Atp7b mutation. Medical search. Frequent questions

Wilson's disease (WD) is an autosomal-recessive disorder caused by ATP7B gene mutations leading to pathological accumulation of copper in the liver and brain. (nih.gov)
Specifically, Wilson disease is an autosomal recessive disorder resulting from a mutation in the ATP7B gene. (childrenscolorado.org)
Wilson disease (WD) [ 1 ] is a disorder of copper metabolism mediated by autosomal recessive inherited mutations of the ATP7B gene on chromosome 13q. (biomedcentral.com)
Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism. (epilepsia.su)
Wilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the ATP7B gene, which are inherited in an autosomal recessive pattern. (researcher.life)
Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene. (chronicliverdisease.org)
Missense mutations causing the rare autosomal neurodegenerative disease aceruloplasminemia were investigated by testing their ability to prevent ferroportin degradation in rat glioma C6 cells silenced for endogenous ceruloplasmin. (uniroma3.it)

Wilson's disease is caused by a mutation in the Wilson disease protein (ATP7B) gene. (wikipedia.org)
WD is caused by mutations in the gene encoding ATP7B, a protein localized to the trans-Golgi network that primarily facilitates hepatic copper excretion. (ru.nl)
The aim of this study was to investigate the possibility that defects arising from some WD mutations are ameliorated by drug treatment aimed at improvement of protein folding and restoration of protein function. (ru.nl)
With the exception of p.S1363F, all mutations tested (p.G85V, p.R778L, p.H1069Q, p.C1104F, p.V1262F, p.G1343V, and p.S1363F) resulted in reduced ATP7B protein expression, whereas messenger RNA abundance was unaffected. (ru.nl)
Retention of mutant ATP7B in the endoplasmic reticulum, increased protein expression, and normalization of localization after culturing cells at 30 degrees C, and homology modeling suggested that these proteins were misfolded. (ru.nl)
Treatment with pharmacological chaperones 4-phenylbutyrate (4-PBA) and curcumin, a clinically approved compound, partially restored protein expression of most ATP7B mutants. (ru.nl)
CONCLUSION: These findings might enable novel treatment strategies in WD by directly enhancing the protein expression of mutant ATP7B with residual copper export activity. (ru.nl)
The ATP7B gene provides instructions for making a protein called copper-transporting ATPase 2. (medlineplus.gov)
About half the mutations change one of the protein building blocks (amino acids) used to make copper-transporting ATPase 2. (medlineplus.gov)
This type of mutation alters the 3-dimensional structure of the protein or its stability, preventing copper-transporting ATPase 2 from functioning properly. (medlineplus.gov)
The primary reason for the disease is mutation in ATP7B or Wilson disease protein. (openpr.com)
Synonymous mutations do not change the protein sequences. (biomedcentral.com)
The fold recognition server Phyre2 ( http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index ) was used to identify the best structural template and domain of ATP7B protein, and molecular graphics were analyzed by Pymol software. (beingmedicos.com)
ProtParam ( http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index ) and Protscale ( http://web.expasy.org/protscale ) were used to predict the Physico-chemical properties and hydrophobic of amino acid residues in ATP7B wild-type and R778L mutation type protein, respectively. (beingmedicos.com)
Mutant R701W, which was found in a heterozygous very young patient with severe neurological problems, was unable to complement per se but did so in the presence of copper-glutathione or when the yeast copper ATPase Ccc2p was co-expressed, indicating that the protein was structurally able to bind copper but that metal loading involving the mammalian copper ATPase ATP7B was impaired. (uniroma3.it)
Mutation in ATP7B causes dysfunction of ATP7B protein and reduction in copper excretion into bile in hepatocytes and excess copper accumulation leads to liver injury. (ectrx.org)
Wilson disease is a rare genetic disorder caused by mutations in the gene encoding the ATP7B protein, which reduces the ability of the liver and other tissues to regulate copper levels, causing severe hepatic damage, neurologic symptoms and potentially death. (vivet-therapeutics.com)

