ECHS1

enoyl-CoA hydratase, short chain 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 10:133362485-133373354

Links

ENSG00000127884 ∙ NCBI:1892 ∙ OMIM:602292 ∙ HGNC:3151 ∙ Uniprot:P30084 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (Strong), mode of inheritance: AR
• mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (Strong), mode of inheritance: AR
• mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (Strong), mode of inheritance: AR
• mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (Moderate), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR
• mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	25125611; 25393721; 26251176; 29575569

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ECHS1 gene.

• not provided (10 variants)
• Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (8 variants)
• Leigh syndrome (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ECHS1 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			1	62	3	66
missense	6	25	81	2	2	116
nonsense	1					1
start loss	3	2				5
frameshift	3	2	1			6
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region		1	6	14	1	22
non coding			3	49	33	85
Total	14	31	87	113	38

Highest pathogenic variant AF is 0.0000395

Variants in ECHS1

This is a list of pathogenic ClinVar variants found in the ECHS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-133362587-G-A			Benign (Jun 14, 2018)
10-133362754-G-A			Benign (Jun 26, 2018)
10-133362871-C-G			Uncertain significance (Jul 19, 2022)
10-133362874-G-C			Uncertain significance (Dec 06, 2022)
10-133362876-C-T		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
10-133362882-A-G			Uncertain significance (Oct 15, 2020)
10-133362883-G-GTT		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Pathogenic (Oct 25, 2017)
10-133362886-G-A			Likely benign (Sep 26, 2023)
10-133362888-CCTTT-C			Uncertain significance (Oct 03, 2022)
10-133362889-C-T			Likely benign (Jul 13, 2022)
10-133362890-T-C			Uncertain significance (Aug 27, 2021)
10-133362894-T-C		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Likely pathogenic (Jan 25, 2018)
10-133362895-C-G			Uncertain significance (Jan 05, 2022)
10-133362895-C-T			Likely benign (Nov 03, 2023)
10-133362905-A-G		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Conflicting classifications of pathogenicity (Oct 13, 2022)
10-133362907-C-T		ECHS1-related disorder	Likely benign (Jan 12, 2024)
10-133362908-G-A		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Uncertain significance (Jun 28, 2018)
10-133362909-C-T		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Likely pathogenic (Dec 11, 2023)
10-133362910-G-T			Likely benign (Oct 03, 2023)
10-133362911-G-A		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Pathogenic/Likely pathogenic (Apr 12, 2024)
10-133362916-C-T		not specified	Likely benign (Nov 07, 2023)
10-133362919-T-C			Likely benign (Oct 28, 2022)
10-133362924-T-C		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency • Inborn genetic diseases	Pathogenic/Likely pathogenic (Dec 02, 2023)
10-133362926-C-T			Uncertain significance (Oct 25, 2023)
10-133362927-G-A		Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency	Uncertain significance (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ECHS1	protein_coding	protein_coding	ENST00000368547	8	11210

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000877	0.943	125682	0	59	125741	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.863	131	162	0.809	0.00000908	1867
Missense in Polyphen		41	74.02	0.55391		823
Synonymous	-0.419	70	65.7	1.07	0.00000429	536
Loss of Function	1.69	7	13.8	0.509	6.78e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000729	0.000727
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000232	0.000229
Middle Eastern	0.000163	0.000163
South Asian	0.000296	0.000294
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Straight-chain enoyl-CoA thioesters from C4 up to at least C16 are processed, although with decreasing catalytic rate. Has high substrate specificity for crotonyl-CoA and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA and methacrylyl-CoA. It is noteworthy that binds tiglyl-CoA, but hydrates only a small amount of this substrate. {ECO:0000269|PubMed:26251176}.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Butanoate metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Fatty acid elongation - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Long chain acyl-CoA dehydrogenase deficiency (LCAD);Lysine Degradation;3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Hyperlysinemia I, Familial;Malonyl-coa decarboxylase deficiency;2-aminoadipic 2-oxoadipic aciduria;Trifunctional protein deficiency;Long-chain-3-hydroxyacyl-coa dehydrogenase deficiency (LCHAD);Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Malonic Aciduria;Fatty Acid Elongation In Mitochondria;Pyridoxine dependency with seizures;Saccharopinuria/Hyperlysinemia II;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Maple Syrup Urine Disease;Propanoate Metabolism;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Glutaric Aciduria Type I;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids;Mitochondrial Beta-Oxidation of Medium Chain Saturated Fatty Acids;Mitochondrial Beta-Oxidation of Long Chain Saturated Fatty Acids;Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD);Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Hyperlysinemia II or Saccharopinuria;Butyrate Metabolism;Beta-Ketothiolase Deficiency;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Fatty Acid Biosynthesis;Liver steatosis AOP;Tryptophan metabolism;Butanoate metabolism;Metabolism of lipids;Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA;Beta oxidation of octanoyl-CoA to hexanoyl-CoA;Beta oxidation of hexanoyl-CoA to butanoyl-CoA;Beta oxidation of butanoyl-CoA to acetyl-CoA;mitochondrial fatty acid beta-oxidation of saturated fatty acids;Mitochondrial Fatty Acid Beta-Oxidation;3-oxo-10R-octadecatrienoate beta-oxidation;Leukotriene metabolism;Saturated fatty acids beta-oxidation;Trihydroxycoprostanoyl-CoA beta-oxidation;Metabolism;Lysine degradation;Fatty acid metabolism;Propanoate metabolism;valine degradation;Mono-unsaturated fatty acid beta-oxidation;Omega-6 fatty acid metabolism;Valine, leucine and isoleucine degradation;Butanoate metabolism;Propanoate metabolism;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Di-unsaturated fatty acid beta-oxidation;Vitamin E metabolism;isoleucine degradation;fatty acid β-oxidation (peroxisome);fatty acid β-oxidation;glutaryl-CoA degradation;Tryptophan degradation;Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA;Valine Leucine Isoleucine degradation (Consensus)

Intolerance Scores

• loftool: 0.498
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.35

Haploinsufficiency Scores

• pHI: 0.0927
• hipred: Y
• hipred_score: 0.580
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Echs1

Gene ontology

• Biological process: fatty acid beta-oxidation
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: enoyl-CoA hydratase activity;protein binding