Human Gene最新文献

{"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":"2025-10-03","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}

{"title":"A review on the role of miR-576 in human disorders","authors":"Alireza Soleimani ,&nbsp;Mohsen Ahmadi ,&nbsp;Mahla Sanati ,&nbsp;Hadi Adabi ,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.humgen.2025.201491","DOIUrl":"10.1016/j.humgen.2025.201491","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) have pivotal role in post-transcriptional gene regulation by binding to target mRNAs, resulting in their degradation or translational repression. They contribute to the pathogenesis of several disorders, including cancer, autoimmune conditions and metabolic disorders. Among these non-coding transcripts is miR-576, a miRNA with dual roles in tumorigenesis and significant participation in non-malignant conditions. Through modulation of key cellular processes such as proliferation, apoptosis, migration, and immune responses, this miRNA participates in the pathoetiology of a variety of human disorders. This manuscript aims to comprehensively review the current understanding of miR-576 in malignant and non-malignant disorders, emphasizing its mechanistic roles, clinical implications, and therapeutic potential. By integrating the current knowledge on its role, we offer insights into the dual nature of miR-576 in disease pathogenesis and discover future directions for research and therapeutic development.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201491"},"PeriodicalIF":0.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219617","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":"Integrated in silico and experimental analysis identifies MAGE-A3, TRIM28, and HLA-A as immunomodulatory targets in lung cancer","authors":"Gaurang Telang ,&nbsp;Smriti Mishra ,&nbsp;Anurag Sureshbabu ,&nbsp;Sagar Barage ,&nbsp;A.W. Santhosh Kumar ,&nbsp;Rajshri Singh","doi":"10.1016/j.humgen.2025.201492","DOIUrl":"10.1016/j.humgen.2025.201492","url":null,"abstract":"<div><div>MAGEA3, a cancer-testis antigen selectively expressed in tumors, has been widely explored as a target for cancer immunotherapy, yet its broader immunoregulatory function in the lung tumor microenvironment remains insufficiently characterized. In this study, we conducted an integrative in silico analysis using transcriptomic data from TCGA-LUSC to delineate the expression landscape, immune contexture, and molecular interactions of MAGEA3. Protein–protein interaction networks constructed via STRING and ranked through CytoHubba identified TRIM28 and HLA-A as key co-regulatory molecules, implicating MAGEA3 in transcriptional repression and antigen presentation. TIMER2.0 deconvolution revealed cell-type–specific associations, including differential relationships with CD8⁺ T cells, dendritic cells, and macrophages. Gene-wise survival modeling in TCGA-LUSC indicated MAGEA3 and MAGEA6 associate with reduced overall survival, whereas TRIM28 showed a borderline protective trend. Experimental validation via RT-qPCR in A549 cells confirmed detectable expression of MAGEA3, TRIM28, and HLA-A, reinforcing the computational predictions and highlighting potential cross-histological relevance. Collectively, these findings position MAGEA3 within immunomodulatory circuits of lung cancer and support its consideration in multimodal immunotherapeutic paradigms.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201492"},"PeriodicalIF":0.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219618","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":"2025-09-29","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":"The LEPR gene: A multifaceted regulator of energy homeostasis, obesity pathogenesis, and metabolic health","authors":"Isar Sharma ,&nbsp;Nishutosh ,&nbsp;Kritika Bakshi ,&nbsp;Ritu Mahajan ,&nbsp;Nisha Kapoor","doi":"10.1016/j.humgen.2025.201486","DOIUrl":"10.1016/j.humgen.2025.201486","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>This review examines the leptin-LEPR axis and its role in regulating energy balance and obesity. The <em>LEPR</em> gene provides the essential instructions for synthesizing the leptin receptor, a protein of paramount importance within the neuroendocrine system that orchestrates energy balance. Leptin, an adipokine secreted primarily by adipose tissue, functions as a critical signal reflecting the body's energy stores. It modulates appetite and energy expenditure by binding to its cognate receptor, which is predominantly expressed in the hypothalamus.</div></div><div><h3>Materials &amp; methods</h3><div>The authors comprehensively examined a wide range of studies to detail the function of the <em>LEPR</em> gene and the complex intracellular signalling pathways it initiates. The focus was on understanding how dysfunctions, from rare genetic mutations to common acquired leptin resistance, disrupt these homeostatic mechanisms.