ETHE1

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

Basic information

Region (hg38): 19:43506719-43527230

Links

ENSG00000105755

∙ NCBI:23474 ∙ OMIM:608451 ∙ HGNC:23287 ∙ Uniprot:O95571 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ethylmalonic encephalopathy	AR	Biochemical	The 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 benefit	Biochemical; Cardiovascular; Gastrointestinal; Neurologic	14732903; 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 (385 variants)
not_provided (43 variants)
Inborn_genetic_diseases (23 variants)
not_specified (14 variants)
ETHE1-related_disorder (6 variants)
Abnormality_of_the_nervous_system (1 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. These statistics are base on transcript: NM_000014297.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	133 clinvar	2 clinvar	140
missense	4 clinvar	13 clinvar	81 clinvar	3 clinvar	1 clinvar	102
nonsense	6 clinvar	4 clinvar	1 clinvar			11
start loss	3	1				4
frameshift	22 clinvar	15 clinvar	2 clinvar			39
splice donor/acceptor (+/-2bp)	4 clinvar	16 clinvar				20
Total	39	49	89	136	3

Highest pathogenic variant AF is 0.000024782319

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ETHE1	protein_coding	protein_coding	ENST00000292147	7	20526

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000460	0.415	125727	0	20	125747	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.957	110	142	0.774	0.00000762	1621
Missense in Polyphen		29	52.969	0.54749		595
Synonymous	0.447	56	60.4	0.927	0.00000309	536
Loss of Function	0.490	9	10.7	0.839	4.72e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000179	0.000179
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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