This necessitated systematic characterization of the molecular consequences of distinct ATP7B missense mutations associated with WD. (ru.nl)
Classic evolutionary theories only consider the functional consequence of missense mutations, and the synonymous mutations are regarded as neutral sites and are used as "control group" to test the selection force on missense mutations [ 3 , 4 , 5 ]. (biomedcentral.com)

Meanwhile, synonymous mutations decreasing codon optimality slowed down translation, and were enriched in tumor suppressor genes. (biomedcentral.com)
Patients who suffer from the disease inherit the 2 ATP7B genes with mutations from each parent. (chennailiverfoundation.org)
While some people inherit these conditions from their parents or close relatives, others are born with abnormal changes (or mutations) in their genes. (xcode.life)

Wilson's disease is due to a mutation in the gene coding for a copper transporting ATPase, ATP7B . (blogspot.com)

Ferenci P. Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. (medlineplus.gov)
In an interview with HT Lifestyle, Dr Purshottam Vashistha, Consultant - Gastroenterology at Apollo Hospitals in Navi Mumbai, shared, "Wilson's Disease is caused by a genetic mutation that affects the body's ability to metabolize copper. (hindustantimes.com)
Genetic analysis of ATP7B in 102 south Indian families with Wilson disease. (cdc.gov)
Relationship between genetic mutations and clinical phenotypes in patients with Wilson disease. (cdc.gov)
Wilson's disease is caused by genetic mutations in the ATP7B gene which is responsible for the transportation of the dietary copper to the liver . (wikidoc.org)
Monogenic disorders, such as Huntington's disease, cystic fibrosis, thalassemia, and sickle cell anemia, are caused by single-gene mutations while multifactorial diseases such as cancer and diabetes resulted from an interplay between numerous genetic mutations and environmental conditions. (ubigene.us)

Postrigan' A.E., Zarubin A.A, Nikitina T.V., Bueverov A.O., Bogomolov P.O., Zakian S.M., Skryabin N.A. Generation of an induced pluripotent stem cell line ICGi030-A from a male patient with Wilson's disease carrying a frameshift mutation p.Lys1013fs and missense mutation p.H1069Q in the ATP7B gene // Stem Cell Research. (tnimc.ru)

Huster D, Hoppert M, Lutsenko S, Zinke J, Lehmann C, Mossner J, Berr F, Caca K. Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines. (medlineplus.gov)
The primary cause of copper toxicosis in Labrador Retrievers is a mutant form of ATP7B. (dogwellnet.com)
cDNA fragments coding for the N-terminal (ATP7B R778LN) and C-terminal (ATP7B R778LC) halves of mutant human ATP7B R778L (GenBank, NM_000053.3) were obtained by PCR amplification using the 'primer 1' for ATP7B R778LN, and 'primer 2' for ATP7B R778LC, respectively. (beingmedicos.com)
Then, successfully established ATP7B R778L mutant lentivirus constructs were utilized to infect HepG2 cells seeded in a 6-well plate. (beingmedicos.com)
Copper-dependent trafficking of Wilson disease mutant ATP7B proteins. (ijpediatrics.com)

Recently, molecular evidence showed that synonymous mutations actually have their functional impact. (biomedcentral.com)
Mutations in cancers likely alter a great number of molecular events. (ubigene.us)
Within these sets of mutations, we expect to observe loss-of-function mutations that turn-off normal molecular function. (ubigene.us)
that is, mutations that cause a molecular function to have deregulated activation when compared to normal function. (ubigene.us)

Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. (bvsalud.org)
First, we included mutations in the ATP7B gene that were registered in the Human Gene Mutation Database (HGMD) Professional, where 885 ATP7B variants were identified as pathogenic. (chronicliverdisease.org)
Many research studies revealed the correlation between ATP7B gene mutation and Wilson's disease. (wikidoc.org)
ATP7B gene mutation is found in the majority of the patients with Wilson's disease. (wikidoc.org)
Wilson's disease is caused by ATP7B gene mutation and impairement of copper transportation. (wikidoc.org)

