Ask about this productRelated genes to: TMEM141 Blocking Peptide
- Gene:
- TMEM141 NIH gene
- Name:
- transmembrane protein 141
- Previous symbol:
- -
- Synonyms:
- MGC14141
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2006-03-21
- Date modifiied:
- 2015-08-26
Related products to: TMEM141 Blocking Peptide
Related articles to: TMEM141 Blocking Peptide
- Metabolic dysfunction-associated steatoic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), have become a global epidemic due to obesity and genetic susceptibility. Here, we report transmembrane protein 141 (TMEM141), a protein with a largely unknown function, as a key regulator of MASH and MASH-associated fibrosis. Hepatic TMEM141 is reduced in MASLD/MASH patients and mouse models of MASLD/MASH due to increased microRNA-149. Unexpectedly, genetic inactivation of hepatocyte TMEM141 protects against MASLD/MASH induced by a high fat/cholesterol/fructose (HFCF) diet, whereas hepatic overexpression of human TMEM141 exacerbates MASLD/MASH. We further show that TMEM141 localizes within mitochondria and interacts with mitochondrial complex I to regulate ROS production. Inactivation of TMEM141 reduces ROS production, induces hepatocyte nuclear factor 4α (HNF4α), and fails to protect against HFCF diet-induced MASH or fibrosis in the absence of hepatocyte HNF4α. Finally, pharmacological inhibition of hepatic TMEM141 by N-acetylgalactosamine (GalNAc)-siTmem141 significantly promotes the reversal of HFCF diet-induced MASH and fibrosis. These findings underscore a critical role of TMEM141 in MASH development and suggest that targeting hepatic TMEM141 may represent a promising strategy for treating MASH and MASH-associated fibrosis. - Source: PubMed
Publication date: 2026/07/13
Wang JiayouChen Chwen-LihGopoju RajaHu ShuweiWang YangWang HuiBatayneh ZaidPan XiaoliChen Yeong-RennMellott JeffreyKang PatrickGunawardana LakshithaYin LiyaZhang Yanqiao - How mitochondrial respiration is tightly regulated by energy demand remains incompletely defined. When mammalian cells switch from glucose to galactose as a carbon source, we observed the enhanced assembly of respiratory chain complexes accompanied by a marked reduction in TMEM141, a mitochondrial inner membrane protein. Loss of TMEM141 increased mitochondrial respiration and promoted complex I assembly, whereas galactose-induced complex I assembly was markedly blunted in TMEM141-deficient cells. TMEM141 interacts with the complex I assembly factor TIMMDC1, limiting its association with complex I subunits. TMEM141 is degraded by the mitochondrial proteases AFG3L2 and YME1L1, and galactose treatment strengthens their interactions. TMEM141 deficiency increases oxidative damage and mtDNA release, leading to activation of the cGAS-STING pathway. In Drosophila, dTMEM141 localizes to mitochondria, modulates mitochondrial activity, and is required for glial cell integrity in the eye. Together, our findings reveal TMEM141 as a negative regulator of complex I assembly that adapts to oxidative phosphorylation (OXPHOS) demands. - Source: PubMed
Publication date: 2026/06/26
Li ZhirongChen NuoZhou CaixiaXu LingnaWang XiyuanXu HongShang WeinaLiu Jun-PingWang LiquanTong Chao - Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141 mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID. - Source: PubMed
Publication date: 2023/10/14
Sun LiweiYang XuetingKhan AmjadYu XueZhang HanHan ShiruiHabulieti XiaerbatiSun YangWang RongrongZhang Xue - The Dongxiang Blue-shelled chicken is one of the most valuable Chinese indigenous poultry breeds. However, compared to the Italian native White Leghorn, although this Chinese breed possesses numerous favorable characteristics, it also exhibits lower growth performance and fertility. Here, we utilized genotyping sequencing data obtained via genome reduction on a sequencing platform to detect 100,114 single nucleotide polymorphisms and perform further biological analysis and functional annotation. We employed cross-population extended haplotype homozygosity, eigenvector decomposition combined with genome-wide association studies (EigenGWAS), and efficient mixed-model association expedited methods to detect areas of the genome that are potential selected regions (PSR) in both chicken breeds, and performed gene ontology (GO) enrichment and quantitative trait loci (QTL) analyses annotating using the Kyoto Encyclopedia of Genes and Genomes. The results of this study revealed a total of 2424 outlier loci (-value <0.01), of which 2144 occur in the White Leghorn breed and 280 occur in the Dongxiang Blue-shelled chicken. These correspond to 327 and 94 PSRs containing 297 and 54 genes, respectively. The most significantly selected genes in Blue-shelled chicken are and , while the gene, related to eggshell color, was identified via EigenGWAS. We show that the White Leghorn genes , , , , , , , and are involved in immunity, reproduction, and growth, and thus might represent footprints of the selection process. In contrast, we identified six significantly enriched pathways in the Dongxiang Blue-shelled chicken that are related to amino acid and lipid metabolism as well as signal transduction. Our results also reveal the presence of a GO term associated with cell metabolism that occurs mainly in the White Leghorn breed, while the most significant QTL regions mapped to the Chicken QTL Database (GG_4.0) for the Dongxiang Blue-shelled breed are predominantly related to lesions, bone mineral content, and other related traits compared to tibia length and body weight (, at 14, 28, 42, and 70 d) in the White Leghorn. The results of this study highlight differences in growth, immunity, and egg quality traits between the two breeds, and provide a foundation for the exploration of their genetic mechanisms. - Source: PubMed
Publication date: 2018/02/02
Zhao Qing-BoLiao Rong-RongSun HaoZhang ZheWang Qi-ShanYang Chang-SuoZhang Xiang-ZhePan Yu-Chun - We have used unique population-based data resources to identify 22 high-risk extended pedigrees that show clustering of suicide over twice that expected from demographically adjusted incidence rates. In this initial study of genetic risk factors, we focused on two high-risk pedigrees. In the first of these (pedigree 12), 10/19 (53%) of the related suicides were female, and the average age at death was 30.95. In the second (pedigree 5), 7/51 (14%) of the suicides were female and the average age at death was 36.90. Six decedents in pedigree 12 and nine in pedigree 5 were genotyped with the Illumina HumanExome BeadChip. Genotypes were analyzed using the Variant Annotation, Analysis, and Search program package that computes likelihoods of risk variants using the functional impact of the DNA variation, aggregative scoring of multiple variants across each gene and pedigree structure. We prioritized variants that were: (1) shared across pedigree members, (2) rare in other Utah suicides not related to these pedigrees, (3) < or = 5% in genotyping data from 398 other Utah population controls and (4) < or = 5% frequency in publicly available sequence data from 1358 controls and/or in dbSNP. Results included several membrane protein genes (ANO5, and TMEM141 for pedigree 12 and FAM38A and HRCT1 for pedigree 5). Other genes with known neuronal involvement and/or previous associations with psychiatric conditions were also identified, including NFKB1, CASP9, PLXNB1 and PDE11A in pedigree 12, and THOC1, and AUTS2 in pedigree 5. Although the study is limited to variants included on the HumanExome BeadChip, these findings warrant further exploration, and demonstrate the utility of this high-risk pedigree resource to identify potential genes or gene pathways for future development of targeted interventions. - Source: PubMed
Publication date: 2013/11/19
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