ACSL6
- Known as:
- ACSL6
- Catalog number:
- 001049A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACSL6
Related genes to: ACSL6
- Gene:
- ACSL6 NIH gene
- Name:
- acyl-CoA synthetase long chain family member 6
- Previous symbol:
- FACL6
- Synonyms:
- KIAA0837, ACS2, LACS5, LACS2
- Chromosome:
- 5q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-09-14
- Date modifiied:
- 2017-06-13
Related products to: ACSL6
Related articles to: ACSL6
- Genome-wide association studies (GWASs) have identified numerous loci associated with Alzheimer's disease (AD), yet the effector genes and regulatory mechanisms underlying many of these associations remain unresolved. This challenge is particularly pronounced for non-coding variants, whose regulatory effects may extend over long genomic distances and cannot be reliably inferred from the nearest gene alone. Here, we developed an integrative computational framework that incorporates three-dimensional chromatin interactions, expression quantitative trait loci (eQTL), and sequence-level regulatory annotations to identify candidate effector genes at AD-associated loci. AD-associated lead single-nucleotide polymorphisms (SNPs) and variants in strong linkage disequilibrium were mapped to enhancer elements and promoter-interacting regions using publicly available Hi-C and promoter capture Hi-C data from the hippocampus and cerebral cortex. Hi-C-derived enhancer-promoter relationships were inferred using PSYCHIC, whereas significant promoter-centered interactions from promoter capture Hi-C were used to connect variant-containing regions with candidate effector genes. The resulting SNP-gene relationships were further evaluated using brain-relevant eQTL evidence and predicted allele-dependent alterations in transcription factor binding motifs. This integrative analysis identified 608 unique candidate regulatory target genes supported by spatial chromatin contacts and complementary regulatory evidence, including genes not necessarily assigned by conventional nearest-gene annotation. Functional enrichment analysis indicated that the prioritized genes were involved in biological processes relevant to AD pathophysiology. Detailed analyses of three representative SNP-gene pairs, rs2373115-, rs6656401-, and rs3776011-, further illustrated how chromatin interaction, expression-associated, and sequence-level evidence can be combined to formulate locus-specific regulatory hypotheses. These findings represent computationally inferred and associative regulatory relationships rather than experimentally validated causal effects. They provide a structured framework for refining post-GWAS interpretation of non-coding AD risk loci and prioritizing candidate targets for further experimental validation. - Source: PubMed
Publication date: 2026/09/20
Li HaitaoWang ZhenLiu XinSun Xiao - Hyperuricemia (HUA) and gout in goslings are increasingly recognized in intensive production systems, yet liver involvement in HUA remains poorly understood. This study examines how a high-protein diet influences gosling HUA through liver transcriptional and metabolic alterations. In Exp. Ⅰ, a total of 80 one-d-old male goslings (93.13 ± 0.96 g) were randomly assigned to four dietary treatments containing 18% (control group), 21% (P21 group), 24% (P24 group), and 27% (P27 group) crude protein (CP), with four replicates of five birds per treatment, for an 18-d experimental period to establish a HUA model. Goslings fed the 24% CP diet exhibited joint swelling, sparse plumage, and white feces, accompanied by reduced average daily gain (ADG; = 0.011) and average daily feed intake (ADFI; < 0.001). Serum uric acid ( = 0.005), xanthine oxidase (XOD; = 0.009), xanthine dehydrogenase (XDH; = 0.018), aspartate aminotransferase (AST; < 0.001), urea ( < 0.001), interleukin-1β (IL-1β; = 0.010), and tumor necrosis factor-α (TNF-α; < 0.001) levels were significantly elevated in the P24 group, consistent with HUA-associated metabolic and inflammatory alterations. In Exp. Ⅱ, a total of 40 one-d-old goslings (93.88 + 0.92 g) were randomly assigned to two groups ( = 20 per group) and fed an 18% CP basal diet (CON group) or a 24% CP diet (HUA group) for 18 d. The HUA group showed increased liver index ( = 0.001), hydropic and partial lipid degeneration, hepatocyte swelling, and marked mitochondrial swelling observed by transmission electron microscopy (TEM). Integrated transcriptomics and metabolomics of the liver revealed that decreased levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 8(S)-hydroxyeicosatetraenoic acid [8(S)-HETE] were associated with suppression of the peroxisome proliferator-activated receptor α/γ (PPARα/γ) signaling pathway. Meanwhile, the upregulation of and was linked to a 2.61-fold increase in adenosine monophosphate (AMP) accumulation. Elevated and expression enhanced AMP-to-inosine conversion (1.69-fold), and coordinated up-regulation of , , and further accelerated UA formation in purine metabolism, collectively contributing to HUA and associated inflammatory responses. Although graded increases in dietary CP induced proportional shifts in digestible amino acid concentrations, these results reveal a strong correlation between high-protein diets and HUA, as well as subsequent liver and renal injuries in goslings. - Source: PubMed
Publication date: 2026/08/04