Our previous and current studies have utilized a mouse model for Wilson's disease (Atp7b -/- mouse). (bcm.edu)
Wilson's disease results from mutations in the Atp7b transporter, which leads to excessive hepatic copper levels and progressive liver disease. (bcm.edu)
Wilson's disease patients and Atp7b -/- mice have profound mitochondria and nuclear ultrastructural changes that are likely due to copper induction of redox stress in the hepatocyte and develop spontaneous hepatic nodules between 10-16 months of age. (bcm.edu)
Our lab identified that excessive copper concentrations decreased metabolic nuclear receptor activity (FXR - farnesoid X receptor, HNF4a - hepatocyte nuclear factor, and LRH-1 - liver receptor homolog-1) in vivo, Atp7b -/- mice, and Wilson's disease patients. (bcm.edu)
Our current projects aim to understand the mechanisms driving metabolic and hepatocellular changes in Atp7b -/- mice and whether ligand activation of nuclear receptors lessens the hepatocellular dysfunction in Wilson's disease. (bcm.edu)
Wilson's disease is caused by a mutation of the ATP7B gene, which is responsible for metabolizing copper. (blogspot.com)
Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B. (9lib.net)
Estimate of the frequency of Wilson's disease in the US Caucasian population: a mutation analysis approach. (ijpediatrics.com)
In Wilson's disease, a mutation to the ATP7B gene causes a disruption in the excretion of copper into bile, resulting in copper accumulation in the liver. (naturopathicpediatrics.com)

Here, we review these new approaches, which comprise correction of ATP7B mutants and discovery of new compounds that circumvent ATP7B-deficiency, as well as cell and gene therapies. (unina.it)

Approximately one-third of Asians with Wilson disease have a mutation that replaces the amino acid arginine with the amino acid leucine at position 778 (written as Arg778Leu or R778L). (medlineplus.gov)
ATP7B R778L HepG2 cells were grown in DMEM supplemented with 10% fetal bovine serum, 2 mM L-Glutamine, and 2ug/ml puromycin (Invitrogen, Grand Island, NY, USA). (beingmedicos.com)
The final PCR products composed of ATP7B R778L and FLAG tag were cloned into the pLVX-CMV7-MCS-EF1a-Puro using a seamless cloning reaction system (Sangon Biotech, Shanghai, China) (Supplementary Fig. S1b ) and then validated by DNA sequencing. (beingmedicos.com)
The establishment of lentiviral constructs with ATP7B R778L mutation mainly included packaging, concentration, and purification. (beingmedicos.com)
HEK-293T cells were transfected with plasmid vectors carrying ATP7B R778L and packaging plasmids pCMV-dR8.9 (Addgene, Cambridge, America) and pCMV-VSV-G (Addgene, Cambridge, America). (beingmedicos.com)
The stable HepG2 cells overexpressing R778L ATP7B were obtained by continuous screening with 2 µg/mL puromycin for 2 weeks and checked by PCR and western blot analyses. (beingmedicos.com)

2) Investigation or experimental verification of a particular or a few synonymous mutation(s) related to particular phenotype. (biomedcentral.com)
Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease. (cdc.gov)
Vrabelova S, Letocha O, Borsky M, Kozak L. Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease. (ijpediatrics.com)

The occurrence of these disorders indicates the fundamental importance of atp7a and atp7b. (web.app)

The carrier frequency of ATP7B variants and the prevalence of WD in the Japanese population have not been reported using multiple databases. (chronicliverdisease.org)
This is the first study to report the carrier frequency of ATP7B variants and the prevalence of WD in Japan using multiple databases. (chronicliverdisease.org)

Notably, R701W exerted a dominant negative effect on wild type, and it induced the subcellular relocalization of ATP7B. (uniroma3.it)

Four distinct mutations exhibited residual copper export capacity, whereas other mutations resulted in complete disruption of copper export by ATP7B. (ru.nl)

