ECH1

protein-coding

enoyl-CoA hydratase 1

Gene summary

This gene encodes a member of the hydratase/isomerase superfamily. The gene product shows high sequence similarity to enoyl-coenzyme A (CoA) hydratases of several species, particularly within a conserved domain characteristic of these proteins. The encoded protein, which contains a C-terminal peroxisomal targeting sequence, localizes to the peroxisome. The rat ortholog, which localizes to the matrix of both the peroxisome and mitochondria, can isomerize 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA, indicating that it is a delta3,5-delta2,4-dienoyl-CoA isomerase. This enzyme functions in the auxiliary step of the fatty acid beta-oxidation pathway. Expression of the rat gene is induced by peroxisome proliferators. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001398.3

Inheritance

—

ClinVar variants

U:60B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr19:38,815,422-38,831,841

External References & Databases

Ensembl (ENSG00000104823)

Transcript & Mutation Effects

hg38 • Region Span ~16.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ECH1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001398.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			54 clinvar		1 clinvar	55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	60	0	1	61

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001398.3	RefSeq	NP_001389.2	10	MANE Select
ENST00000221418.9	Ensembl	ENSP00000221418.3	10	MANE Select
ENST00000594164.5	Ensembl	ENSP00000470839.1	2	Standard
ENST00000595470.1	Ensembl	ENSP00000470809.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peroxisome - Homo sapiens (human)
Valproic Acid Pathway, Pharmacokinetics
Fatty Acid Biosynthesis
Liver steatosis AOP
Metabolism of proteins

Biological Process

protein targeting to peroxisome
fatty acid beta-oxidation

Molecular Function

signaling receptor binding
protein binding
delta3,5-delta2,4-dienoyl-CoA isomerase activity

Cellular Component

mitochondrion
peroxisome
peroxisomal matrix
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221418
Coding exons: 10
Length: 16584
Individuals with no LoFs: 125639
Homozygous LoFs: 1
Heterozygous LoFs: 108
Defined: 125748
p: 0.000434

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0436	205	207	0.991	0.0000120	2115
Missense (PolyPhen)		75	84.48	0.88779		861
Synonymous	0.786	82	91.6	0.895	0.00000626	664
Loss of Function	1.16	12	17.2	0.698	8.06e-7	184

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00078	0.00078	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00076	0.00076	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00039	0.00039	rare
South Asian	0.00043	0.00042	rare
Other	0.00098	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isomerization of 3-trans,5-cis-dienoyl-CoA to 2-trans,4- trans-dienoyl-CoA. {ECO:0000250}.;

Recessive Scores

pRec: 0.203

Intolerance Scores

LoFtool: 0.745
RVIS EVS: 0.2
RVIS percentile EVS: 67.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.884

Gene Damage Prediction

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