Human Gene最新文献

{"title":"Association of DVWA (rs7639618) gene polymorphisms with knee osteoarthritis susceptibility: An updated systematic review and meta-analysis","authors":"Annamalai R ,&nbsp;Venkatramanaiah C ,&nbsp;Marimuthu Raja ,&nbsp;Santhosh Kumar Yasam ,&nbsp;Sujhithra A ,&nbsp;Catherine Rexy ,&nbsp;Vignesh Narasimman ,&nbsp;D. Danis Vijay","doi":"10.1016/j.humgen.2025.201519","DOIUrl":"10.1016/j.humgen.2025.201519","url":null,"abstract":"<div><h3>Background &amp; aim</h3><div>Knee osteoarthritis (KOA)<span><span>¹</span></span> is a common degenerative joint disease characterized by progressive cartilage breakdown that leads to pain and reduced mobility. Although genetic predisposition including the double von Willebrand factor A (DVWA; rs7639618) gene polymorphism has been implicated in KOA, previous case–control studies have reported inconsistent findings. This updated meta-analysis aims to clarify the association between the DVWA (rs7639618) gene polymorphism and KOA susceptibility.</div></div><div><h3>Materials &amp; methods</h3><div>A systematic search was performed in Pub Med, Web of Science, Science Direct, and Google Scholar for case–control studies published up to June 2025. Eligible studies reported genotype and allele distributions for rs7639618 in KOA cases and controls. Study quality was assessed using the Newcastle–Ottawa Scale (NOS).<span><span>²</span></span> Odds ratios (ORs)<span><span>³</span></span> with 95 % confidence intervals (CIs)<span><span>⁴</span></span> were calculated under allele, recessive, dominant, and over-dominant models. Heterogeneity was evaluated using the Q test and I² statistic, and random- or fixed-effects models were applied accordingly. Subgroup analyses were conducted by ethnicity, and publication bias was assessed with funnel plots and Egger's test. Sensitivity analysis was carried out by excluding each study.</div></div><div><h3>Results</h3><div>Thirteen studies comprising 7110 KOA cases and 6931 controls were included. Pooled analyses across all genetic models showed no statistically significant association between rs7639618 and KOA susceptibility. For the allele contrast model, the overall OR was 1.03 (95 % CI: 0.90–1.19); for the recessive model, OR was 1.06 (95 % CI: 0.90–1.25); for the dominant model, OR was 1.08 (95 % CI: 0.85–1.38); and for the over-dominant model, OR was 0.98 (95 % CI: 0.91–1.05). Subgroup analyses revealed no increased risk in either Asian or Caucasian populations. Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected.</div></div><div><h3>Conclusion</h3><div>The findings of this meta-analysis suggest that the DVWA (rs7639618) polymorphism is not significantly associated with KOA susceptibility in the overall population or within specific ethnic groups. Despite the rigorous methodology and comprehensive analysis, the presence of substantial heterogeneity in some genetic models underscores the need for further well-designed, large-scale studies across diverse populations.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201519"},"PeriodicalIF":0.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681724","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":"Comprehensive in silico and in vitro studies reveal the miR-30a/CALU axis as a potential therapeutic target in colorectal cancer","authors":"Parinaz Nasri Nasrabadi ,&nbsp;Forouzandeh Mahjoubi ,&nbsp;Gilles A. Robichaud ,&nbsp;Fatemeh Masoumi ,&nbsp;Alireza Zomorodipour","doi":"10.1016/j.humgen.2025.201518","DOIUrl":"10.1016/j.humgen.2025.201518","url":null,"abstract":"<div><div>Colorectal cancer (CRC) progression involves complex molecular mechanisms that remain incompletely understood. This study investigated the expression and functional significance of calumenin (CALU) in CRC pathogenesis. Bioinformatic analyses revealed significant CALU upregulation in CRC compared to normal tissues, with expression increasing progressively from primary to metastatic tumors. Protein-protein interaction networks positioned CALU as a hub gene interacting with multiple cancer-associated proteins. Single-cell RNA sequencing revealed cell-type-specific CALU expression patterns, with the highest levels observed in tumor-derived colonic goblet cells, colonocytes, and fibroblasts. MicroRNA target prediction algorithms identified miR-30a as a potential CALU regulator, which we confirmed through luciferase reporter assays. In CRC tissues and cell lines, miR-30a