Ask about this productRelated genes to: MTHFD1L antibody
- Gene:
- MTHFD1L NIH gene
- Name:
- methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like
- Previous symbol:
- FTHFSDC1
- Synonyms:
- DKFZP586G1517, FLJ21145
- Chromosome:
- 6q25.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-27
- Date modifiied:
- 2017-06-13
Related products to: MTHFD1L antibody
Related articles to: MTHFD1L antibody
- Hepatocellular carcinoma (HCC) originates from damaged hepatocytes in chronic liver injury. Though HCC development requires oncoproteins-mediated p53 inhibition, both genetic deletion and continous activation of p53 specifically in mouse hepatocytes are shown to promote liver tumorigenesis, suggesting that chronic liver injury firstly activates p53, and p53 activity needs to be dynamically regulated for preventing hepatocarcinogenesis. Yet, it remains unaddressed how liver injury stresses trigger signaling pathways to rapidly activate p53 prior to its inactivation in a physiological setting. Two pathways, ribosomal proteins (RPs)-MDM2 and 14-3-3-MDMX, are shown to activate p53 upon stresses, and mutations of MDM2 or MDMX that may disrupt these pathways have been found in human cancers including HCC. Using our unique double knock-in (DKI) mice that contain wild-type p53 while harbor defects in these two pathways, we unveiled that basal level of p53 in DKI mice is sufficient for maintaining liver function, however, carcinogen- or unhealthy diet-induced HCC initiation is accelerated in DKI mice. The two p53-pathways are also activated in human cirrhotic livers. We futher identified a one-carbon metabolism (1CM) enzyme methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L) as the p53-suppressed player in HCC initiation. We found that MTHFD1L is upregulated in human early HCC and correlated with p53 status, and promotes mouse HCC initiation by enhancing autonomous growth and immune evasion of HCC initiating cells (HCICs). With Nanopore RNA-m A-sequencing, we unveiled that MTHFD1L fulfills these bi-functions by fueling methionine cycle that produces methyl groups to maintain the mRNA m A of Snail (an HCC early tumorigenesis driver) and B2m (a light chain of MHC-I required for antigen presentation to CD8+ T) in HCICs. Our findings demonstrate that the two stress-triggered p53-pathways are crucial for preventing liver early tumorigenesis by reversing MTHFD1L upregulation-associated 1CM reprogramming and subsequent Snail and B2m mRNA-m A-mediated cell autonomous growth and immune evasion. - Source: PubMed
Publication date: 2026/04/30
Lu HuaZhang Yi-WeiPeng GangLiao WenjuanJung Ji HoonLi CaiyueLiu YunlongGao HongZha YitianPham NathanMeaderis StephenEslter EvanZhang YanpingDhar DebanjanZeng Shelya - Chronic fatigue is a debilitating symptom linked to mitochondrial dysfunction which lacks comprehensive genetic insights. This study aims to investigate mitochondrial-related genes associated with chronic fatigue and explores therapeutic targets. We conducted summary-data-based Mendelian randomization (SMR) and Bayesian colocalization analyses using blood eQTL data (n = 31,684) and fatigue GWAS data (n = 449,019). Mitochondrial-related genes were sourced from MitoCarta3.0. Two-sample Mendelian randomization (TSMR) analysis and gene expression detection in rat models of fatigue were employed to enhance the robustness of our findings. Drug-gene interactions were screened via Drug SIGnatures (DSigDB) database and DrugBank database, followed by molecular docking and phenome-wide association study (PheWAS) for safety and pleiotropic effects evaluation. SMR identified nine mitochondrial-related genes, with AKAP10 (OR = 1.012) and MTHFD1L (OR = 1.027) showing robust colocalization and causal links to chronic fatigue. TSMR analysis also indicated significant causal relationships of AKAP10 (OR = 1.017, 95% CI = 1.011-1.023, p = 8.15e-08) and MTHFD1L (OR = 1.046, 95% CI = 1.002-1.091, p = 0.041) with chronic fatigue. Consistently, in fatigue model rats, the expression levels of Akap10 