Disease relevance of ETHE1

• The gene had previously been known as "HSCO" (for hepatoma subtracted clone one) [1].
• The role of methionine in ethylmalonic encephalopathy with petechiae [2].
• This case suggests that ethylmalonic aciduria is not a constant biochemical marker of ethylmalonic encephalopathy and that its normal excretion outside of metabolic decompensation episodes does not exclude this metabolic disease [3].
• Ethylmalonic encephalopathy (EE), an organic aciduria of unknown etiology characterized by developmental delay, hypotonia, and vascular instability associated with lactic acidemia and urinary excretion of ethylmalonic acid (EMA) and methylsuccinic acid (MSA), has been described in 11 patients [4].
• We assessed the radiosensitivity of human HSCO oropharyngeal squamous carcinoma cells in the presence of paracrine factors produced by human HECV umbilical vein endothelial cells [5].

High impact information on ETHE1

• Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels [1].
• A child is reported presenting with a clinical picture suggestive of genetic connective tissue disorders (vascular fragility, articular hyperlaxity, delayed motor development, and normal cognitive development), an absence of pathological ethylmalonic acid excretion during inter-critical phases and a homozygous R163W mutation in the ETHE1 gene [3].
• Central nervous system malformations in ethylmalonic encephalopathy [6].
• Ethylmalonic encephalopathy, an organic aciduria of unknown pathogenesis, has not been reported previously in association with brain or spinal cord malformations [6].
• Mutation analysis of copper transporter genes in patients with ethylmalonic encephalopathy, mitochondriopathies and copper deficiency phenotypes [7].

Biological context of ETHE1

• Here we report identification of HSCO that binds to NF-kappa B and inhibits apoptosis [8].
• Frameshift, stop, splice site, and missense mutations of ETHE1 were detected in all the typical EE patients analysed [9].
• Mutations in ETHE1, a gene located at chromosome 19q13, have recently been identified in patients affected by ethylmalonic encephalopathy (EE) [9].

Associations of ETHE1 with chemical compounds

• Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise from abnormal isoleucine metabolism [4].

Regulatory relationships of ETHE1

• These results suggest that overexpression of HSCO suppresses p53-induced apoptosis by preventing nuclear localization of NF-kappa B during signaling and thus contributes to hepatocarcinogenesis [8].

Other interactions of ETHE1

• The metallo-beta-lactamase family consensus sequence in HSCO is important for its effect on p53 deacetylation [10].

Analytical, diagnostic and therapeutic context of ETHE1

• Western blot analysis of the ETHE1 protein indicated that some of the missense mutations are associated with the presence of the protein, suggesting that the corresponding wild type amino acid residues have a catalytic function [9].

References