expression was significantly downregulated and inversely correlated with CALU levels. Functionally, restoration of miR-30a expression in CRC cells suppressed CALU expression, inhibited proliferation, induced G0/G1 cell cycle arrest, promoted apoptosis, and reduced migration and invasion capabilities. These effects were rescued by CALU overexpression, confirming CALU as a functional target of miR-30a. Analysis of 50 paired clinical specimens supported these findings, with CALU upregulation and miR-30a downregulation correlating with poor differentiation and lymph node metastasis. Our findings introduce the miR-30a/CALU axis as a potential therapeutic target in CRC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201518"},"PeriodicalIF":0.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616456","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":"Vitamin D receptor gene polymorphisms and the risk of autism spectrum disorder (ASD): A meta-analysis","authors":"Ghasem Fakourizad ,&nbsp;Alireza Hatami ,&nbsp;Saeed Aslani ,&nbsp;Mohammad Masoud Eslami ,&nbsp;Danyal Imani ,&nbsp;Bahman Razi ,&nbsp;Tannaz Jamialahmadi ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.humgen.2025.201517","DOIUrl":"10.1016/j.humgen.2025.201517","url":null,"abstract":"<div><div>Several investigations have noted to the potential link between <em>Vitamin D Receptor</em> (<em>VDR</em>) gene polymorphisms and autism spectrum disorder (ASD); however, the findings have been controversial. To find a convincing answer, we performed this meta-analysis to identify a reliable understanding for plausible association of <em>VDR</em> gene SNPs and risk of ASD susceptibility. A systematic search was performed to search for relevant studies assessing the association between the Cdx (rs11568820), TaqI (rs731236), <em>Fok</em>I (rs2228570), <em>Apa</em>I (rs7975232), and <em>Bsm</em>I (rs1544410) SNPs of the <em>VDR</em> gene and susceptibility to ASD released before January 2024. Odd Ratio (OR) and 95 % CI were used to show statistical relationship between the <em>VDR</em> gene SNPs and ASD. In the final analysis 14 studies containing 2023 ASD patients and 2008 healthy individuals were included. The comprehensive analysis revealed that the TaqI variant across all genotypes, and the <em>Fok</em>I variant in recessive, allelic, and homozygote genetic models, were associated with an increased risk of ASD. According to the findings of this meta-analysis, TaqI and FokI SNPs play a role in predisposition to ASD; however, because of limitation in sample size and geographical distribution of included studies, findings should be interpreted cautiously.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201517"},"PeriodicalIF":0.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616455","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":"Low GOPC mRNA expression is a novel candidate associated with increased risk of acute myeloid leukemia","authors":"Taisir A. Kadhim ,&nbsp;Randa R. Ghamyes ,&nbsp;Dhay A. Azeez ,&nbsp;Mustafa A. Bashi ,&nbsp;Ali A. Alsodani ,&nbsp;Mohammed K. Al-Qayyim ,&nbsp;Noor T. Kadhim ,&nbsp;Rawan A. Nijeeb ,&nbsp;Dhuha F.N. Bani-Wais ,&nbsp;Ali H. Ad'hiah","doi":"10.1016/j.humgen.2025.201516","DOIUrl":"10.1016/j.humgen.2025.201516","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a genetically heterogeneous malignant hematopoietic disorder, and research continues to update its genetic drivers. Golgi-associated PDZ and coiled-coil motif-containing (GOPC) is a signaling protein implicated in regulating cellular trafficking of transmembrane proteins. Recent research has shown that the gene encoding GOPC exhibits dysregulated expression in colorectal cancer. In AML, the significance of <em>GOPC</em> expression in disease risk and pathogenesis has not been explored. Therefore, a case-control study was conducted to evaluate <em>GOPC</em> mRNA expression in a cohort of 100 AML patients and 100 controls. <em>GOPC</em> expression was quantified using a reverse transcription-quantitative PCR-based fold change method (2^–ΔCt). Statistical data management included receiver-operating characteristic (ROC) curve analysis, disease-risk assessment, and assessment of correlation with AML characteristics. Results revealed that <em>GOPC</em> expression levels (median [interquartile range: 25–75 %]) were significantly decreased in patients compared to controls (0.04 [0.02–0.14] vs. 0.73 [0.18–1.16]; probability &lt;0.001). ROC curve analysis demonstrated the reliability of <em>GOPC</em> expression in distinguishing between AML patients and controls (area under the curve = 0.91; probability &lt;0.001). Disease-risk assessment indicated that low <em>GOPC</em> expression was linked to a 16.15-fold increased risk of AML. <em>GOPC</em> expression was not affected by clinical and genetic characteristics of AML or chemotherapy and was not correlated with diagnostic laboratory criteria<em>.