Li XifengXie YufeiZhang MengyaoZou TaoZhong ChonghuaRajput Zahid IqbalBi ShichengCao Liting - ETV6-rearranged acute lymphoblastic leukemia (ALL) is associated with poor prognosis in adults. Previously, a super-enhancer (SE) located within the ETV6 intragenic region (ETV6-SE) was identified in a rare fusion gene, ETV6::ACSL6, but further work is needed to determine whether ETV6-SE is broadly present in ALL and how ETV6 rearrangements impact the SE function. Here, we demonstrated that ETV6 functions as a regulatory element via ETV6-SE in ALL, with CDKN1B as a key target. CRISPR interference and knockout experiments revealed the core enhancer region within ETV6-SE responsible for CDKN1B regulation. ETV6 rearrangements disrupted ETV6-SE and impaired long-range chromatin interaction with the CDKN1B locus, leading to its downregulation that in turn activated the NF-κB pathway and increased expression of anti-apoptotic proteins BCL-2/BCL-XL. In patient-derived xenograft (PDX) models, pharmacological inhibition of BCL-2/BCL-XL using venetoclax or navitoclax showed additive effects when combined with dexamethasone. Collectively, these findings establish the ETV6-SE-CDKN1B regulatory axis as a mechanism contributing to treatment resistance in ETV6-rearranged ALL. - Source: PubMed
Publication date: 2026/07/29
Xu WenqianMa XiaofangSun XueSong GaoxianZhu ShuhanTian JieShi RuiruiGuo Linlang - Polygenic scores (PGSs) stratify disease risk but often fail to capture individual variation. "Misaligned" individuals, whose observed phenotypes deviate from their genetically expected values based on PGS, provide a powerful model for identifying factors beyond common-variant effects, including additional genetic factors. Here, we apply misalignment classification and enrichment testing frameworks to seven continuous traits and three diseases, assessing whether misaligned individuals in the UK Biobank are enriched for rare (minor-allele frequency [MAF] <0.1%) damaging genetic variation. We identified significant enrichment of predicted loss-of-function (pLoF) variants in COPB2 and GORAB among individuals with lower-than-expected bone mineral density. Regarding stature, shorter-than-expected individuals were enriched for pLoF variants in ACAN and IGF1, while taller-than-expected individuals showed enrichment for damaging missense variants in FBN1. Transitioning from validation to discovery, we performed an exome-wide scan for genes associated with misalignment and identified 74 significant genes, including KANK1, a gene which may have a protective role against primary ovarian insufficiency, and ACSL6, a lipid metabolism gene where damaging missense variation was associated with lower-than-expected BMI. For diseases, results supported a liability threshold model involving counteracting common and rare variant effects. Diagnosed type 2 diabetes mellitus patients with rare pathogenic variants in HNF1A and HNF4A possessed significantly lower polygenic risk than those without. Conversely, coronary artery disease controls harboring protective ANGPTL3 variants had nominally higher polygenic risk. This study highlights the power of misalignment-based analyses in complex continuous phenotypes and disease with the potential to validate known genetic contributors to traits and identify previously unassociated genes. - Source: PubMed
Publication date: 2026/06/22
Baya Nikolas ALassen Frederik HHill BarneyVenkatesh Samvida SCurrant HannahLindgren Cecilia MPalmer Duncan S - Acyl-CoA synthetase long-chain family member 6 (ACSL6) is a member of the long-chain acyl-CoA synthetase (ACSLs) family that is particularly expressed in nervous system. It mainly catalyzes the activation reaction of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA), providing substrates for the synthesis and remodeling of neuronal membrane lipids. Recent studies have shown that ACSL6 plays a decisive role in DHA enrichment, synaptic plasticity and antioxidant defense in the brain. Its dysfunction can lead to changes in membrane lipid composition, weakened synaptic signals and excessive activation of neuroinflammation, thereby causing neurological deficits like cognitive and motor disorders. This review comprehensively summarizes the molecular structure characteristics and catalytic mechanism of ACSL6, and analyzes the roles of its different domains in substrate recognition and reaction regulation. ACSL6 participates in lipid metabolism by converting DHA into DHA-CoA, forming a local DHA metabolic pathway and providing continuous energy supply for the structural stability and signal transmission of nerve membranes. The localization characteristics of ACSL6 enable the spatial directional distribution of DHA in the synaptic membrane and endoplasmic reticulum regions, which is a key link in maintaining brain lipid homeostasis. In addition, ACSL6 is involved in the defense mechanisms of the nervous system by regulating oxidative stress responses, ferroptosis and inflammatory pathways. Its dysregulation has been confirmed to be associated with various neurodegenerative diseases. A thorough clarification of the molecular mechanism of ACSL6 may provide a new theoretical basis and highlight potential avenues for future therapeutic exploration regarding the imbalance of lipid homeostasis in neurons and related diseases. - Source: PubMed
Publication date: 2026/05/30
Zhang ShaoyangMeng FangyuYuan YuhangXiong HongyuMu FaqinLi XiangWu LingqiaoYang XiaopengLi XingyuMu YizheChen CeshiWu HuixinZhang Yuan