</div></div><div><h3>Results</h3><div>The review confirms that when leptin binds to its receptor, it initiates a complex cascade of intracellular signalling pathways. These include the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/Akt pathways. Dysfunction of the leptin-LEPR axis, whether stemming from rare genetic mutations leading to congenital leptin receptor deficiency or the more prevalent acquired leptin resistance observed in common obesity, severely disrupts these intricate homeostatic mechanisms. Such disruptions invariably manifest as profound hyperphagia (excessive hunger) and severe obesity.</div></div><div><h3>Conclusion</h3><div>A comprehensive understanding of the <em>LEPR</em> axis and its intricate signalling networks is therefore fundamental for elucidating the pathophysiology of obesity and for the development of effective therapeutic strategies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201486"},"PeriodicalIF":0.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157766","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":"Crosstalk between MitomiRs and cardiovascular disease","authors":"Rashi Khare,&nbsp;Nilanjana Ghosh,&nbsp;Sunanda Arya,&nbsp;Swati Srivastava,&nbsp;Iti Garg","doi":"10.1016/j.humgen.2025.201488","DOIUrl":"10.1016/j.humgen.2025.201488","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial microRNAs (mitomiRs) have emerged as vital regulators in the etiology of cardiovascular disease (CVD). Differential mitomiR expression contributes to mitochondrial dysfunction which is a key contributor to heart failure, ischemia, and cardiomyopathic hypertrophy. Despite advances, the specific downstream pathways and molecular mechanisms influenced by mitomiRs remain inadequately defined. We have investigated mitomiRs which are associated with CVD.</div></div><div><h3>Methods</h3><div>A systematic literature review was conducted using PubMed to identify mitomiRs associated with cardiovascular disease. Experimentally validated target gene interactions were analyzed using MiRDB and MirTarBase. Protein-protein interaction (PPI) networks were constructed with STRING, and functional enrichment analyses, including Gene Ontology (GO) and KEGG pathway analyses, were performed using an SR plot. Hub gene identification was executed via the CytoHubba plugin in Cytoscape, pinpointing key regulatory nodes within the network.</div></div><div><h3>Results</h3><div>The present study identified 21 mitomiRs that modulate the coagulation gene pathway in cardiovascular disease. Notably, the amyloid precursor protein (APP) was recognized as a central hub. APP acts as a crucial intersection between the regulation of coagulation and mitochondrial protein clusters. Among the top 15 hub genes, APP was highlighted as a significant molecular regulator that potentially linked mitochondrial dysfunction with cardiovascular pathology.</div></div><div><h3>Conclusion</h3><div>Mitomir plays a critical role in the regulation of mitochondrial function in various cardiovascular diseases. Mitomir not only regulates the mitochondrial function but also are involved in the coagulation pathway. Mitochondrial dysfunction may have been a result of the involvement of amyloid precursor protein which itself is the main regulator of Alzheimer's disease. Hence uncovering the potential role behind APP in cardiovascular disease may help to unlock a potential target that is still missing in CVD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201488"},"PeriodicalIF":0.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265457","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 role of TBXA2R, TGF-β1 and Il-18 gene polymorphisms in the pathogenesis of pollen induced allergic asthma- a case-control study from West Bengal, India","authors":"Priti Mondal ,&nbsp;Indranil Ganai ,&nbsp;Himani Biswas ,&nbsp;Saibal Moitra ,&nbsp;Sanjoy Podder","doi":"10.1016/j.humgen.2025.201485","DOIUrl":"10.1016/j.humgen.2025.201485","url":null,"abstract":"<div><h3>Background</h3><div>Allergic asthma is a chronic inflammatory disease of the respiratory system's conducting airways affecting 330 million people globally and causes intermittent attacks of breathlessness, wheezing, airway hyper-reactivity and coughing when exposed to specific allergens. Thromboxane A2 receptor (TBXA2R), Transforming Growth Factor Beta 1 (TGF-β1) and Interleukin-18 (IL-18) genes are reported to be involved in inflammatory and immune response pathways related to asthma. Based on the above facts it can be hypothesized that single nucleotide polymorphisms (SNPs) in these genes may be associated with the asthma phenotype.</div></div><div><h3>Objectives</h3><div>The present study aims to analyze the role of the TBXA2R rs4523, TGF-β1 rs1800470, IL-18 rs1946519, IL-18 rs1946518 and IL-18 rs549908 gene polymorphism in asthma susceptibility among the population of West Bengal, India.