ETHE1

ETHE1 persulfide dioxygenase, the group of MBL domain containing glyoxalase 2 subfamily

Basic information

Region (hg38): 19:43506719-43527230

Links

ENSG00000105755NCBI:23474OMIM:608451HGNC:23287Uniprot:O95571AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • ethylmalonic encephalopathy (Definitive), mode of inheritance: AR
  • ethylmalonic encephalopathy (Strong), mode of inheritance: AR
  • ethylmalonic encephalopathy (Supportive), mode of inheritance: AR
  • Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ethylmalonic encephalopathyARBiochemicalThe condition can manifest with features including neurological impairment and chronic diarrhea, and dietary (eg, with restriction of branched amino acids, fatty acids, and methionine) and medical treatment (eg, with metronidazole and N-acetylcysteine) has been reported as having clinical benefitBiochemical; Cardiovascular; Gastrointestinal; Neurologic14732903; 18593870; 20528888; 20657580; 20978941; 21472225; 22584649; 22805253

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ETHE1 gene.

  • Ethylmalonic encephalopathy (34 variants)
  • not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ETHE1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
3
clinvar
124
clinvar
2
clinvar
129
missense
4
clinvar
9
clinvar
55
clinvar
4
clinvar
1
clinvar
73
nonsense
6
clinvar
4
clinvar
1
clinvar
11
start loss
3
clinvar
3
frameshift
20
clinvar
10
clinvar
30
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
2
clinvar
15
clinvar
17
splice region
1
4
27
1
33
non coding
3
clinvar
58
clinvar
18
clinvar
79
Total 35 38 63 186 21

Highest pathogenic variant AF is 0.0000263

Variants in ETHE1

This is a list of pathogenic ClinVar variants found in the ETHE1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
19-43506758-T-G Ethylmalonic encephalopathy Uncertain significance (Jan 12, 2018)894208
19-43506795-C-A Ethylmalonic encephalopathy Benign (Aug 18, 2020)329439
19-43506802-C-T Ethylmalonic encephalopathy Uncertain significance (Jan 13, 2018)894209
19-43506819-T-C Ethylmalonic encephalopathy Uncertain significance (Jan 13, 2018)329440
19-43506853-G-A Ethylmalonic encephalopathy Likely benign (Jun 11, 2022)2194552
19-43506853-G-T Ethylmalonic encephalopathy Likely benign (Sep 10, 2023)1615457
19-43506854-G-A Ethylmalonic encephalopathy Uncertain significance (Aug 18, 2020)658833
19-43506855-C-T not specified Uncertain significance (Oct 17, 2023)2637783
19-43506856-A-C Ethylmalonic encephalopathy Likely benign (Jan 24, 2024)1606159
19-43506856-A-G Ethylmalonic encephalopathy Likely benign (Oct 22, 2021)1611761
19-43506858-T-C Ethylmalonic encephalopathy Uncertain significance (Feb 03, 2022)959249
19-43506859-G-A Ethylmalonic encephalopathy Likely benign (Aug 29, 2023)2755780
19-43506868-C-T Ethylmalonic encephalopathy Likely benign (Aug 06, 2022)752698
19-43506873-C-T Likely pathogenic (Jul 01, 2020)623957
19-43506874-A-G Ethylmalonic encephalopathy Likely benign (Mar 10, 2023)2009639
19-43506878-C-T Inborn genetic diseases Uncertain significance (May 24, 2023)2525174
19-43506881-A-C Ethylmalonic encephalopathy Uncertain significance (Dec 28, 2023)1442283
19-43506883-G-A Ethylmalonic encephalopathy Likely benign (Feb 04, 2022)2093181
19-43506890-G-A Ethylmalonic encephalopathy Uncertain significance (Aug 21, 2022)894210
19-43506897-CA-C Ethylmalonic encephalopathy Likely pathogenic (-)1801827
19-43506909-G-A Ethylmalonic encephalopathy Likely benign (Jan 05, 2024)2169275
19-43506910-G-C Ethylmalonic encephalopathy Likely benign (Feb 21, 2023)2884877
19-43507745-C-T Benign (Aug 06, 2019)1260599
19-43507763-T-C Ethylmalonic encephalopathy Benign (May 07, 2021)671647
19-43507763-TAGACCCAGGAGTCCAGGCCCCCAGCCTCTCCTCCCTC-T Benign (Jun 26, 2018)1248611

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ETHE1protein_codingprotein_codingENST00000292147 720526
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.000004600.4151257270201257470.0000795
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9571101420.7740.000007621621
Missense in Polyphen2952.9690.54749595
Synonymous0.4475660.40.9270.00000309536
Loss of Function0.490910.70.8394.72e-7126

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001790.000179
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.0001070.000105
Middle Eastern0.00005440.0000544
South Asian0.00003270.0000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
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). {ECO:0000269|PubMed:12398897, ECO:0000269|PubMed:14732903, ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}.;
Pathway
Sulfur metabolism - Homo sapiens (human);Sulfide oxidation to sulfate;Degradation of cysteine and homocysteine;Metabolism of amino acids and derivatives;Metabolism;Sulfur amino acid metabolism (Consensus)

Recessive Scores

pRec
0.166

Intolerance Scores

loftool
0.329
rvis_EVS
-0.32
rvis_percentile_EVS
31.46

Haploinsufficiency Scores

pHI
0.0879
hipred
Y
hipred_score
0.600
ghis
0.458

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.752

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ethe1
Phenotype
homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process
glutathione metabolic process;sulfide oxidation, using sulfide:quinone oxidoreductase;hydrogen sulfide metabolic process
Cellular component
nucleoplasm;cytoplasm;mitochondrion;mitochondrial matrix
Molecular function
iron ion binding;hydrolase activity, acting on ester bonds;sulfur dioxygenase activity