE. Pathway and GO ontology analysis was performed for the correlation with other diseases, and the common key upregulated biomarkers, IL6, CCR1, and CCR2, were identified for their significant roles in inflammation and immune responses. Pathway analysis revealed the involvement of these genes in the IL6 signaling, TNF signaling, and chemokine-mediated pathways. Further expression analysis demonstrated the upregulation of IL6 in lung cancer subtypes and CCR1 in breast cancer, indicating a possible link to cancer progression. Additionally, survival analysis showed that high CCR1 expression was associated with poor survival outcomes in cancer patients.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201418"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068459","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 circulatory hsa-miR-146a-5p and hsa-miR-192-5p with impaired fasting glycaemia in HIV infected subjects","authors":"K. Karthik ,&nbsp;Pratibha Misra ,&nbsp;R. Palaniswamy ,&nbsp;Leena Rawat ,&nbsp;Anurodh Gupta ,&nbsp;Bhasker Mukherjee ,&nbsp;G. Ankita ,&nbsp;G. Ruchira ,&nbsp;M.K. Sibin","doi":"10.1016/j.humgen.2025.201421","DOIUrl":"10.1016/j.humgen.2025.201421","url":null,"abstract":"<div><h3>Background</h3><div>hsa-miR-146a-5p and hsa-miR-192-5p were associated with pre diabetes and type 2 diabetes mellitus in HIV negative individuals. However, no study reported their expression in prediabetes condition associated with HIV infected subjects undergoing anti-retroviral therapy (ART).</div></div><div><h3>Methods</h3><div>Circulatory hsa-miR-146a-5p and hsa-miR-192-5p expressions were measured in HIV positive subjects undergoing ART with impaired fasting glycemia (IFG) and with normoglycemia (36 in each group).</div></div><div><h3>Results</h3><div>There was overexpression of hsa-miR-146a-5p and hsa-miR-192-5p in serum samples of HIV infected subjects on ART with IFG when compared to their normoglycemic counterparts. Both miRNAs showed diagnostic utility in ROC curve analysis to detect IFG in HIV positive subjects on ART.</div></div><div><h3>Conclusion</h3><div>Present study for the first time showed the differential expression of hsa-miR-146a-5p and hsa-miR-192-5p in IFG associated with HIV infected subjects on ART. We have also shown their diagnostic utility in these patients. However, larger cohort studies are warranted to validate the results of this pilot study.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201421"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090339","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":"The new inheritance of Leber Congenital Amaurosis with heterozygous AIPL1 gene mutation: A case report","authors":"Pegah Ghavidel ,&nbsp;Reza Salmanipour ,&nbsp;Golnoosh Salehi ,&nbsp;Behnoush Sohrabi ,&nbsp;Massoud Houshmand","doi":"10.1016/j.humgen.2025.201413","DOIUrl":"10.1016/j.humgen.2025.201413","url":null,"abstract":"<div><h3>Background</h3><div>Leber congenital amaurosis (LCA) is the earliest onset and most severe form of hereditary retinal dystrophy. Mutations in at least 25 different genes are associated with LCA and have critical roles for normal retinal function. <em>AIPL1</em> gene is defined to associate with LCA4 which is one of the most clinically severe forms. The frequency of <em>AIPL1</em> variants is 5.3 % among LCA patients in different populations worldwide. In this study, we report new inheritance of LCA with heterozygous of <em>AIPL1</em> gene mutation.</div></div><div><h3>Case report</h3><div>We report a child boy with poor vision in both eyes, cycloplegic refractions, hyperopia in oculus dextrus and oculus sinister, natural eyelids, vertical nystagmus, salt pepper pigmentation retinopathy and night vision problems feature from a consanguineous marriage with a new inheritance of LCA with heterozygous <em>AIPL1</em> gene mutation (c: 834G &gt; A) by using whole exome sequencing.</div></div><div><h3>Conclusion</h3><div>Identification a new hereditary pattern of gene mutations involved in the development of LCA disease can play an important role in preventing the birth of children with this disease. This case report describes a new inheritance of LCA disease with heterozygous <em>AIPL1</em> gene mutation (c: 834G &gt; A, p. Trp278*) to form of autosomal dominant in child boy from Iran. Individuals who carry c: 834G &gt; A (p. Trp278*) mutation of <em>AIPL1</em> gene should be considered patients. Therefore, the necessary recommendations should be given before pregnancy by a genetic counselor to couples at risk of having a child with LCA disease.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201413"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916900","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 beta-arrestin gene expression with corticosteroids -long-acting beta-agonist step-up therapy in children with asthma","authors":"Manoj Kumar ,&nbsp;Ambika Sharma ,&nbsp;Poonam Katoch ,&nbsp;Vikas Kaushal ,&nbsp;Anil Chauhan ,&nbsp;Savita Verma Attri ,&nbsp;Inusha Panigrahi ,&nbsp;Madhu Khullar ,&nbsp;Meenu Singh","doi":"10.1016/j.humgen.2025.201414","DOIUrl":"10.1016/j.humgen.2025.201414","url":null,"abstract":"<div><h3>Background</h3><div>Beta2-adrenergic receptors (β₂-ARs) mediate airway relaxation through cAMP-dependent and cAMP-independent pathways. Studies have shown the existence of alternative β-arrestin mediated pathways, downstream of β₂-AR that play a role in inflammation. The higher β-arrestin expression is linked to the attenuation of agonist induced broncho dilating signaling pathways in human airway smooth muscle cells. The Long-acting beta-agonists (LABAs) are the preferred approach to inhaled corticosteroids (ICS). LABAs act on β₂-ARs in bronchial smooth muscles and cause bronchodilation. The ICS/LABA therapy provides synergistic effects in asthma control that are not achieved by any of them alone. Despite this, a subset of patients remains symptomatic of the treatment. Deterioration of asthma control can be due to β-arrestin-dependent pathways and the effects of ICS/LABA therapy on β-arrestin expression have not been explored.