ETHE1 (ETHE1 persulfide dioxygenase)

Gene

• Entrez ID: 23474
• Gene name: ETHE1 persulfide dioxygenase
• Gene symbol: ETHE1
• Synonyms (NCBI Gene): HSCO, YF13H12
• Chromosome: 19
• Chromosome location: 19q13.31
• Summary: 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 thi

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28940289	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs119103249	C>A,T	Pathogenic	5 prime UTR variant, initiator codon variant, missense variant
rs182983506	A>G	Pathogenic	Missense variant, 5 prime UTR variant, intron variant, coding sequence variant
rs368778231	G>A	Pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant, intron variant
rs387906987	A>C	Pathogenic	Coding sequence variant, missense variant
rs745656120	C>T	Pathogenic	Coding sequence variant, missense variant
rs749803238	G>A,T	Pathogenic	5 prime UTR variant, stop gained, coding sequence variant, missense variant
rs756235299	T>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs761661864	A>C	Likely-pathogenic	Splice donor variant
rs761827730	CT>-	Pathogenic	Coding sequence variant, intron variant, 5 prime UTR variant, frameshift variant
rs763799125	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs768669208	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs769259233	C>T	Pathogenic	Intron variant
rs863223955	->T	Pathogenic	Stop gained, frameshift variant, intron variant, coding sequence variant, initiator codon variant
rs863223956	TG>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs935855792	C>A,G,T	Likely-pathogenic, pathogenic	Splice donor variant
rs1211555765	CGGGG>-,CGGGGCGGGG	Pathogenic	Upstream transcript variant
rs1268640442	G>C,T	Pathogenic	Coding sequence variant, missense variant
rs1284200516	T>C	Pathogenic	Coding sequence variant, missense variant
rs1317633085	G>A	Pathogenic	Missense variant, coding sequence variant
rs1555761934	->C	Pathogenic	Frameshift variant, coding sequence variant
rs1555762070	->G	Pathogenic-likely-pathogenic	Frameshift variant, coding sequence variant
rs1555762722	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555762753	CCATGCTGTGG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555765481	T>-	Pathogenic	Intron variant, coding sequence variant, frameshift variant
rs1555765524	C>A	Likely-pathogenic	Intron variant, splice donor variant
rs1555765528	->T	Pathogenic	Intron variant, coding sequence variant, frameshift variant, initiator codon variant
rs1555765564	T>C	Pathogenic	Intron variant, coding sequence variant, 5 prime UTR variant, missense variant
rs1555765689	G>-	Pathogenic	Frameshift variant, coding sequence variant, 5 prime UTR variant
rs1555765701	G>A	Pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant
rs1600019095	G>A	Pathogenic	Stop gained, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2222210	hsa-miR-1321	CLIP-seq
MIRT2222211	hsa-miR-3153	CLIP-seq
MIRT2222212	hsa-miR-3162-5p	CLIP-seq
MIRT2222213	hsa-miR-4300	CLIP-seq
MIRT2222214	hsa-miR-4317	CLIP-seq
MIRT2222215	hsa-miR-4428	CLIP-seq
MIRT2222216	hsa-miR-4668-5p	CLIP-seq
MIRT2222217	hsa-miR-4685-5p	CLIP-seq
MIRT2222218	hsa-miR-4739	CLIP-seq
MIRT2222219	hsa-miR-4746-3p	CLIP-seq
MIRT2222220	hsa-miR-4756-5p	CLIP-seq
MIRT2222221	hsa-miR-616	CLIP-seq
MIRT2222222	hsa-miR-920	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005506	Function	Iron ion binding	IDA	23144459
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006749	Process	Glutathione metabolic process	IBA
GO:0006749	Process	Glutathione metabolic process	IDA	23144459
GO:0006749	Process	Glutathione metabolic process	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0042802	Function	Identical protein binding	IPI	32296183
GO:0046872	Function	Metal ion binding	IEA
GO:0050313	Function	Sulfur dioxygenase activity	IBA
GO:0050313	Function	Sulfur dioxygenase activity	IDA	23144459
GO:0050313	Function	Sulfur dioxygenase activity	IEA
GO:0051213	Function	Dioxygenase activity	IEA
GO:0070813	Process	Hydrogen sulfide metabolic process	IBA
GO:0070813	Process	Hydrogen sulfide metabolic process	IDA	23144459

Other IDs

• MIM: 608451
• HGNC: 23287
• e!Ensembl: ENSG00000105755

Protein

• UniProt ID: O95571
• Protein name: Persulfide dioxygenase ETHE1, mitochondrial (EC 1.13.11.18) (Ethylmalonic encephalopathy protein 1) (Hepatoma subtracted clone one protein) (Sulfur dioxygenase ETHE1)
• Protein 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 cata
• PDB: 4CHL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00753	Lactamase_B	31 → 195	Metallo-beta-lactamase superfamily	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed. {ECO:0000269|PubMed:14732903}.
• Sequence:

  MAEAVLRVARRQLSQRGGSGAPILLRQMFEPVSCTFTYLLGDRESREAVLIDPVLETAPR
  DAQLIKELGLRLLYAVNTHCHADHITGSGLLRSLLPGCQSVISRLSGAQADLHIEDGDSI
  RFGRFALETRASPGHTPGCVTFVLNDHSMAFTGDALLIRGCGRTDFQQGCAKTLYHSVHE
  KIFTLPGDCLIYPAHDYHGFTVSTVEEERTLNPRLTLSCEEFVKIMGNLNLPKPQQIDFA
  VPANMRCGVQTPTA