and Mthfd1l were significantly upregulated in both hippocampal and quadriceps tissues (p = 0.021, p = 0.003, p = 0.027, p = 0.001, respectively). Molecular docking revealed strong binding affinities (below -7.0 kcal/mol) between AKAP10, MTHFD1L and repurposed drugs (e.g., irinotecan, digoxin). PheWAS indicated that both AKAP10 and MTHFD1L exhibit no significant associations with other traits at the gene level. Mitochondria-related genes AKAP10 and MTHFD1L are promising targets for the treatment of chronic fatigue. Structural modification of existing drugs targeting these genes may lead to novel therapeutic approaches, which warrants further molecular and pharmacological validation to confirm their potential application in fatigue treatment. - Source: PubMed
Publication date: 2026/04/29
Zhang ZehanXiao ZhuoyangMei HetingQi JunGao YunanZhang YifeiLi Feng - Major depressive disorder (MDD) is a prevalent psychiatric disorder, and its pathophysiology is related to immune dysregulation. The use of genetic evidence to identify molecular targets of specific immune cell types will provide new directions for the development of precision immunotherapy. We integrated single-cell cis-eQTL data for 14 immune cell subtypes from the OneK1K cohort with MDD GWAS summary statistics. We assessed the causal effect of genetically predicted immune cell-specific gene expression on depression using single-cell transcriptome-wide Mendelian randomization (scTWMR), followed by Bayesian colocalization. Functional analyses included enrichment, protein-protein interaction, phenome-wide association, and druggability assessment. We identified six significant gene-cell associations across CD4 T cells, immature B cells, and plasma cells. Three genes showed strong colocalization evidence (PPH > 80%): PTCH1 (CD4 NC, OR = 1.17, P-FDR = 3.78 × 10), MTHFD1L (plasma cells, OR = 1.11, P-FDR = 5.20 × 10), and RP11-293M10.2 (CD4 NC, OR = 0.91, P-FDR = 7.96 × 10). Enrichment implicated Hedgehog signaling and folate metabolism. Drug repurposing highlighted metabolites targeting MTHFD1L and approved drugs targeting PTCH1 warranting further investigation. This study provides evidence for a genetically predicted causal relationship between immune cell-specific gene expression and MDD, which not only constructs a screening framework for candidate gene drug targets but also validates and finds potential drug targets. - Source: PubMed
Mo XinSun DongrenLi FangfangWang DanqiLiao Yiwei - Bladder cancer is one of the most common malignancies of the urinary tract. Among its subtypes, muscle invasive bladder cancer (MIBC) is particularly aggressive and often associated with poor prognosis. The efficacy of platinum-based neoadjuvant chemotherapy and radical cystectomy remains unsatisfactory. In recent years, immune checkpoint inhibitors have shown promising therapeutic potential in MIBC. However, reliable biomarkers for predicting treatment response are still lacking. Moreover, traditional clinical parameters, such as TNM staging, often fail to accurately assess patient outcomes. Therefore, identifying novel biomarkers is crucial for improving prognosis and optimizing treatment strategies in MIBC. - Source: PubMed
Publication date: 2026/04/14
Peng SiqiaoLiu YuHuang PeishengLiu QinweiZhang LeHsu Cheng-YaZeng YanruLu JianmingZhao HaiboCai Chao - Advanced renal failure remains a major global health burden. Mitochondrial dysfunction is frequently observed during progressive kidney injury and chronic allograft dysfunction (CAD), but observational data cannot distinguish causal involvement from secondary consequences. We applied a multi-omic genetic prioritization framework to evaluate whether inherited variation affecting mitochondrial gene regulation is associated with a proxy phenotype for advanced renal failure and fibrotic allograft remodeling. - Source: PubMed
Publication date: 2026/03/27
Shen QinghuanDing RunminWen ZhiyuFeng DengyuanZhang JianjianLiu JiawenHan QianguangSun LiChen HaoFei ShuangXu ZhenHao RuijinlinTan Ruoyun