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Available structures
PDBOrtholog search: PDBe RCSB
AliasesETHE1, HSCO, YF13H12, persulfide dioxygenase
External IDsMGI: 1913321 HomoloGene: 8622 GeneCards: ETHE1
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for ETHE1
Genomic location for ETHE1
Band19q13.31Start43,506,719 bp[1]
End43,527,244 bp[1]
RNA expression pattern
PBB GE ETHE1 204034 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 19: 43.51 – 43.53 MbChr 7: 24.59 – 24.61 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Protein ETHE1, mitochondrial, also known as "ethylmalonic encephalopathy 1 protein" and "per sulfide dioxygenase", is a protein that in humans is encoded by the ETHE1 gene located on chromosome 19.[5]


The human ETHE1 gene consists of 7 exons and encodes for a protein that is approximately 27 kDa in size.


This gene encodes a protein that is expressed in the thyroid.[5]

The ETHE1 protein is thought to localize primarily to the mitochondrial matrix [6][7] and functions as a sulfur dioxygenase. Sulfur deoxygenates are proteins that function in sulfur metabolism. The ETHE1 protein is thought to catalyze the following reaction:

sulfur + O2 + H2O sulfite + 2 H+ (overall reaction)
(1a) glutathione + sulfur S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)
(1b) S-sulfanylglutathione + O2 + H2O glutathione + sulfite + 2 H+[6]

and requires iron[8] and possibly glutathione[8] as cofactors. The physiological substrate of ETHE1 is thought to be glutathione persulfide,[8] an intermediate metabolite involved in hydrogen sulfide degradation.

Clinical significance[edit]

Mutations in ETHE1 gene are thought to cause ethylmalonic encephalopathy,[7][9] a rare inborn error of metabolism. Patients carrying ETHE1 mutations have been found to exhibit lower activity of ETHE1 and affinity for the ETHE1 substrate.[8] Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.[6] Decrease in sulfide dioxygenase activity results in abnormal catabolism of hydrogen sulfide, an gas-phase signaling molecule in the central nervous system,[8] whose accumulation is thought to inhibit cytochrome c oxidase activity in the respiratory chain of the mitochondrion.[6] However, other metabolic pathways may also be involved that could exert a modulatory effect on hydrogen sulfide toxicity.[10]


ETHE1 has been shown to interact with RELA.[11]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000105755 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064254 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b "Entrez Gene: ETHE1 ethylmalonic encephalopathy 1".
  6. ^ a b c d Tiranti V, Viscomi C, Hildebrandt T, Di Meo I, Mineri R, Tiveron C, Levitt MD, Prelle A, Fagiolari G, Rimoldi M, Zeviani M (2009). "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy". Nat. Med. 15 (2): 200–5. doi:10.1038/nm.1907. PMID 19136963.
  7. ^ a b Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Garcia-Silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-Vici C, Garavaglia B, Gasparini P, Zeviani M (2004). "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein". Am. J. Hum. Genet. 74 (2): 239–52. doi:10.1086/381653. PMC 1181922. PMID 14732903.
  8. ^ a b c d e Kabil O, Banerjee R (2012). "Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism". J. Biol. Chem. 287 (53): 44561–7. doi:10.1074/jbc.M112.407411. PMC 3531769. PMID 23144459.
  9. ^ "Encephalopathy, Ethylmalonic". Johns Hopkins University. Retrieved 2012-05-12.
  10. ^ Barth M, Ottolenghi C, Hubert L, Chrétien D, Serre V, Gobin S, Romano S, Vassault A, Sefiani A, Ricquier D, Boddaert N, Brivet M, de Keyzer Y, Munnich A, Duran M, Rabier D, Valayannopoulos V, de Lonlay P (2010). "Multiple sources of metabolic disturbance in ETHE1-related ethylmalonic encephalopathy". J. Inherit. Metab. Dis. 33 Suppl 3: S443–53. doi:10.1007/s10545-010-9227-y. PMID 20978941.
  11. ^ Higashitsuji H, Higashitsuji H, Nagao T, Nonoguchi K, Fujii S, Itoh K, Fujita J (Oct 2002). "A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis". Cancer Cell. 2 (4): 335–46. doi:10.1016/S1535-6108(02)00152-6. PMID 12398897.

Further reading[edit]