DCTN4, dynactin subunit 4, 51164

N. diseases: 253; N. variants: 4
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0010674
Disease: Cystic Fibrosis
Cystic Fibrosis 		0.540 GeneticVariation disease BEFREE Our observations reinforce that DCTN4 missense variants, especially p.Tyr263Cys, may be involved in the pathogenesis of CPA in male CF. 25763772 2016
CUI: C0010674
Disease: Cystic Fibrosis
Cystic Fibrosis 		0.540 GeneticVariation disease BEFREE For a fixed sample size, sequencing of individuals sampled from the tails of a phenotype distribution (i.e., extreme phenotypes design) maximizes power and this approach was recently validated empirically with the discovery of variants in DCTN4 that influence the natural history of P. aeruginosa airway infection in persons with cystic fibrosis (CF; MIM219700). 26047157 2015
CUI: C0010674
Disease: Cystic Fibrosis
Cystic Fibrosis 		0.540 GeneticVariation disease BEFREE As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis. 22772370 2012
CUI: C0206698
Disease: Cholangiocarcinoma
Cholangiocarcinoma 		0.120 GeneticVariation disease GWASCAT Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis. 28779025 2018
CUI: C0002736
Disease: Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 		0.100 GeneticVariation disease BEFREE SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. 25114083 2015
CUI: C0002736
Disease: Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 		0.100 GeneticVariation disease BEFREE Previously, two ALS-FTLD-associated p62 mutant proteins within the Keap1 interacting region (KIR) of p62 were found to be associated with decreased Keap1-p62 binding and Nrf2 activation. 30954537 2019
CUI: C0002736
Disease: Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 		0.100 GeneticVariation disease BEFREE Here we consider how knowledge of the impact of PDB-associated SQSTM1 mutations (several of which are now known to be relevant for ALS/FTLD) on these pathways, as well as the locations of the mutations within the p62 primary sequence, may provide new insights into ALS/FTLD disease mechanisms. 24486447 2014
CUI: C0002736
Disease: Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 		0.100 GeneticVariation disease BEFREE Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. 23303844 2013
CUI: C0002736
Disease: Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 		0.100 GeneticVariation disease BEFREE Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS). 23812289 2013
CUI: C0002736
Disease: Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis 		0.100 GeneticVariation disease BEFREE These mutations that are located in the ubiquitin-associated domain (UBA domain) of the p62 protein have already been described in Paget's disease and ALS patients carrying these mutations had both concomitant Paget's disease. 23417734 2013
CUI: C0008313
Disease: Cholangitis, Sclerosing
Cholangitis, Sclerosing 		0.100 GeneticVariation disease GWASCAT Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis. 28779025 2018
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE To further clarify the functional impact of p62 mutations associated with PDB, we assessed the effect of p62 mutation (a novel mutation: K378X, and previously reported mutations: P392L and E396X) on RANK-induced NF-kappaB activation and compared this with the effect of wildtype p62. 16813535 2006
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE Further, mutations affecting the UBA domain (ubiquitin-associated domain) of p62 are commonly found in patients with the skeletal disorder PDB (Paget's disease of bone). 18481983 2008
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE The condition has a strong genetic component, with mutations affecting the SQSTM1 gene that encodes the p62 protein often found in PDB patients, although environmental factors also play an important role in disease aetiology. 19858527 2010
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE To further clarify the mechanisms by which these mutations predispose to PDB, we have extended these analyses to study the ubiquitin-binding properties of the PDB-causing mutations in the context of the full-length p62 protein. 15765181 2005
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE Here we consider how knowledge of the impact of PDB-associated SQSTM1 mutations (several of which are now known to be relevant for ALS/FTLD) on these pathways, as well as the locations of the mutations within the p62 primary sequence, may provide new insights into ALS/FTLD disease mechanisms. 24486447 2014
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE These mutations that are located in the ubiquitin-associated domain (UBA domain) of the p62 protein have already been described in Paget's disease and ALS patients carrying these mutations had both concomitant Paget's disease. 23417734 2013
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE These results indicate that this PDB-associated p62 mutation is not sufficient to induce PDB and suggest that additional factors acting together with p62 mutation are necessary for the development of PDB in vivo. 18765443 2008
CUI: C0029401
Disease: Osteitis Deformans
Osteitis Deformans 		0.100 GeneticVariation disease BEFREE Functional analyses of PDB (Paget's disease of bone)-associated mutants of the p62 [also known as SQSTM1 (sequestosome 1)] signalling adaptor protein represent an interesting paradigm for understanding not only the disease mechanism in this skeletal disorder, but also the critical determinants of ubiquitin recognition by an ubiquitin-binding protein. 17052185 2006
CUI: C0152013
Disease: Adenocarcinoma of lung (disorder)
Adenocarcinoma of lung (disorder) 		0.100 GeneticVariation disease GWASCAT Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. 28604730 2017
CUI: C0030567
Disease: Parkinson Disease
Parkinson Disease 		0.070 GeneticVariation disease BEFREE Furthermore, examination of p62 by immunohistochemistry (IH) recapitulated a distinct signature for G2019S PD. 30055128 2018
CUI: C0751072
Disease: Frontotemporal Lobar Degeneration
Frontotemporal Lobar Degeneration 		0.070 GeneticVariation disease BEFREE Here we report that a non-KIR domain FTLD-associated variant of p62 (p.R110C), affecting a residue close to the N-terminal PB1 oligomerisation domain, also reduces Keap1-p62 binding in cellulo and thereby reduces Nrf2 activity in reporter assays. 30954537 2019
CUI: C0338451
Disease: Frontotemporal dementia
Frontotemporal dementia 		0.050 GeneticVariation disease BEFREE An FTD-linked p62 D329G polymorphism and a rare D329H variant could not be proteolyzed by caspase-8, and these noncleavable variants failed to activate mTORC1, thereby revealing the detrimental effect of these mutations. 30514811 2018
CUI: C0001418
Disease: Adenocarcinoma
Adenocarcinoma 		0.040 GeneticVariation group BEFREE Moreover, p62 and VPRBP were associated with poor prognosis in lung ADC (adenocarcinoma) (p62, P=0.019; VPRBP, P=0.005). 22963397 2013
CUI: C0027819
Disease: Neuroblastoma
Neuroblastoma 		0.040 GeneticVariation disease BEFREE In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). 28490746 2017