Ask about this productRelated genes to: TRPM4 antibody
- Gene:
- TRPM4 NIH gene
- Name:
- transient receptor potential cation channel subfamily M member 4
- Previous symbol:
- -
- Synonyms:
- FLJ20041
- Chromosome:
- 19q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-11
- Date modifiied:
- 2016-01-28
Related products to: TRPM4 antibody
Related articles to: TRPM4 antibody
- Neonatal bacterial sepsis (NBS) remains a major global burden. Although immune dysfunction is central to its pathogenesis, the causal contribution of specific immune cell phenotypes and their upstream genetic regulation is unclear. This study aimed to test whether genetically predicted gene expression influences NBS risk through immune cell traits using an integrative two-step Mendelian randomization (MR) mediation framework. We combined eQTLGen whole-blood expression quantitative trait loci (n ≈ 30,000), genome-wide association study of 731 immune traits (Sardinian cohort, n ≈ 3757), and FinnGen R12 NBS summary statistics (P16_BACTERIAL_SEPSIS_NEWBO; 203 cases, 499,933 controls). Instruments met genome-wide significance, stringent linkage disequilibrium clumping, and F-statistic >10. Primary analyses used inverse-variance weighted MR, with MR-Egger and weighted median as sensitivity analyses. Mediation was estimated as the product of effects. Colocalization (coloc; summary-data-based Mendelian randomization-heterogeneity in dependent instruments) was used to evaluate shared causal variants. Heterogeneity (Cochran Q), MR-Egger intercepts, leave-one-out, and reverse MR were performed. We identified 147 gene expressions and 23 immune traits associated with NBS after false discovery rate correction. Two-step MR yielded multiple gene-immune-NBS mediation chains, with CD28-related T-cell phenotypes consistently prominent. The TRPM4 → CD28 on double-negative T cells → NBS pathway showed the largest mediation proportion (~40.54%) and remained directionally consistent across sensitivity tests. Several colocalized signals (e.g., DBF4B, SNCA, SYCE1L) supported shared variants with immune traits; however, not all corresponding mediation paths passed heterogeneity/sensitivity checks, and are therefore interpreted as suggestive rather than definitive. Associations involving CD64 on monocyte subsets were not robust across sensitivity analyses and were not retained as primary findings. Reverse MR did not indicate feedback from NBS liability to the immune traits prioritized in forward analyses. Genetically informed immune phenotypes (particularly CD28-related T-cell features and the broader CD8bright/regulatory T cell axis) appear to partly mediate the effect of gene expression on NBS susceptibility. Colocalized mediation signals provide supportive, hypothesis-generating evidence but require cautious interpretation given sensitivity/heterogeneity findings. These results motivate neonatal-specific validation and functional studies to refine mechanistic targets for risk stratification. - Source: PubMed
Liang JingWei RongYi WeiChen JunchangLi DongxiaoXiao LinLai QiuruFang QiutingLü JibaoWei YingcaiYuan JiaquanGan Junhong - Single-cell RNA sequencing (scRNA-seq) frameworks lack explainable approaches for identifying cell subpopulations harboring strong pairwise monotonic gene-module relationships between a gene of interest (GOI) and its co-expressed genes. In this study, CEP-IP is introduced as a novel explainable machine learning framework to address this gap. - Source: PubMed
Publication date: 2026/04/16
Wong Kah Keng - TRPM4 is a calcium-activated, voltage-modulated, non-selective cation channel expressed in various tissues, including the heart. In 2016, we reported on a large French family with progressive heart block type I carrying the variant TRPM4 p.I376T. In the present study, the aim was to investigate the consequence of the channel variant TRPM4 p.I376T in cardiac physiology in a newly generated Trpm4 knock-in mouse line. Male and female Trpm4 knock-in (Trpm4) and wild-type mice of different young ages (12, 18, 24 and 36 weeks old) were phenotyped using surface ECGs. Western blots were performed to quantify TRPM4 protein surface expression in cardiac tissue. Finally, patch-clamp experiments were