</em> In conclusion, <em>GOPC</em> mRNA expression was down-regulated in AML and was not affected by the patient's clinical, genetic, or laboratory characteristics. Low <em>GOPC</em> expression may be considered a potential risk factor for AML.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201516"},"PeriodicalIF":0.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616454","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":"Multi-dataset transcriptomic study reveals key regulatory pathways and drug targets in rheumatoid arthritis","authors":"Ali Babaei-Ghaghelestany ,&nbsp;Somayeh Pashaei ,&nbsp;Reza Khodarahmi ,&nbsp;Maryam Mehrabi ,&nbsp;Masomeh Mehrabi","doi":"10.1016/j.humgen.2025.201515","DOIUrl":"10.1016/j.humgen.2025.201515","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, progressive joint destruction, and systemic complications. Despite significant advancements in RA research, the molecular mechanisms driving disease progression remain incompletely understood. This study employed an integrated bioinformatics approach to uncover differentially expressed genes (DEGs), key signaling pathways, and potential therapeutic targets in RA. Four publicly available microarray datasets (GSE56649, GSE93272, GSE110169, and GSE45291) from the NCBI Gene Expression Omnibus (GEO) were analyzed using the <em>limma</em> package in R with thresholds of |log2 fold change| &gt; 0.1 and adjusted <em>p</em>-value &lt;0.05. Common DEGs across datasets were identified by Venn diagram analysis and subjected to functional enrichment. Protein–protein interaction (PPI) networks were constructed using STRING and analyzed in Cytoscape with CytoHubba to extract hub genes. Clustering was performed with Gephi, and drug–gene interactions were explored using DGIdb. A total of 394 common DEGs were identified, significantly enriched in proteasome function, chromatin remodeling, oxidative phosphorylation, JAK-STAT signaling, and Th17 cell differentiation—pathways central to RA pathogenesis. Network analysis revealed ten hub genes (<em>PSMA4</em>, <em>HSP90AA1</em>, <em>PSMD2</em>, <em>TRIM28</em>, <em>RBBP4</em>, <em>SIRT1</em>, <em>RPL35</em>, <em>HNRNPK</em>, <em>MAPK8</em>, and <em>PSMD10</em>) as potential regulators in RA, implicated in inflammation, immune signaling, oxidative stress, and cartilage degradation. Among them, <em>HSP90AA1</em>, <em>SIRT1</em>, and <em>MAPK8</em> showed particular relevance to RA through modulation of NF-κB, STAT3, and MAPK pathways. Drug–gene interaction analysis identified 21 small molecules targeting these hub genes, highlighting opportunities for drug repurposing. Collectively, these findings provide new insights into RA pathogenesis and highlight candidate biomarkers and therapeutic targets that may support earlier diagnosis and the development of novel targeted therapies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201515"},"PeriodicalIF":0.7,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616458","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":"Response to commentary on Livni & Skorecki, “Distinguishing between founder and host population mtDNA lineages in the Ashkenazi population”","authors":"Joseph Livni ,&nbsp;Karl Skorecki","doi":"10.1016/j.humgen.2025.201514","DOIUrl":"10.1016/j.humgen.2025.201514","url":null,"abstract":"<div><div>This document is a response to Joseph Fiaith, Commentary on Livni &amp; Skorecki, “Distinguishing between Founder and Host Population mtDNA Lineages in the Ashkenazi Population”. Human Gene 46. doi: 10.1016.