</div></div><div><h3>Methods</h3><div>The study included 76 asthmatic children taking ICS-LABA therapy and 29 healthy children with no respiratory disease and family history of asthma. After excluding Children with ABPA, 70 asthmatic children were categorized into responders and non-responders. The gene expression of β-arrestin1 &amp;2 gene was analyzed.</div></div><div><h3>Results</h3><div>Among the 70 subjects 34 were responders and 36 were non-responders. β-arrestin 1 mRNA expression was significantly higher in the non-responder's group as compared to healthy controls [3.3 (1.46–6.19) vs 0.72 (0.4–3.4); <em>p</em> = 0.002]. No significant difference was observed in β-arrestin2 mRNA expression among all groups.</div></div><div><h3>Conclusions</h3><div>β-arrestin-1 gene expression can be associated with symptomatic conditions in patients. Studies with large sample sizes are required in steroids-resistant asthma to explore the link between β-arrestin and asthma.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201414"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924478","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 polymorphisms and expression levels in miRNA and their contribution to pediatric acute myeloid leukemia: A focus on miR-146a and miR-499 variants","authors":"Saeedeh Ghazaey Zidanlo ,&nbsp;Danial Jahantigh ,&nbsp;Nafiseh Amini","doi":"10.1016/j.humgen.2025.201419","DOIUrl":"10.1016/j.humgen.2025.201419","url":null,"abstract":"<div><div>Pediatric acute myeloid leukemia (AML) is a rare but curable hematologic malignancy. This study aims to investigate miR-146a rs2910164 G/C and miR-499 rs3746444 T/C in childhood AML.</div><div>Genotyping and expression analysis were performed in 214 AML pediatric patients in Iran.</div><div>The homozygous mutant genotypes of the miR-146a and miR-499 were related to approximately 2-fold increased risk of pediatric AML occurrence [(OR: 1.97, 95 %CI: 1.090–3.561; <em>p</em> = 0.024); (OR: 2.319; 95 % CI: 1.238–4.346; <em>p</em> = 0.008), respectively]. A significant difference in the frequency of the mutant allele C for miRNA-146a rs2910164 was observed in cases compared to the control group (OR: 1.64, 95 % CI: 1.221–2.207; <em>p</em> = 0.001). The combination of the miR-146a GG and miR-499 CC genotypes was over four times more frequent in AML patients (OR: 4.148; 95 % CI: 1.714–10.040; <em>p</em> = 0.001). MiR-146a and miR-499 expression levels are significantly upregulated in AML patients (2.1-fold and 1.4-fold, respectively); particularly, mutant genotypes of miR-146a and miR-499 showed 3.7-fold and 2.4-fold higher expression (p˂0.05). Based on our bioinformatics analysis data, the mutant allele C exhibited lower stability compared to the wild-type allele G, which may indicate a diminished binding affinity toward target mRNAs and consequently impairment of its regulatory function. Our results revealed that the presence of the mutant alleles is associated with an increased risk of pediatric AML and elevated miRNA expression levels.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201419"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084192","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":"Targeting Hub Genes in Spinocerebellar Ataxia type 2: An Genomics and Molecular Dynamics Approach to Drug Discovery","authors":"Surbhi Singh ,&nbsp;Suchitra Singh ,&nbsp;Deepika Joshi ,&nbsp;C. Mohanty ,&nbsp;Royana Singh","doi":"10.1016/j.humgen.2025.201415","DOIUrl":"10.1016/j.humgen.2025.201415","url":null,"abstract":"<div><div>Spinocerebellar ataxia Type 2 (SCA2) is a progressive brain disorder that impacts movement and coordination, primarily due to genetic mutations. This study employed computational techniques to identify potential treatment targets for SCA2. Gene expression data from GEO datasets (GSE189417, <span><span>GSE151276</span><svg><path></path></svg></span>, <span><span>GSE200530</span><svg><path></path></svg></span>) were analyzed to identify genes that displayed increased activity in SCA2 patients. Genes with a fold change (FC) greater than 1.2 and a <em>p</em>-value of less than 0.05 were chosen. A network of interacting proteins was subsequently constructed using STRING, where key genes, Epidermal Growth Factor Receptor (EGFR) and Interleukin-6 (IL6), were recognized through the CytoHubba plugin in Cytoscape. An additional biological function analysis was conducted using Gene Ontology and KEGG pathway analyses to enhance the understanding of the processes related to SCA2. The structures of these key genes were examined, and their active sites were mapped. A total of 100 natural compounds known for their neuroprotective effects were assessed through molecular docking. Among these, Withaferin A emerged as the most promising candidate, demonstrating strong binding to EGFR (−11.6 kcal/mol) and IL6 (−9.4 kcal/mol). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of Withaferin A were evaluated, confirming its high absorption in the gastrointestinal tract, and non-toxic nature. To further assess its effectiveness and stability, molecular dynamics simulations were conducted for 100 ns, indicating stability. The interactions between Withaferin A and the target proteins (EGFR and IL6) were found to be stable, with minimal structural fluctuations and favorable binding free energy. Based on these findings, it is suggested that Withaferin A may represent a promising therapeutic option for SCA2 by targeting EGFR and IL6. However, further in vivo and in vitro studies are necessary to verify its potential effectiveness for clinical use.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"44 ","pages":"Article 201415"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090338","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}