conducted to quantify the 'TRPM4 current' from freshly isolated ventricular cardiomyocytes. Assessment of cardiac electrophysiology using surface ECGs indicated no significant differences between the two genotypes at any age. Western blot analyses revealed a significant decrease in the highly glycosylated fraction of the TRPM4 protein in Trpm4 hearts compared with wild-type tissues. However, this alteration did not influence the 'TRPM4 current' when comparing Trpm4 and wild-type cardiomyocytes. These results indicate that the TRPM4 variant, TRPM4 p.I376T, does not alter electrical activity in the murine heart at young ages but decreases the amount of highly glycosylated TRPM4 protein expressed in the heart via an unknown mechanism. - Source: PubMed
Publication date: 2026/04/29
Guichard Sabrinadi Lorenzo EmanueleSchneiter DominicEssers MariaArullampalam PrakashRougier Jean-SébastienAbriel Hugues - Bladder cancer (BLCA) is a common malignancy of the urinary system, yet the therapeutic relevance of transient receptor potential cation channel subfamily M member 4 (TRPM4) remains unclear. By integrating single-cell and whole-genome transcriptomic data, this study revealed significant transient receptor potential cation channel subfamily M member 4 (TRPM4) overexpression in bladder cancer (BLCA) ( < 0.05), particularly in epithelial cells. Intersection analysis identified 220 candidate genes (7,808 DEGs1, 4,683 DEGs2, and 4,802 key cell module genes). A risk model was constructed comprising six screened prognostic marker genes, namely, protein unc-93 homolog B1 (UNC93B1), family with sequence similarity 193 member B (FAM193B), protein O-glucosyltransferase (POGLUT3), fibrillin-1 (FBN1), microtubule-associated protein 1B (MAP1B), and RUNX family transcription factor 2 (RUNX2). The model demonstrated marked differences among the risk groups. Gene set enrichment analysis revealed significant disparities in key pathways, including the melanoma pathway ( < 0.05). Furthermore, immune infiltration analysis has identified 12 distinct immune cell types, including naive B cells, which showed a < 0.05 distribution. The observed distribution was uneven. In the drug sensitivity analysis, 112 drugs (including WZ3105; < 0.05) showed differential responses, and UNC93B1 showed high positive expression in BLCA tissues (positive cell proportion > 75%). Our studies confirmed that TRPM4 has significant prognostic value and is a potential novel diagnostic and therapeutic target for BLCA. - Source: PubMed
Publication date: 2026/04/13
Zhao QiQin ZitongLiu RunzhangZuo KangweiGuo ChenghaoJing SuoshiLi Weiping - Large-scale clinical genome sequencing yields vast numbers of variants of unknown significance (VUSs). The high frequency of VUSs and the paucity of platforms to characterize their functional impact pose significant challenges for clinical decision making. Here, we present an integrated end-to-end platform, REVi-SCOPE (Rapid evaluation of variants in single cells by optogenetics and prime editing), for characterization of the impact of VUSs on cardiac physiology. Our strategy consists of (1) introduction of variants directly into wild-type (WT) human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) via prime editing; (2) optogenetic assessment of calcium and membrane voltage dynamics in single hiPSC-CMs within the pool of edited and unedited cells; and (3) in situ single-cell genotyping of the phenotyped hiPSC-CMs with single-allele resolution. By optimizing and integrating each of these steps, we created a platform that enables VUS characterization in 10 days. We validated the REVi-SCOPE's capabilities by analyzing the properties of established arrhythmogenic variants. We then used REVi-SCOPE to reveal the functional impact of a VUS, , identified in a child with a conduction block. Together, our results show that REVi-SCOPE enables functional characterization of VUSs linked to cardiac arrhythmias with unprecedented throughput. - Source: PubMed
Publication date: 2026/04/19
Wang Xiao-TingChen Po-TaMayourian JoshuaRipple LeonaTharani YashasviShang TiantianPavlaki NikoletaShani KevinJang YongjunJanson Christopher MMah DouglasParker Kevin KPu William THa TaekjipBezzerides Vassilios J