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201514"},"PeriodicalIF":0.7,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681725","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":"Upregulation of long non-coding RNA LINC01614 in breast cancer and its association with clinicopathological features","authors":"Mohammad Reza Forouzesh Kia ,&nbsp;Hajar Yaghoobi ,&nbsp;Nooshafarin Shirani ,&nbsp;Reza Eshraghi Samani","doi":"10.1016/j.humgen.2025.201501","DOIUrl":"10.1016/j.humgen.2025.201501","url":null,"abstract":"<div><div>Epigenetic factors, such as regulatory RNAs, are among the most important drivers of breast cancer. Many of these non-coding RNAs are long non-coding RNAs (lncRNAs). Research has shown that numerous lncRNAs play a significant role in the development of breast cancer and can be categorized as either oncogenic or tumor suppressor. This study aims to identify the candidate lncRNAs relevant to breast cancer through bioinformatics studies and then investigate changes in their expression levels, specifically focusing on LINC01614 lncRNAs, in cancerous tissues in comparison to adjacent noncancerous tissues.</div></div><div><h3>Method</h3><div>In this study, gene expression data for 12,727 long non-coding RNAs (lncRNAs) were analyzed, consisting of 837 breast cancer samples and 105 normal samples, using the TANRIC database. To explore the potential biological functions of selective lncRNA, we identified its top 50 co-expressed genes using the lncHUB platform. This list of genes was subsequently subjected to comprehensive enrichment analysis, using the Enrichment Analysis Visualizer Appyter. Post-surgery patient samples were collected, and RNA was isolated and converted to cDNA for real-time quantitative PCR (RT-qPCR) to evaluate gene expression levels. Graph Pad Prism was employed for statistical evaluation of the data.</div></div><div><h3>Result and discussion</h3><div>Differential expression analysis revealed 64 lncRNAs, with LINC01614 showing the highest up-regulation (logFC of 2.34). Functional enrichment analysis of co-expressed genes revealed strong associations with key oncogenic pathways, including extracellular matrix organization, PI3K-AKT-mTOR signaling, and immune response processes. The analysis of long non-coding RNA LINC01614 indicated a significant 6.5-fold increase in cancer samples compared to normal tissues, suggesting its role in breast cancer development. Expression levels varied by tumor grade, with higher levels observed in grades 1 and 2 compared to grade 3, indicating its potential significance in tumor development. The study also explored the relationship between LINC01614 expression and PR-receptor status.</div></div><div><h3>Conclusion</h3><div>This study reveals the multifunctional role of LINC01614 in breast cancer pathogenesis. Its significant overexpression and involvement in diverse oncogenic processes highlight its potential as both a novel diagnostic biomarker and a promising therapeutic target. Further investigations are warranted to elucidate its precise mechanisms and clinical applicability.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201501"},"PeriodicalIF":0.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681726","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":"Computational analysis of missense variants in MT-ND1 and MT-CO2 associated with breast cancer: A functional and structural impact","authors":"Rhuthuparna Malayil ,&nbsp;Anjana Munshi ,&nbsp;Sandeep Singh","doi":"10.1016/j.humgen.2025.201513","DOIUrl":"10.1016/j.humgen.2025.201513","url":null,"abstract":"<div><div>This study explores the impact of genetic variations in two mitochondrial genes, MT-ND1 and MT-CO2 on breast cancer development. Through sequence- and structure-based bioinformatics analysis, an mt.7830 G &gt; A (CGC &gt; CAC) mutation in the MT-CO2 gene was identified in a 60-year-old woman as the most deleterious. This mutation leads to the substitution of a conserved arginine (R82) with histidine, potentially disrupting COX2 function. Publicly available databases highlight that arginine is the most frequently mutated amino acid in human cancers, with codons CGC, CGG, and CGT being the primary sites of substitution. The mt.7830 G &gt; A mutation impairs oxidative phosphorylation (OXPHOS), potentially increasing reactive oxygen species (ROS) production and contributing to disease progression. Additionally, a potential genotoxic influence of arsenic on mitochondrial function cannot be excluded. The variant rs878897170 was identified in a single case. The results are best viewed as preliminary observations and confirmation in larger cohorts and experimental validation are essential to authenticate the findings of the current study.