This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and per... See more...

Aliases for ETHE1 Gene

Aliases for ETHE1 Gene

  • ETHE1 Persulfide Dioxygenase 2 3 5
  • Persulfide Dioxygenase ETHE1, Mitochondrial 3 4
  • Hepatoma Subtracted Clone One Protein 3 4
  • Ethylmalonic Encephalopathy 1 2 3
  • Sulfur Dioxygenase ETHE1 3 4
  • HSCO 3 4
  • Ethylmalonic Encephalopathy Protein 1 4
  • Protein ETHE1, Mitochondrial 3
  • EC 1.13.11.18 4
  • EC 3.1.2.6 52
  • YF13H12 3

External Ids for ETHE1 Gene

Previous GeneCards Identifiers for ETHE1 Gene

  • GC19M048702
  • GC19M044010
  • GC19M040440

Summaries for ETHE1 Gene

Entrez Gene Summary for ETHE1 Gene

  • This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and peripheral vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

GeneCards Summary for ETHE1 Gene

ETHE1 (ETHE1 Persulfide Dioxygenase) is a Protein Coding gene. Diseases associated with ETHE1 include Encephalopathy, Ethylmalonic and Encephalopathy. Among its related pathways are Metabolism and Sulfur amino acid metabolism. Gene Ontology (GO) annotations related to this gene include iron ion binding and sulfur dioxygenase activity. An important paralog of this gene is PNKD.

UniProtKB/Swiss-Prot Summary for ETHE1 Gene

  • Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase. First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (PubMed:12398897).

Gene Wiki entry for ETHE1 Gene

Additional gene information for ETHE1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ETHE1 Gene

Genomics for ETHE1 Gene

GeneHancer (GH) Regulatory Elements for ETHE1 Gene

Promoters and enhancers for ETHE1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ETHE1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ETHE1

Top Transcription factor binding sites by QIAGEN in the ETHE1 gene promoter:
  • AP-2alpha
  • AP-2alphaA
  • AP-2beta
  • AP-2gamma
  • AREB6
  • p53
  • Pax-4a
  • TBP
  • TFIID
  • Zic1

Genomic Locations for ETHE1 Gene

Genomic Locations for ETHE1 Gene
chr19:43,506,719-43,527,244
(GRCh38/hg38)
Size:
20,526 bases
Orientation:
Minus strand
chr19:44,010,871-44,031,396
(GRCh37/hg19)
Size:
20,526 bases
Orientation:
Minus strand

Genomic View for ETHE1 Gene

Genes around ETHE1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ETHE1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ETHE1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ETHE1 Gene

Proteins for ETHE1 Gene

  • Protein details for ETHE1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95571-ETHE1_HUMAN
    Recommended name:
    Persulfide dioxygenase ETHE1, mitochondrial
    Protein Accession:
    O95571
    Secondary Accessions:
    • Q96HR0
    • Q9H001

    Protein attributes for ETHE1 Gene

    Size:
    254 amino acids
    Molecular mass:
    27873 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Quaternary structure:
    • Homodimer (PubMed:25596185). Monomer (PubMed:23144459). Interacts with TST (PubMed:19136963). May interact with RELA (PubMed:12398897).
    SequenceCaution:
    • Sequence=AAG09063.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ETHE1 Gene

neXtProt entry for ETHE1 Gene

Selected DME Specific Peptides for ETHE1 Gene

O95571:
  • LIRGCGRTDFQ
  • MAFTGDA

Post-translational modifications for ETHE1 Gene

  • Ubiquitination at Lys66
  • Modification sites at PhosphoSitePlus

Domains & Families for ETHE1 Gene

Gene Families for ETHE1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for ETHE1 Gene

Suggested Antigen Peptide Sequences for ETHE1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ96390, highly similar to Homo sapiens protein expressed in thyroid (YF13H12), mRNA (B2RCZ7_HUMAN)
  • Hepatoma subtracted clone one protein (ETHE1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95571

UniProtKB/Swiss-Prot:

ETHE1_HUMAN :
  • Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.
Family:
  • Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.
genes like me logo Genes that share domains with ETHE1: view