• Sequence length: 254

Pathways

KEGG:

Sulfur metabolism
Metabolic pathways

Reactome:

Sulfide oxidation to sulfate

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the nervous system	Likely pathogenic	rs1555762722	RCV001814171	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ethylmalonic encephalopathy	Likely pathogenic; Pathogenic	rs2146021370, rs2145979349, rs2145977281, rs863223954, rs2145977394, rs2145984865, rs2146018812, rs2146019063, rs2146019689, rs28940289, rs119103249, rs2513603665, rs2513598932, rs1470124674, rs2513631545, rs1487930609, rs2513631693, rs2513609504, rs761661864, rs745656120, rs863223955, rs1284200516, rs370880966, rs2513609529, rs2513629634, rs2513631599, rs2513603652, rs2513631669, rs2513609859, rs1236038385, rs763799125, rs2513605883, rs2513630394, rs2513629289, rs1417306550, rs2513630522, rs1210404401, rs2513609510, rs2513631762, rs2513609656, rs761827730, rs2513629589, rs2513631822, rs2513631633, rs2513629530, rs2513609768, rs2513609434, rs2513609430, rs2513631654, rs1972245042, rs1972246084, rs387906987, rs935855792, rs756235299, rs1555762722, rs769259233, rs1555765701, rs1555765689, rs368778231, rs1555762753, rs1555762070, rs1555761934, rs1555765524, rs749803238, rs1600019095, rs1255836046	RCV001385547 RCV001989465 RCV001923044 RCV002000629 RCV001874236 RCV001883579 RCV001920091 RCV002007524 RCV001963246 RCV000002407 RCV000002408 RCV002509828 RCV002463984 RCV003079234 RCV003118677 RCV002658079 RCV002643327 RCV002843064 RCV002921945 RCV001377167 RCV000276936 RCV001272531 RCV003038856 RCV003145014 RCV003338213 RCV003467947 RCV003460030 RCV003460031 RCV003460032 RCV003460033 RCV003467948 RCV003476399 RCV003467949 RCV003467950 RCV003460034 RCV003467951 RCV003498076 RCV003498998 RCV003499018 RCV003499913 RCV003498294 RCV003604027 RCV003604638 RCV003604501 RCV003604771 RCV003605022 RCV003602914 RCV003822200 RCV004576418 RCV004576419 RCV004576420 RCV004586319 RCV004595306 RCV000023703 RCV000495931 RCV000501489 RCV000503577 RCV000578436 RCV000578329 RCV000589263 RCV000587866 RCV000598827 RCV000599262 RCV000598926 RCV000598580 RCV000599476 RCV000598891 RCV000598849 RCV000599349 RCV000644795 RCV000700806 RCV000755051 RCV000779260 RCV000792939 RCV001202525 RCV001205475	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NEUROLOGIC ANOMALIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ETHE1-related disorder	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	CTD, ClinGen	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Brain Diseases	Brain disease	Pubtator	36891747	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases Metabolic Inborn	Brain disease	Pubtator	30391543	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	34593420	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	14732903	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	29021294		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	34593420	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31258845		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	34593420	Stimulate	★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	BEFREE	20812865		★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diarrhea	Diarrhea	Pubtator	36891747	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	16183799, 26194623		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Eosinophilic Esophagitis	Eosinophilia	Pubtator	27771676	Associate	★☆☆☆☆ Found in Text Mining only
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	BEFREE	14732903, 16183799, 17712735, 18593870, 19136963, 20657580, 20812865, 20978941, 21410200, 22020834, 22584649, 22805253, 22903887, 25198162, 25596185, 26194912, 27074420, 29526615, 30391543, 30864297		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	UNIPROT_DG	14732903, 18593870, 23144459		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	CLINVAR_DG	14732903, 16183799, 16828325, 18593870, 19136963, 25198162, 26194623, 26917598, 27391121, 29526615		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	GENOMICS_ENGLAND_DG	18593870, 27604308		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	ORPHANET_DG	18593870		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ethylmalonic encephalopathy	Ethylmalonic Encephalopathy	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gross motor development delay	Developmental delay	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Headache	Headache	Pubtator	36891747	Associate	★☆☆☆☆ Found in Text Mining only
Hypersensitivity Delayed	Hypersensitivity	Pubtator	36891747	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	38042639	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	36093993	Associate	★☆☆☆☆ Found in Text Mining only
LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY	Leigh Syndrome	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome Due To Mitochondrial Complex II Deficiency	Leigh Syndrome	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex III Deficiency	Leigh Syndrome	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex IV Deficiency	Leigh Syndrome	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex V Deficiency	Leigh Syndrome	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	12398897, 14732903		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	14732903		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	29021294		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	15132764		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	27074420, 30391543		★☆☆☆☆ Found in Text Mining only
Microvascular Angina	Microvascular angina	Pubtator	35165146	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	31477743	Associate	★☆☆☆☆ Found in Text Mining only
Necrotizing encephalopathy, infantile subacute, of Leigh	Necrotizing encephalomyelopathy	CLINGEN_DG	16376514, 18593870, 19136963, 20528888, 20978941, 25613900, 25878756, 26917598, 27830356, 28753212		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	15132764		★☆☆☆☆ Found in Text Mining only
Synovitis	Synovitis	Pubtator	29968759	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	37834012	Associate	★☆☆☆☆ Found in Text Mining only