Ask about this productRelated genes to: SLC25A46 antibody
- Gene:
- SLC25A46 NIH gene
- Name:
- solute carrier family 25 member 46
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 5q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-09-21
- Date modifiied:
- 2019-04-23
Related products to: SLC25A46 antibody
Related articles to: SLC25A46 antibody
- : Allergic rhinitis is common and clinically heterogeneous, but the genes whose genetically regulated immune-state expression influences susceptibility remain incompletely resolved. : We integrated dynamic CD4+ T cell eQTL data (46 activation-state profiles) with allergic rhinitis GWAS summary statistics, applying transcriptome-wide Mendelian randomization (MR), colocalization, SMR/HEIDI, metabolite screening, paired single-cell RNA-seq and TCR analysis, and computational follow-up. Colocalization support was prespecified as conditional ratio PP.H4/(PP.H3 + PP.H4) > 0.7; HEIDI at > 0.05. : After MHC-region exclusion, 50,654 gene-profile pairs were tested and 129 MR-significant genes were identified. Colocalization supported 418 pairs (111 genes); 70 genes passed both SMR and HEIDI; and cross-database comparison yielded a nine-gene overlap set. In GSE200107, baseline good-versus-poor responder differences were larger than treatment-induced transcriptional change; patient-level reanalysis found no pair surviving multiple-testing correction ( = 4 vs. 3); these findings are hypothesis-generating. Paired TCR analysis suggested greater clonotype renewal in good responders (descriptive). Structure-guided screening prioritized unvalidated binder candidates for SLC25A46 and TLR1 (TLR1 TIR docking -5.86 kcal/mol; MD RMSD 0.20 nm). : An exploratory metabolite screen yielded nominally significant indirect-effect signals, but the candidate metabolite did not colocalize with the disease locus. This framework prioritizes candidate therapeutic targets for allergic rhinitis. - Source: PubMed
Publication date: 2026/09/15
Gu WeiLi JingleiLiu ChuanChen ChuanWang Jian - BackgroundThe gene encodes a mitochondrial carrier protein previously implicated in neuropathy and optic atrophy. Biallelic variants in have been described in patients with Parkinson's disease (PD) with optic atrophy, but the evidence supporting a role in PD remains limited.ObjectiveTo assess whether variants contribute to PD, REM sleep behavior disorder (RBD), or dementia with Lewy bodies (DLB).MethodsWe examined common variants using four representative PD genome-wide association studies (GWAS) and an RBD GWAS and applied summary-data-based Mendelian randomization (SMR) to evaluate whether genetically regulated expression of shows a causal association with the risk of PD or RBD. Rare variant analyses were conducted in four cohorts of European descent: Accelerating Medicines Partnership: Parkinson's Disease (AMP-PD) PD (3,051 PD, 3,667 controls), UK Biobank (3,267 PD, 14,939 proxy, 54,800 controls), RBD (1,376 RBD, 2,580 controls), and AMP-PD DLB (2,605 DLB, 1,894 controls). Optimal sequence kernel association test (SKAT-O) and meta-analysis were used to assess rare variants.ResultsNo associations were observed between variants and PD, RBD, or DLB. SMR analyses revealed no evidence supporting a causal relationship between expression and PD or RBD risk. Rare variant burden analyses did not identify significant associations after multiple-testing correction across cohorts or meta-analyses.Conclusion variants showed no evidence of association, suggesting the gene does not play a major role in PD, RBD, or DLB risk. - Source: PubMed
Publication date: 2026/08/06
Yu HanParlar Sitki CemSenkevich KonstantinSomerville Emma NZhang ZhaoLiu LangTeferra MeronAhmad JamilAsayesh FarnazRouleau Guy AGan-Or Ziv - Primary mitochondrial diseases (PMD) have limited disease-modifying therapies, currently applicable to only 3 of over 400 discrete gene disorders. Cycloheximide (CHX) is a global cytosolic translation inhibitor we previously reported to rescue PMD preclinical models, although its toxicity precluded clinical development. To identify specific mediators underlying CHX treatment benefit in PMD, SOMAscan-based proteomics was performed in complex I deficient and genetic disease fibroblast cell line models grown in galactose. Thrombopoietin (THPO) and insulin-like growth factor binding protein 5 (IGFBP5) were the only two differentially regulated proteins, together with ERK/MAPK pathway dysregulation, identified upon CHX treatment in PMD versus healthy control cells. THPO inhibition by siRNA or pharmacologic approaches rescued stress-induced viability loss in patient fibroblasts having diverse PMD gene etiologies, and significantly improved