Function for ETHE1 Gene

Molecular function for ETHE1 Gene

UniProtKB/Swiss-Prot Function:
Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase. First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (PubMed:12398897).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O2 + S-sulfanylglutathione = glutathione + 2 H(+) + sulfite; Xref=Rhea:RHEA:12981, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17359, ChEBI:CHEBI:57925, ChEBI:CHEBI:58905; EC=1.13.11.18; Evidence={ECO:0000269 PubMed:19136963, ECO:0000269 PubMed:23144459, ECO:0000269 PubMed:25596185};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Glutathione increases enzyme activity.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.34 mM for glutathione persulfide (GSSH) {ECO:0000269 PubMed:23144459}; Vmax=113 umol/min/mg enzyme (in the presence of equimolar amounts of GSSH and GSH and at 22 degrees Celsius) {ECO:0000269 PubMed:23144459};

Enzyme Numbers (IUBMB) for ETHE1 Gene

Phenotypes From GWAS Catalog for ETHE1 Gene

Gene Ontology (GO) - Molecular Function for ETHE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005506 iron ion binding IDA 23144459
GO:0016491 oxidoreductase activity IEA --
GO:0016788 hydrolase activity, acting on ester bonds IBA 21873635
GO:0046872 metal ion binding IEA --
GO:0050313 sulfur dioxygenase activity IDA,IBA 23144459
genes like me logo Genes that share ontologies with ETHE1: view
genes like me logo Genes that share phenotypes with ETHE1: view

Human Phenotype Ontology for ETHE1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ETHE1 Gene

MGI Knock Outs for ETHE1:
  • Ethe1 Ethe1<tm1.1Zev>
  • Ethe1 Ethe1<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Clone Products

No data available for miRNA , Transcription Factor Targets and HOMER Transcription for ETHE1 Gene

Localization for ETHE1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ETHE1 Gene

Cytoplasm. Nucleus. Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ETHE1 gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ETHE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA --
GO:0005739 mitochondrion IDA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with ETHE1: view

Pathways & Interactions for ETHE1 Gene

genes like me logo Genes that share pathways with ETHE1: view

Gene Ontology (GO) - Biological Process for ETHE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006749 glutathione metabolic process IDA 23144459
GO:0055114 oxidation-reduction process IEA --
GO:0070221 sulfide oxidation, using sulfide:quinone oxidoreductase TAS --
GO:0070813 hydrogen sulfide metabolic process IDA 23144459
genes like me logo Genes that share ontologies with ETHE1: view

No data available for SIGNOR curated interactions for ETHE1 Gene

Drugs & Compounds for ETHE1 Gene

(1) Additional Compounds for ETHE1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ETHE1: view

Transcripts for ETHE1 Gene

mRNA/cDNA for ETHE1 Gene

4 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ETHE1 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b
SP1: - -
SP2: - - -
SP3: - -
SP4:
SP5: -

Relevant External Links for ETHE1 Gene

GeneLoc Exon Structure for
ETHE1

Expression for ETHE1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ETHE1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ETHE1 Gene

This gene is overexpressed in Colon - Transverse (x8.6).

Protein differential expression in normal tissues from HIPED for ETHE1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ETHE1 Gene



Protein tissue co-expression partners for ETHE1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ETHE1

SOURCE GeneReport for Unigene cluster for ETHE1 Gene:

Hs.7486

mRNA Expression by UniProt/SwissProt for ETHE1 Gene:

O95571-ETHE1_HUMAN
Tissue specificity: Ubiquitously expressed.

Evidence on tissue expression from TISSUES for ETHE1 Gene

  • Liver(4.3)
  • Eye(4.2)
  • Intestine(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ETHE1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cerebellum
  • eye
  • head
Abdomen:
  • intestine
  • large intestine
  • small intestine
Pelvis:
  • anus
  • rectum
General:
  • blood
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with ETHE1: view

