ECE1

protein-coding

endothelin converting enzyme 1, the group of M13 metallopeptidases

Gene summary

The protein encoded by this gene is involved in proteolytic processing of endothelin precursors to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Sep 2009]

Previous symbols:

MANE transcript

NM_001397.3

Inheritance

ClinVar variants

P:3U:115B:36

Top phenotype

Hirschsprung disease, cardiac defects, and autonomic dysfunction

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr1:21,217,247-21,345,572

External References & Databases

Ensembl (ENSG00000117298)

Transcript & Mutation Effects

hg38 • Region Span ~128.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

essential hypertension, geneticNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007781

Submitter: Labcorp Genetics (formerly Invitae)

Hirschsprung disease, cardiac defects, and autonomic dysfunctionLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013473

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hirschsprung disease, cardiac defects, and autonomic dysfunctionAD

Manifestation: Cardiovascular; Genitourinary; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 9915973

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ECE1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 25

ECE1-related disorderTotal: 17

Hirschsprung disease, cardiac defects, and autonomic dysfunctionTotal: 7

Essential hypertension, geneticTotal: 3

Aganglionic megacolonTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001397.3. 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	24 clinvar	3 clinvar	29
missense		3 clinvar	104 clinvar	7 clinvar	2 clinvar	116
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	3	115	31	5	154

Highest pathogenic variant AF is 0.00009541299

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001397.3	RefSeq	NP_001388.1	19	MANE Select
ENST00000374893.11	Ensembl	ENSP00000364028.6	19	MANE Select
NM_001113347.2	RefSeq	NP_001106818.1	17	Standard
NM_001113348.2	RefSeq	NP_001106819.1	19	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ece1	Danio rerio	Structure: ceratobranchial cartilage Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

ece1

Danio rerio

Structure: ceratobranchial cartilage

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endothelin Pathways
Corticotropin-releasing hormone signaling pathway
Melatonin metabolism and effects
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Signaling by GPCR

Biological Process

positive regulation of receptor recycling
regulation of systemic arterial blood pressure by endothelin
heart development
substance P catabolic process
bradykinin catabolic process

Molecular Function

endopeptidase activity
metalloendopeptidase activity
protein binding
zinc ion binding
peptide hormone binding

Cellular Component

lysosomal membrane
endosome
plasma membrane
external side of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374893
Coding exons: 19
Length: 128258
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.31	315	453	0.695	0.0000294	5060
Missense (PolyPhen)		96	196.1	0.48956		2250
Synonymous	0.0901	186	188	0.992	0.0000137	1445
Loss of Function	4.91	7	40.9	0.171	0.00000198	480

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000070	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Converts big endothelin-1 to endothelin-1. {ECO:0000269|PubMed:9396733}.;

Recessive Scores

pRec: 0.390

Intolerance Scores

LoFtool: 0.0216
RVIS EVS: -0.69
RVIS percentile EVS: 15.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.531

Gene Damage Prediction

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