mitochondrial stress, linear growth, and neuromuscular function in a classical model. IGFBP5 overexpression by lentiviral or mRNA approaches rescued cell viability across distinct PMD gene etiologies, as did IGF1 pharmacologic inhibition across both PMD mutant and models. MAPK pharmacologic inhibition rescued multiple distinct complex I disease cells' survival, as well as mitochondrial stress in . Combination therapies targeting multiple of these glucose signaling pathway proteins, together with glucose and N-acetylcysteine, yielded superior therapeutic benefit in complex I disease cell and models. Additionally, single or combined pharmacologic inhibition of THPO or IGF1 significantly enhanced primary and metastatic osteosarcoma cell death. Collectively, targeted small molecule and genetic modulation of THPO, IGF1, or MAPK recapitulated the significant therapeutic benefit of CHX in PMD, while avoiding global translation inhibition. These novel PMD therapies likely confer benefit by attenuating MAPK-driven autophagy and potentially promoting noncanonical glucose uptake, improving cellular energy balance. Overall, these glucose signaling cellular pathway targets hold broad therapeutic promise for PMD patients, warranting further clinical research development. - Source: PubMed
Publication date: 2026/07/24
Keith KelseyPeng MinRemes CristinaMiranda VictoriaWachowski NicholasKose MelisDharaskar ShrikantHaroon SuraiyaVelasco Agustin BSivaramakrishnan PriyaIadarola DonnaDugar SundeepFalk Marni J - SLC25A46 is a mitochondrial intermembrane bridging protein reported to play a crucial role in mitochondrial network maintenance, yet its functional roles in human cancer metabolic rewiring and disease progression remain unexplored, including ovarian cancer (OC). Here, we revealed that SLC25A46 is markedly upregulated in OC and associated with poor patient outcomes. Functionally, SLC25A46 promoted OC growth by facilitating cell proliferation and ferroptosis evasion. Mechanistically, SLC25A46 promotes cell proliferation and ferroptosis evasion of OC cells by activating fatty acid oxidation-mediated ATP and NADPH production via protecting carnitine-acylcarnitine translocase (CACT) from MARCHF5-mediated ubiquitin-degradation. Notably, knockdown of SLC25A46 significantly increased the sensitivity of OC cells to ferroptosis and enhanced their cytotoxic response to carboplatin. Additionally, we found that PBX1 directly binds and transactivates the SLC25A46 promoter. Overall, our results highlight the critical role of SLC25A46/MARCHF5/CACT axis in facilitating cell proliferation and ferroptosis evasion in OC cells via activating fatty acid oxidation-mediated ATP and NADPH production. These findings suggest that targeting SLC25A46 represents a rational strategy to improve treatment outcomes in OC patients. - Source: PubMed
Publication date: 2026/07/20
Gao YungeHao JiataoZhang XiaohongLong MeitingFeng YujingLiu XiaoyueLi XuejianLiu ShujuanGuo XinLv Xiaohui - Aging is the strongest risk factor for Alzheimer's disease (AD); however, some individuals age without major cognitive decline, suggesting that resilience and vulnerability may be associated with distinct molecular trajectories. To investigate these trajectories, we performed an integrated transcriptomic analysis of human dermal fibroblasts (GSE113957) and multi-region brain profiles (GSE48350), extending previous dataset-specific studies that focused primarily on age prediction, regional variation, or synaptic/immune signatures. Healthy aging and AD were compared within a novel antagonistic pleiotropy (AP) framework. This approach prioritized genes and candidate transcriptional regulators with opposing age and disease-associated expression patterns. Across tissues, healthy aging was associated with relative preservation of metabolic, mitochondrial, and lipid-homeostatic programs, whereas AD was associated with suppression of these programs alongside greater inflammatory and immune pathway activity. AP-Vulnerability genes (Age↓/AD↑), including TAC1, FREM3, and SLC25A46, declined with age but were induced in AD. Conversely, AP-Resilience genes (Age↑/AD↓), including PTH2, PPDPF, and NEFH, increased during healthy aging but were reduced in AD. Pathway analyses suggested an association between metabolic programs and resilience, and between immune activation and vulnerability. Transcription-factor inference prioritized PPARG, NFE2L2, and TEAD4 as candidate resilience-associated regulators, showing directionally opposite patterns relative to immune- and developmental-related regulators in AD. - Source: PubMed
Publication date: 2026/06/08
Salihoglu RanaCan ŞehnazDandekar ThomasBencurova Elena