ETHE1
Basic information
Region (hg38): 19:43506719-43527230
Links
Phenotypes
GenCC
Source:
- 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:
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
- 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 | 124 | 129 | ||||
missense | 55 | 73 | ||||
nonsense | 11 | |||||
start loss | 3 | |||||
frameshift | 20 | 10 | 30 | |||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 15 | 17 | ||||
splice region | 1 | 4 | 27 | 1 | 33 | |
non coding | 58 | 18 | 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) | ||
19-43506795-C-A | Ethylmalonic encephalopathy | Benign (Aug 18, 2020) | ||
19-43506802-C-T | Ethylmalonic encephalopathy | Uncertain significance (Jan 13, 2018) | ||
19-43506819-T-C | Ethylmalonic encephalopathy | Uncertain significance (Jan 13, 2018) | ||
19-43506853-G-A | Ethylmalonic encephalopathy | Likely benign (Jun 11, 2022) | ||
19-43506853-G-T | Ethylmalonic encephalopathy | Likely benign (Sep 10, 2023) | ||
19-43506854-G-A | Ethylmalonic encephalopathy | Uncertain significance (Aug 18, 2020) | ||
19-43506855-C-T | not specified | Uncertain significance (Oct 17, 2023) | ||
19-43506856-A-C | Ethylmalonic encephalopathy | Likely benign (Jan 24, 2024) | ||
19-43506856-A-G | Ethylmalonic encephalopathy | Likely benign (Oct 22, 2021) | ||
19-43506858-T-C | Ethylmalonic encephalopathy | Uncertain significance (Feb 03, 2022) | ||
19-43506859-G-A | Ethylmalonic encephalopathy | Likely benign (Aug 29, 2023) | ||
19-43506868-C-T | Ethylmalonic encephalopathy | Likely benign (Aug 06, 2022) | ||
19-43506873-C-T | Likely pathogenic (Jul 01, 2020) | |||
19-43506874-A-G | Ethylmalonic encephalopathy | Likely benign (Mar 10, 2023) | ||
19-43506878-C-T | Inborn genetic diseases | Uncertain significance (May 24, 2023) | ||
19-43506881-A-C | Ethylmalonic encephalopathy | Uncertain significance (Dec 28, 2023) | ||
19-43506883-G-A | Ethylmalonic encephalopathy | Likely benign (Feb 04, 2022) | ||
19-43506890-G-A | Ethylmalonic encephalopathy | Uncertain significance (Aug 21, 2022) | ||
19-43506897-CA-C | Ethylmalonic encephalopathy | Likely pathogenic (-) | ||
19-43506909-G-A | Ethylmalonic encephalopathy | Likely benign (Jan 05, 2024) | ||
19-43506910-G-C | Ethylmalonic encephalopathy | Likely benign (Feb 21, 2023) | ||
19-43507745-C-T | Benign (Aug 06, 2019) | |||
19-43507763-T-C | Ethylmalonic encephalopathy | Benign (May 07, 2021) | ||
19-43507763-TAGACCCAGGAGTCCAGGCCCCCAGCCTCTCCTCCCTC-T | Benign (Jun 26, 2018) |
GnomAD
Source:
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:
- 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