In the Costa Rican population, more than 60 percent of affected individuals have a mutation that replaces the amino acid aspartic acid with the amino acid serine at position 1270 (written as Asp1270Ser or D1270S). (medlineplus.gov)
These types of mutations usually result in symptoms that are more severe than those caused by mutations that change a single amino acid. (medlineplus.gov)
By definition, synonymous mutations are those mutations that do not change amino acids, and they usually take place at the third codon positions [ 1 , 2 ]. (biomedcentral.com)

Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin. (ru.nl)
Researchers have identified more than 250 ATP7B gene mutations that cause Wilson disease. (medlineplus.gov)
Wilson disease is caused by an inherited change or abnormality (mutation) in the ATP7B gene. (bjsph.org)
Wilson disease patient with rare heterozygous mutations in ATP7B accompanied by distinctive nocturnal enuresis: A case report. (cdc.gov)
Wilson's unwellness is caused by a mutation within the Wilson disease super molecule (ATP7B) factor. (scitechnol.com)
Mutations in atp7b lead to wilson disease, which is characterized by a predominantly hepatic copper. (web.app)

Mutations lead to copper transporter dysfunction with subsequent copper deposition in the liver and other organs. (biomedcentral.com)

Evolutionary study indicated that synonymous mutations in oncogenes were also suppressed due to undetermined selection pressure [ 25 ]. (biomedcentral.com)
The ATP7B evolutionary conservation scores were computed via the ConSurf webserver ( http://consurf.tau.ac.il/38 ). (beingmedicos.com)

The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. (bvsalud.org)

Given the functional impact of synonymous mutations, there is no reason to exclude these mutations from the studies related to human diseases including cancer. (biomedcentral.com)
The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. (bvsalud.org)

Of the 885 variants of ATP7B, 7 and 12 missense and nonsense variants, zero and three splicing variants, and zero and two small deletions were found in the HGVD and in jMorp, respectively. (chronicliverdisease.org)

In addition, it is possible there are breed-specific forms of these diseases where the mutations responsible have not yet been identified. (dogwellnet.com)

This mutation helps minimize the accumulation of copper in the liver, and is X-linked Recessive. (dogwellnet.com)

For example, genome-wide analysis revealed that a part of synonymous mutations could affect mRNA splicing and might contribute to cancer progression [ 24 ]. (biomedcentral.com)
The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. (bvsalud.org)

Identification of ATP7B gene variant by combined use of Sanger sequencing, array CGH and quantitative PCR]. (cdc.gov)

We profiled the mutation spectrum and examined the effect of synonymous mutations on translational velocity. (biomedcentral.com)

Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. (bvsalud.org)

These synonymous mutations significantly contributed to the translational changes in tumor samples compared to normal samples. (biomedcentral.com)
Germline mutations in this gene may be associated with tumor predisposition syndrome (TPDS), which involves increased risk of cancers including malignant mesothelioma, uveal melanoma and cutaneous melanoma. (utsouthwestern.edu)

There are already a bunch of studies reporting the disease-related synonymous mutations. (biomedcentral.com)
Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. (bvsalud.org)
Menkes disease is an xlinked lethal multi system disorder caused by disturbances of copper distribution in different tissues due to mutation of p atpase7 gene. (web.app)

Finally, we expect to observe many mutations that do not participate in neoplastic development and progression. (ubigene.us)

The possibility to reverse the deleterious effects of some aceruloplasminemia mutations may disclose new possible therapeutic strategies. (uniroma3.it)

1) Bioinformatic analyses studying the global patterns of the collective effect of synonymous mutations. (biomedcentral.com)

However, synonymous mutations will change the codon optimality, resulting in altered translational velocity. (biomedcentral.com)

Automatically, they have been regarded as neutral events and are ignored in the mutation-based cancer studies. (biomedcentral.com)
Synonymous mutations should no longer be ignored in the genome-wide studies. (biomedcentral.com)

Anatomy13

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Wilson Disease6

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