ATP7B
- Known as:
- ATP7B
- Catalog number:
- NB100-361R
- Product Quantity:
- 0.1 ml
- Category:
- -
- Supplier:
- ACR
- Gene target:
- ATP7B
Related genes to: ATP7B
- Gene:
- ATP7B NIH gene
- Name:
- ATPase copper transporting beta
- Previous symbol:
- WND
- Synonyms:
- -
- Chromosome:
- 13q14.3
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-02-10
Related products to: ATP7B
Related articles to: ATP7B
- Cuproptosis is a recently identified form of regulated cell death driven by the direct binding of Cu⁺ to the lipoyl moiety of mitochondrial tricarboxylic acid (TCA) cycle enzymes, leading to dihydrolipoamide S-acetyltransferase (DLAT) oligomerisation, iron-sulfur cluster (Fe-S) protein depletion, and proteotoxic stress, and is uniquely dependent on mitochondrial respiration. This review critically synthesises current evidence on the role of cuproptosis in type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and obesity. In T2DM, three causally validated pathways of copper transporter dysregulation converge on ferredoxin 1 (FDX1)-dependent DLAT oligomerisation, with substantial FDX1 reduction in diabetic skeletal muscle providing quantitative evidence of cuproptotic commitment; however, β-cell-specific knockout studies remain critically absent. In MASLD, indirect reactive oxygen species (ROS)-mediated insulin resistance is favoured over direct copper-receptor interactions. We propose the metabolic threshold hypothesis, positing that cuproptosis represents failed adaptation to chronic lipid overload, triggered when copper influx exceeds the combined buffering capacity of ATPase copper transporting beta (ATP7B)-mediated efflux, metallothionein sequestration, and glutathione (GSH) chelation. The serum Cu/Zn ratio cannot distinguish cuproptosis from ferroptosis; precise identification requires combined detection of FDX1, DLAT, lipoic acid synthase (LIAS), and lipoyltransferase 1 (LIPT1) with mitochondrial copper content, with immunohistochemistry (IHC) for DLAT oligomerisation as the most clinically accessible surrogate marker. Copper chelators including tetrathiomolybdate and merestinib are primary agents for metabolic tissue preservation, whereas ionophores such as elesclomol are restricted to oncology, with lipid nanoparticle-based delivery platforms essential to overcome the blood-brain barrier challenge, as underscored by the neurological worsening documented in D-penicillamine-treated Wilson disease patients. The interplay between cuproptosis and ferroptosis, sharing GSH depletion but diverging at lipoylated protein aggregation versus glutathione peroxidase 4 (GPX4)-dependent lipid peroxidation, suggests dual-pathway inhibition may be necessary. Future priorities include validation of the metabolic threshold hypothesis, β-cell-specific knockout studies, standardised DLAT oligomerisation diagnostics, tissue-targeted copper modulator delivery, and integration of cuproptosis biomarkers with multi-omics and artificial intelligence for clinically stratified precision medicine. - Source: PubMed
Publication date: 2026/07/28
Chen JingFang ChaoTang ShiguoWang Haoran - Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in impaired biliary copper excretion and progressive copper accumulation in multiple tissues. Ocular manifestations represent some of the most characteristic and clinically valuable features of the disease, contributing to diagnosis, monitoring, and assessment of neurological involvement. This narrative review summarizes current knowledge regarding the pathophysiology, clinical presentation, and imaging characteristics of ocular involvement in WD. Copper deposition within the eye occurs primarily through the aqueous humor, leading to accumulation in the corneal Descemet membrane and lens capsule. Kayser-Fleischer rings remain the most prevalent ocular sign being strongly associated with neurological disease, while sunflower cataracts represent a less common but highly characteristic manifestation. Anterior segment optical coherence tomography and in vivo confocal microscopy have recently improved the detection and monitoring of these lesions. Beyond copper deposition, growing evidence indicates that WD is associated with retinal and optic nerve neurodegeneration. Optical coherence tomography studies consistently demonstrate thinning of the retinal nerve fiber layer, ganglion cell complex, and macular structures, particularly in patients with neurological involvement. Electrophysiological investigations, including visual evoked potentials and electroretinography, reveal delayed neural conduction and retinal dysfunction, supporting the concept of widespread neuro-ophthalmological impairment. Optical coherence tomography angiography further identifies microvascular alterations affecting retinal and peripapillary capillary networks. Importantly, several ocular abnormalities correlate with neurological severity and may serve as non-invasive biomarkers of disease progression. Current treatments, including copper chelators and zinc therapy, can induce regression of Kayser-Fleischer rings and sunflower cataracts. Ocular assessment therefore provides a valuable window into systemic and neurological disease activity, highlighting the importance of multidisciplinary management and the potential role of emerging imaging biomarkers in Wilson disease. - Source: PubMed
