ANO4
- Known as:
- ANO4
- Catalog number:
- 001670A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ANO4
Related genes to: ANO4
- Gene:
- ANO4 NIH gene
- Name:
- anoctamin 4
- Previous symbol:
- TMEM16D
- Synonyms:
- FLJ34221, FLJ34272, FLJ35277
- Chromosome:
- 12q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-17
- Date modifiied:
- 2016-10-04
Related products to: ANO4
Related articles to: ANO4
- Di-2-ethylhexyl phthalate and its bioactive metabolite mono-2-ethylhexyl phthalate (MEHP) are ubiquitous endocrine-disrupting chemicals implicated in carcinogenesis. However, the molecular mechanisms linking MEHP exposure, host genetic susceptibility, and prostate cancer progression remain incompletely defined. We integrated transcriptomic profiling of MEHP-exposed human prostate epithelial cells with a genetic association study of 630 patients with prostate cancer receiving androgen deprivation therapy. MEHP-responsive genes were identified from public microarray datasets and subjected to pathway enrichment analyses. Germline single-nucleotide polymorphisms (SNPs) in MEHP-regulated genes were evaluated for their association with progression-free survival, overall survival, and cancer-specific survival. The clinical and functional relevance of the key genes was further assessed using large-scale public prostate cancer expression datasets. MEHP exposure induced widespread transcriptional reprogramming, prominently suppressing focal adhesion and cell-matrix interaction pathways. Genetic analyses identified multiple prognostically relevant SNPs within MEHP-responsive genes, with anoctamin 4 () variants showing consistent associations across all clinical endpoints. The minor allele of rs17485225 in was significantly associated with reduced all-cause and prostate cancer-specific mortality. Pooled analyses revealed reduced expression levels in prostate cancer tissues and improved survival in patients with high expression levels. Pathway analyses linked low expression levels with enhanced cell cycle activity and compromised cell adhesion. Our findings suggest that may act as a mediator of MEHP-associated prostate cancer progression and support a gene-environment interaction model in which environmental toxicant exposure and germline variation converge on focal adhesion dysregulation to potentially contribute to aggressive disease. - Source: PubMed
Publication date: 2026/03/07
Chang Chi-FenHuang Shu-PinChen Yei-TsungChen Lih-ChyangHuang Chao-YuanYu Chia-ChengLin Victor CLu Te-LingBao Bo-Ying - Previous studies have illuminated a significant genetic component in motor neuron disease (MND) pathogenesis, with several causative genes identified. However, a substantial proportion of MND cases remain genetically unexplained, particularly regarding the comprehensive contribution of rare, high-impact variants across the exome. - Source: PubMed
Publication date: 2026/01/09
Hu ZhenWan Jing-JinYan Qin-QinFan YuLiu Jun - The accumulation of β-amyloid (Aβ) peptides into insoluble plaques is an early pathological feature of Alzheimer's disease (AD). BACE1 is the sole β-secretase for Aβ generation, making it an attractive therapeutic target for AD therapy. While BACE1 inhibitors have been shown to reduce Aβ levels in people with AD, clinical trials targeting BACE1 have failed due to unwanted synaptic deficits. Understanding the physiological role of BACE1 in individual cell types is essential for developing effective BACE inhibitors for the treatment of AD. Recent single-cell RNA transcriptomic assays revealed that oligodendrocytes are enriched with genes required for generating Aβ. However, the contribution of oligodendrocytes to amyloid plaque burden in AD and the side effects of oligodendrocyte-specific Bace1 deletion remain to be explored. - Source: PubMed
Publication date: 2024/11/16
Ishii AkihiroPathoulas Joseph AMoustafaFathy Omar OmarGe YingyingYao Annie YPantalena TressaSingh NeerajZhou JohnHe WanxiaMurphy PatrickYan RiqiangHu Xiangyou - Anoctamins are a family of Ca-activated proteins that may act as ion channels and/or phospholipid scramblases with limited understanding of function and disease association. Here, we identified five de novo and two inherited missense variants in ANO4 (alias TMEM16D) as a cause of fever-sensitive developmental and epileptic or epileptic encephalopathy (DEE/EE) and generalized epilepsy with febrile seizures plus (GEFS+) or temporal lobe epilepsy. In silico modeling of the ANO4 structure predicted that all identified variants lead to destabilization of the ANO4 structure. Four variants are localized close to the Ca binding sites of ANO4, suggesting impaired protein function. Variant mapping to the protein topology suggests a preliminary genotype-phenotype correlation. Moreover, the observation of a heterozygous ANO4 deletion in a healthy individual suggests a dysfunctional protein as disease mechanism rather than haploinsufficiency. To test this hypothesis, we examined mutant ANO4 functional properties in a heterologous expression system by patch-clamp recordings, immunocytochemistry, and surface expression of annexin A5 as a measure of phosphatidylserine scramblase activity. All ANO4 variants showed severe loss of ion channel function and DEE/EE associated variants presented mild loss of surface expression due to impaired plasma membrane trafficking. Increased levels of Ca-independent annexin A5 at the cell surface suggested an increased apoptosis rate in DEE-mutant expressing cells, but no changes in Ca-dependent scramblase activity were observed. Co-transfection with ANO4 wild-type suggested a dominant-negative effect. In summary, we expand the genetic base for both encephalopathic sporadic and inherited fever-sensitive epilepsies and link germline variants in ANO4 to a hereditary disease. - Source: PubMed
Publication date: 2024/05/13
Yang FangBegemann AnaisReichhart NadineHaeckel AkvileSteindl KatharinaSchellenberger EykSturm Ronja FiniBarth MagalieBassani SissyBoonsawat ParanchaiCourtin ThomasDelobel Bruno Gunning BoudewijnHardies KatiaJennesson MélanieLegoff LouisLinnankivi TarjaProuteau ClémentSmal NoorSpodenkiewicz MartaToelle Sandra PVan Gassen KoenVan Paesschen WimVerbeek NienkeZiegler AlbanZweier MarkusHorn Anselm H CSticht HeinrichLerche HolgerWeckhuysen SarahStrauß OlafRauch Anita - Plasma membrane localized anoctamin 1, 2 and 6 (TMEM16A, B, F) have been examined in great detail with respect to structure and function, but much less is known about the other seven intracellular members of this exciting family of proteins. This is probably due to their limited accessibility in intracellular membranous compartments, such as the endoplasmic reticulum (ER) or endosomes. However, these so-called intracellular anoctamins are also found in the plasma membrane (PM) which adds to the confusion regarding their cellular role. Probably all intracellular anoctamins except of ANO8 operate as intracellular phospholipid (PL) scramblases, allowing for Ca-activated, passive transport of phospholipids like phosphatidylserine between both membrane leaflets. Probably all of them also conduct ions, which is probably part of their physiological function. In this brief overview, we summarize key findings on the biological functions of ANO3, 4, 5, 7, 8, 9 and 10 (TMEM16C, D, E, G, H, J, K) that are gradually coming to light. Compartmentalized regulation of intracellular Ca signals, tethering of the ER to specific PM contact sites, and control of intracellular vesicular trafficking appear to be some of the functions of intracellular anoctamins, while loss of function and abnormal expression are the cause for various diseases. - Source: PubMed
Publication date: 2024/04/17
Kunzelmann KarlOusingsawat JirapornSchreiber Rainer