Orthologs for ETHE1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for ETHE1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ETHE1 31 30
  • 99.56 (n)
OneToOne
dog
(Canis familiaris)
Mammalia ETHE1 31 30
  • 90.87 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ETHE1 31 30
  • 89.02 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ethe1 17 31 30
  • 84.52 (n)
rat
(Rattus norvegicus)
Mammalia Ethe1 30
  • 83.73 (n)
chicken
(Gallus gallus)
Aves ETHE1 31 30
  • 64.26 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ETHE1 31
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ethe1 30
  • 65.33 (n)
zebrafish
(Danio rerio)
Actinopterygii ethe1 31 30
  • 63.73 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG30022 31 30
  • 58.76 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003337 30
  • 57.59 (n)
worm
(Caenorhabditis elegans)
Secernentea ethe-1 31 30
  • 53.65 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GLO2 31
  • 19 (a)
ManyToMany
GLO4 31
  • 18 (a)
ManyToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons GLY3 30
  • 53.74 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.9394 30
soybean
(Glycine max)
eudicotyledons Gma.6593 30
rice
(Oryza sativa)
Liliopsida Os01g0667200 30
  • 57.88 (n)
barley
(Hordeum vulgare)
Liliopsida Hv.2764 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 56 (a)
OneToMany
CSA.3242 31
  • 49 (a)
OneToMany
Species where no ortholog for ETHE1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ETHE1 Gene

ENSEMBL:
Gene Tree for ETHE1 (if available)
TreeFam:
Gene Tree for ETHE1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ETHE1: view image

Paralogs for ETHE1 Gene

Paralogs for ETHE1 Gene

genes like me logo Genes that share paralogs with ETHE1: view

Variants for ETHE1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ETHE1 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
640004 Pathogenic: Ethylmalonic encephalopathy 43,526,281(-) G/A NONSENSE,INTRON_VARIANT
658833 Uncertain Significance: Ethylmalonic encephalopathy 43,506,854(-) G/A MISSENSE_VARIANT
671157 Benign: not provided 43,511,173(-) A/C INTRON_VARIANT
671647 Benign: not provided 43,507,763(-) T/C INTRON_VARIANT
673475 Likely Benign: not provided 43,507,856(-) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for ETHE1 Gene

Structural Variations from Database of Genomic Variants (DGV) for ETHE1 Gene

Variant ID Type Subtype PubMed ID
dgv3603n100 CNV gain 25217958
esv1297424 CNV insertion 17803354
esv2584150 CNV insertion 19546169
esv2661743 CNV deletion 23128226
esv2762041 CNV loss 21179565
nsv1056785 CNV gain 25217958
nsv1057657 CNV gain 25217958
nsv137943 CNV deletion 16902084
nsv513529 CNV insertion 21212237

Variation tolerance for ETHE1 Gene

Residual Variation Intolerance Score: 36.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.43; 42.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ETHE1 Gene

Human Gene Mutation Database (HGMD)
ETHE1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ETHE1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ETHE1 Gene

Disorders for ETHE1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for ETHE1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search ETHE1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ETHE1_HUMAN
  • Ethylmalonic encephalopathy (EE) [MIM:602473]: Autosomal recessive disorder characterized by neurodevelopmental delay and regression, recurrent petechiae, acrocyanosis, diarrhea, leading to death in the first decade of life. It is also associated with persistent lactic acidemia and ethylmalonic and methylsuccinic aciduria. {ECO:0000269 PubMed:14732903, ECO:0000269 PubMed:18593870, ECO:0000269 PubMed:23144459}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for ETHE1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with ETHE1: view

No data available for Genatlas for ETHE1 Gene

Publications for ETHE1 Gene

  1. Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. (PMID: 19136963) Tiranti V … Zeviani M (Nature medicine 2009) 2 3 4 54
  2. Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy. (PMID: 18593870) Mineri R … Tiranti V (Journal of medical genetics 2008) 3 4 23 54
  3. Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. (PMID: 14732903) Tiranti V … Zeviani M (American journal of human genetics 2004) 3 4 23 54
  4. A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis. (PMID: 12398897) Higashitsuji H … Fujita J (Cancer cell 2002) 3 4 23 54
  5. Characterization of patient mutations in human persulfide dioxygenase (ETHE1) involved in H2S catabolism. (PMID: 23144459) Kabil O … Banerjee R (The Journal of biological chemistry 2012) 3 4 54

Products for ETHE1 Gene

Sources for ETHE1 Gene