Ask about this productRelated genes to: TXNDC15 Blocking Peptide
- Gene:
- TXNDC15 NIH gene
- Name:
- thioredoxin domain containing 15
- Previous symbol:
- C5orf14
- Synonyms:
- 2310047H23Rik, FLJ22625
- Chromosome:
- 5q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-04-27
- Date modifiied:
- 2016-12-12
Related products to: TXNDC15 Blocking Peptide
Related articles to: TXNDC15 Blocking Peptide
- Biological systems face a constantly changing environment and must swiftly respond to stimuli, yet how cells sense and adapt to environmental and physiological cues is incompletely understood. Short-lived proteins can be rapidly induced upon perturbation, enabling swift activation of adaptive cellular responses. Leveraging genome-wide data on protein-transcript correlation, we systematically searched for rapid proteolysis substrates whose abundance reflects the activity of the underlying proteolytic machinery. Here, focusing on the candidate substrate ABHD2, we employed CRISPR-based functional screens to dissect its degradation and identified as an essential factor in MARCHF6-mediated ER-associated protein degradation (ERAD). Unexpectedly, TXNDC15 supports substrate exit and degradation from the ER via a catalysis-independent mechanism. Loss of remodels the ER proteome and lipid homeostasis. Together, our work defines a missing component of ERAD and provides a generalizable strategy to decode post-translational regulatory circuits. - Source: PubMed
Publication date: 2026/04/02
Liu YuyangYaochai Michelle YinfeiLiu ShanshanAlwaseem HananBirsoy Kivanc - Pigs are vital to global agriculture, and infectious diseases cause significant economic losses. Leukocytes provide a critical window into the genetic regulation of pig immune traits. However, understanding of these mechanisms within specific immune cell types remains insufficient. Here, we integrate 11 immune traits and systematically map the regulatory landscapes of expression quantitative trait loci (eQTLs), splicing QTLs (sQTLs), and alternative polyadenylation QTLs (apaQTLs) in porcine peripheral blood mononuclear cells (PBMCs) and neutrophils to uncover cell type-specific patterns. These molecular QTLs (molQTLs) exhibit strong cell-type specificity and preferentially regulate genes involved in cross-cell communication that are linked to core immunity, thereby shaping immune phenotypes through intercellular networks. Furthermore, we identify 588 molQTLs that colocalize with genome-wide association study signals for phagocytic capacity. Among these, 60.3% of apaQTLs independently modulate immune traits, including the variant rs330263631. Experiments confirm that rs330263631 modulates mRNA stability and expression levels of the TXNDC15 by dynamically selecting polyadenylation sites and altering the length of the 3' untranslated region. This work systematically delineates the PBMC- and neutrophil-specific genetic architecture underlying immune regulation in pigs and provides a molecular foundation for deciphering the genetic mechanisms of porcine immune traits. - Source: PubMed
Publication date: 2026/02/11
Yang JinyanChen SiqianTang YongjieWang XiniWang LuluLiu HuataoMa FupingZhao QingyaoXing KaiYu YingWang Chuduan - To determine whether TXNDC15 variation causes Meckel-Gruber syndrome (MKS), we assessed the pathogenicity of the frameshift variant c.560delA. A CRISPR-Cas9 generated mouse model carrying the equivalent Txndc15 c.512delA mutation was analyzed at embryonic day 15.5. Homozygous Txndc15 embryos displayed the complete MKS phenotype-fetal lethality, exencephaly, omphalocele, post-axial polydactyly, and polycystic kidneys-together with markedly reduced TXNDC15 protein in brain, liver, and kidney. These findings confirm TXNDC15 as a bona fide MKS disease gene. - Source: PubMed
Liu YangWang HuiChen LiyuanWu XiaoxiaXu ZhiyongHuang QingfaZhang HuCao XiushuLiang XinyuanZhong XingjianLuo Caiqun - Although genome-wide association studies (GWAS) have identified numerous common genetic risk variants for Parkinson's disease (PD), the underlying biological mechanisms remain largely unresolved. - Source: PubMed
Publication date: 2026/01/08
Lim Amanda Wei-YinFoo Jia-NeeChew Elaine Guo-YanLim Shen-YangTan Ai HueyHwang Liang-DarMacGregor StuartRentería Miguel EOng Jue-Sheng - Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration, joint inflammation, and bone hyperplasia. Clonal hematopoiesis of indeterminate potential (CHIP) refers to the presence of cancer-related variants in blood cells of individuals without malignancies. However, it is unclear whether the proinflammatory state induced by CHIP affects the onset of OA. Thus, we investigated CHIP as a risk factor for OA. Here, we analyzed whole-exome sequence (WES) data from 45,380 UK Biobank participants without OA at baseline to identify CHIP. Multivariate Cox regression models were used to evaluate the association between CHIP and incident OA as well as different sites of OA onset. Additionally, enrichment and mediation analyses were conducted on 1463 unique protein datasets to identify protein markers and biological pathways related to both CHIP and OA. We found that the incidence of OA was higher in individuals with CHIP than in those without CHIP. Importantly, individuals with CHIP and VAF > 10% had an increased risk of OA (hazard ratio [HR], 1.46; 95% CI, 1.28-1.68; P < 0.001). The results of classification of OA sites showed that polyarticular OA and hip OA were most significantly associated with CHIP. In addition, analysis of OA and CHIP-related expression proteins and pathways revealed that both were mainly involved in extracellular matrix organization, inflammation, and metabolic pathways. Moreover, the proteomic analysis results suggested that CHIP may influence the occurrence of OA by affecting seven proteins: CD5, CD79B, CEACAM1, FOLR2, LILRA5, SIRPB1, and TXNDC15. CHIP is significantly associated with the risk of incident OA and may exacerbate the progression of OA through inflammatory and immune response mechanisms. This research provides new insights into the pathogenesis of OA, offering a theoretical basis for the early prevention of OA, although a causal relationship remains to be investigated. - Source: PubMed
Publication date: 2025/08/19
Li PingKang ZijianMa RuiqiZhu ChenZhu YingTang IrisZhang JianzhengLi KaiTong Qiang