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201513"},"PeriodicalIF":0.7,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571143","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":"Study of the association between MAO-B and 5-HTTLPR polymorphism involved in serotonergic system with unsafe behaviors and personality traits","authors":"Zahra Alizadeh ,&nbsp;Forough Shams ,&nbsp;Vafa Feyzi ,&nbsp;Ali Alboghobeish ,&nbsp;Mostafa Pouyakian","doi":"10.1016/j.humgen.2025.201511","DOIUrl":"10.1016/j.humgen.2025.201511","url":null,"abstract":"<div><h3>Background</h3><div>Unsafe behaviors are believed to be related to genetic differences of people. The present study aimed to the relationship between unsafe behaviors and personality traits with the polymorphism of the genes involved in serotonergic system.</div></div><div><h3>Methods</h3><div>Safety behavior sampling technique, the short form of NEO-five factor inventory (NEO-FFI) and demographic information questionnaire were respectively used. Blood samples were collected for genotyping of the serotonin transporter gene <em>5-HTTLPR</em> and <em>MAO-B</em> polymorphisms.</div></div><div><h3>Result</h3><div>Participants getting high scores in neuroticism and low scores in agreeableness and those possessing 5-<em>HTTLPR</em> SS and LL genotypes, as well as the X_AY genotype of <em>MAO-B</em> A644G polymorphism, were more involved in unsafe behaviors. There was a significant association between <em>5-HTTLPR</em> polymorphism in serotonin transporter of LS and SS genotype and MAO-B polymorphism in <em>MAO-B</em> A644G gene of X_GY genotype is higher compared to the other unsafe behaviors. However, those with 5-<em>HTTLPR</em> LS genotype, as well as the X_GY genotype of <em>MAO-B</em> A644G polymorphism, achieved a great score regarding agreeableness.</div></div><div><h3>Conclusion</h3><div>Due to the role of hereditary differences in individuals' tendency to unsafe behaviors, the results of the present study can be considered in job design wherever the ethics code allows.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201511"},"PeriodicalIF":0.7,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532402","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":"Role of the translocon-associated protein (TRAP)/signal sequence receptor (SSR) complex in the pathogenesis of human diseases","authors":"Darshika Amarakoon,&nbsp;Seong-Ho Lee","doi":"10.1016/j.humgen.2025.201510","DOIUrl":"10.1016/j.humgen.2025.201510","url":null,"abstract":"<div><div>The translocon-associated protein/signal sequence receptor (TRAP/SSR) complex, an integral membrane protein complex of the endoplasmic reticulum (ER), has emerged as a critical regulator of co-translational protein translocation, protein secretion, and cellular homeostasis. Despite its fundamental role, research on the TRAP/SSR complex in human diseases remains limited, focusing mainly on its involvement in cancer, diabetes, neurodegenerative and spinal disorders, and hepatitis B virus infection. This review summarizes recent advances in understanding TRAP/SSR function in disease pathogenesis, highlighting its pro-tumorigenic activity, regulation of insulin biosynthesis and secretion, and potential as a biomarker for early diagnosis of neurodegenerative and spine-related disorders. Furthermore, the TRAP/SSR complex facilitates the translocation and secretion of the hepatitis B e antigen, emphasizing its role in viral pathogenesis. However, substantial research gaps persist due to the novelty of this field, and the molecular mechanisms underlying TRAP/SSR-mediated disease regulation remain incompletely understood. Therefore, future investigations should aim to elucidate the mechanistic links between TRAP/SSR dysfunction and diverse pathological conditions, including metabolic, neurodegenerative, infectious, and malignant diseases. Defining disease-specific downstream effectors and interactions with ER stress pathways – particularly the unfolded protein response and ER-associated degradation – will be critical to clarifying its contribution to cellular homeostasis and disease progression. The development of targeted therapeutic strategies to modulate TRAP/SSR activity, supported by integrative multi-omics and structural biology approaches, may ultimately enable the translation of these insights into diagnostic and therapeutic applications.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201510"},"PeriodicalIF":0.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519418","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}