</div></div><div><h3>Results</h3><div>Maximum number of patients showed sensitivity towards <em>Azadirachta indica</em> (73.46 %), followed by <em>Cocos nucifera</em> (72.27 %), <em>Caesalpinia pulcherrima</em> (65.17 %), etc. Significant difference in genotype and allele frequencies was obtained between the study groups for TBXA2R rs4523 and IL-18 rs1946519 polymorphisms. Asthma patients possessed significantly higher frequency of TBXA2R rs4523 CC and IL-18 rs1946519 TT genotypes than controls. TBXA2R rs4523 CC and IL-18 rs1946519 TT genotype bearing patients showed highest intensity of SPT reactions. Patients bearing rs4523 CC and rs1946519 TT genotypes had significantly higher FEV1/FVC ratio, total IgE level and blood Eosinophil count than heterozygous or major genotype bearers.</div></div><div><h3>Conclusion</h3><div>The present study concluded that TBXA2R rs4523 and IL-18 rs1946519 polymorphisms are associated with allergic asthma susceptibility in the population of West Bengal, India.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201485"},"PeriodicalIF":0.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157765","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":"2025-09-22","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":"Evaluation of the frequency of Dectin-1 rs3901533 A > C and rs7309123 G > C gene variants in patients with acute myeloid leukemia (AML): A case-control study","authors":"Davood Alinezhad Dezfuli ,&nbsp;Ehsan Sarbazjoda ,&nbsp;Nasrin Amirrajab ,&nbsp;Tina Vosoughi ,&nbsp;Alireza Momeni ,&nbsp;Mohammad Ali Jalali Far","doi":"10.1016/j.humgen.2025.201482","DOIUrl":"10.1016/j.humgen.2025.201482","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) is a serious blood cancer mainly affecting adults, and its predisposing genetic factors remain unclear. While recent studies have linked dectin-1 polymorphisms to fungal infection risk in AML, their relationship with AML susceptibility has not been studied. This study evaluates the association between two dectin-1 single-nucleotide polymorphisms (SNPs) of rs3901533 A &gt; C and rs7309123 G &gt; C and AML risk.</div></div><div><h3>Methods &amp; materials</h3><div>A total of 103 participants (53 AML patients and 50 age- and sex-matched healthy controls) from the Iranian population were included in this study. Both of the polymorphisms were genotyped using the tetra-ARMS-PCR method.</div></div><div><h3>Results</h3><div>The genotype distributions of rs3901533 A &gt; C and rs7309123 G &gt; C polymorphisms did not differ significantly between AML patients and controls under additive, dominant, or recessive genetic models (<em>p-value</em> &gt; 0.05). Furthermore, allele frequencies for both SNPs showed no significant association with AML risk (<em>p-value</em> &gt; 0.05). None of the genotypes or alleles increased the risk of AML (<em>p-value</em> &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Neither the rs3901533 A &gt; C nor the rs7309123 G &gt; C polymorphisms are contributors to increased susceptibility to AML. However, further investigations are needed.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201482"},"PeriodicalIF":0.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265696","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":"Early-onset nephrolithiasis and persistent microscopic hematuria in a child with a novel pathogenic COL4A5 variant in Alport syndrome: A case report and literature review","authors":"Firoz Ahmad ,&nbsp;Niladri Bose ,&nbsp;Alec Correa ,&nbsp;Sapna Sandal ,&nbsp;Mukesh Kumar ,&nbsp;Akashi Vyas ,&nbsp;Amisha Shah ,&nbsp;Meenu Angi ,&nbsp;Jigar Suthar ,&nbsp;Pooja Chaudhary ,&nbsp;Anindyajit Banerjee ,&nbsp;Spandan Chaudhary ,&nbsp;Neeraj Arora","doi":"10.1016/j.humgen.2025.201483","DOIUrl":"10.1016/j.humgen.2025.201483","url":null,"abstract":"<div><div>A 4-year-old male with persistent microscopic hematuria, hypocalciuria along with hypocitraturia. Renal ultrasound revealed bilateral microcalculi without structural anomalies. Ophthalmic and auditory evaluations were unremarkable. Family history indicated renal disease in the maternal aunt and maternal microscopic hematuria. Whole-exome sequencing (WES) identified a novel hemizygous nonsense variant in <em>COL4A5</em> (NM_033380.3: c.1555C &gt; T; p.Gln519*), truncating the protein at codon 519 of 1770. The variant, inherited from the mildly symptomatic mother (microscopic hematuria, right renal cyst), was absent in population databases and classified as pathogenic based on ACMG criteria (PVS1_Strong, PM2_Supporting, PP1_Supporting, PP4_Supporting). CytoScan 750 K array ruled out copy-number variations. This case expands the genotypic spectrum of Alport syndrome (AS), demonstrating an early presentation with nephrolithiasis, and underscores the diagnostic utility of WES in atypical inherited nephropathies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201483"},"PeriodicalIF":0.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157764","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}