Publication date: 2026/07/21
Coviltir ValeriaSabo CristinaNicula Ariadna PatriciaMarinescu Maria Cristina - Hepatic ischemia reperfusion injury is an important pathological factor leading to complications after hepatectomy and transplantation. Although cuproptosis has been reported as a new paradigm of programmed death triggered by copper homeostasis imbalance, its regulatory mechanisms and intervention strategies in liver IRI remain to be fully elucidated. The purpose of this study was to reveal the role of cuproptosis in liver IRI, and to elucidate the molecular mechanism by which adipose-derived stem cell exosomes (ADSC-Exos) exert therapeutic effects by regulating copper metabolism. - Source: PubMed
Publication date: 2026/07/15
Cao LeiLi PujunMa YajunLu XiangyuWang YueWang HongbinZhang JiantaoLiu Tao - Ceruloplasmin (Cp) is a multifunctional multicopper oxidase principally produced in the liver and, to a lesser extent, in the central nervous system. It regulates iron homeostasis and oxidative balance, Cp oxidizes ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), thereby enabling its safe integration into transferrin and averting reactive oxygen species formation. Beyond its ferroxidase activity, Cp also serves as a major copper carrier in plasma and contributes to antioxidant defense mechanisms. Although, the imbalance of ceruloplasmin has been gradually recognized as a key marker in the pathogenesis of neurodegenerative disorders. It is associated with neurofibrillary tangles, amyloid plaques, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. In the past, Cp and neuropathology were first established when a decreased level of serum ceruloplasmin was reported as a diagnostic biomarker of Wilson's disease, a disorder characterized by copper build-up triggered by mutations in the ATP7B gene. Furthermore, some studies suggest the absence of Cp was known in aceruloplasminemia, a different neurodegenerative condition characterized by extensive deposition of iron in the brain and progressive neuronal loss. However, several studies have reported that Cp's function and expression undergo important modifications in Alzheimer's, Parkinson's, Wilson's disease, and other neurological conditions. These alterations in Cp are directly linked to disrupted metal homeostasis, alleviating oxidative stress and neuroinflammation. Thus, besides understanding the structural, metabolic, and biological roles of Cp, this review aims at explaining its possible effects on common neurological disorders. The review also focusses on the therapeutic opportunities targeting Cp-mediated pathways, primarily, focusing on how Cp dysfunction interrelates with copper metabolism, iron dysregulation, and neuroinflammatory signalling, as reported in various clinical and experimental studies. Understanding Cp mechanism may highlight novel strategies for overcoming these neurodegenerative diseases. - Source: PubMed
Publication date: 2026/07/21
Kunwar DeepikaKumar JayantAli Syed AfrozNamdeo Ajay GFlora S J S - Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene, resulting in toxic copper accumulation in the body. Diagnosis is typically based on biochemistries, including low serum ceruloplasmin and elevated 24-h urine copper excretion, with Kayser-Fleischer (KF) rings being a supportive feature. We describe a 7-year-old girl who presented with isolated elevation of serum alanine aminotransferase (ALT), low serum ceruloplasmin, and presence of nonspecific autoantibodies. Liver biopsy revealed elevated hepatic copper content (241 μg/g dry weight), mild macrovesicular steatosis, negative copper staining and no KF rings. Targeted genetic testing identified a single pathogenic ATP7B variant, and whole exome sequencing (WES) later revealed a second variant of uncertain significance (VUS). Repeat liver biopsy showed hepatic copper content of 258 mcg/g, meeting diagnostic criteria. The patient was started on trientine, and ALT normalized within 3 months, with increased urinary copper excretion. This case underscores how WD can mimic autoimmune hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD), and how diagnosis may rely on integrating histologic findings, genetic data, and therapeutic response. - Source: PubMed
Publication date: 2026/04/03
Palan Mihir JSimpson DanaMiranda CherylHakar MelanieLin Henry C