ECE1

Chr 1ADMulti

endothelin converting enzyme 1

Also known as: ECE

NCBI Gene: 1889ENSG00000117298UniProt: P42892

The protein converts big endothelin-1 to endothelin-1, a vasoactive peptide important for vascular tone and development. Mutations cause Hirschsprung disease with cardiac defects and autonomic dysfunction, with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variation (pLI 0.96), reflecting its critical role in cardiovascular and enteric nervous system development.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Hirschsprung disease, cardiac defects, and autonomic dysfunctionMIM #613870
AD
{Hypertension, essential, susceptibility to}MIM #145500
Multi
0
Active trials
25
Pubs (1 yr)
13
P/LP submissions
31%
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— ECE1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 104 VUS of 186 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.960
Z-score 4.91
OE 0.17 (0.10–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.31Z-score
OE missense 0.70 (0.63–0.76)
315 obs / 453.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.10–0.32)
0≤0.351.4
Missense OE0.70 (0.63–0.76)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 7 / 40.9Missense obs/exp: 315 / 453.2Syn Z: 0.09
DN
0.4189th %ile
GOF
0.5759th %ile
LOF
0.4726th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · LOEUF 0.32

Literature Evidence

LOFA loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunctionPMID:9915973

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic4
VUS104
Likely Benign27
Benign14
Conflicting1
9
Pathogenic
4
Likely Pathogenic
104
VUS
27
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
8
0
9
Likely Pathogenic
0
3
1
0
4
VUS
1
96
7
0
104
Likely Benign
0
6
5
16
27
Benign
0
3
6
5
14
Conflicting
—1
Total11092721159

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ECE1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exploring the evolutionary conservation and functional implications of Endothelin Converting Enzyme 1 (ECE1) in lamprey (Lethenteron reissneri).
Zhang S et al.·Fish Physiol Biochem
2025Functional
DNA damage repair factor Rad18 controls virulence partially via transcriptional suppression of genes HWP1 and ECE1 in Candida albicans.
Chen R et al.·Virulence
2024Open Access
Candida Albicans Candidalysin ECE1 Gene - A Potent Virulence Factor for Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.
Subramani MB et al.·Indian J Dent Res
2024
The Analysis of ECE1 and PPARG Variants in the Development of Osteopenia and Osteoporosis in Postmenopausal Women.
Uzar I et al.·Biomedicines
2024Open Access
A non-canonical role of endothelin converting enzyme 1 (ECE1) in promoting lung cancer development via directly targeting protein kinase B (AKT).
Chen L et al.·J Gene Med
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients