ECE2
protein-codingendothelin converting enzyme 2, the group of M13 metallopeptidases
Gene summary
Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0004975
Submitter: Illumina
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ECE2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001100121.2. 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 | 2 | 4 | |||
| missense | 65 | 4 | 1 | 70 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 66 | 6 | 3 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001093591.1 | 19 | MANE Select | |
| Ensembl | ENSP00000385846.3 | 19 | MANE Select | |
| RefSeq | NP_001032401.1 | 18 | Standard | |
| RefSeq | NP_001093590.1 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ece2b | Danio rerio | Structure: iridophore Quality: ridged abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by GPCR
- Signal Transduction
- Peptide ligand-binding receptors
- Class A/1 (Rhodopsin-like receptors)
- GPCR ligand binding
Biological Process
- peptide hormone processing
- methylation
Molecular Function
- metalloendopeptidase activity
- methyltransferase activity
- metal ion binding
Cellular Component
- Golgi membrane
- integral component of membrane
- transport vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000402825
- Coding exons
- 19
- Length
- 43382
- Individuals with no LoFs
- 125556
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 192
- Defined
- 125748
- p
- 0.000764
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.190 | 521 | 533 | 0.977 | 0.0000314 | 5764 |
| Missense (PolyPhen) | 258 | 272 | 0.94853 | 3014 | ||
| Synonymous | -0.404 | 226 | 218 | 1.03 | 0.0000126 | 1738 |
| Loss of Function | 1.50 | 39 | 50.5 | 0.772 | 0.00000260 | 519 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0.00090 | 0.00089 | rare |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00091 | 0.00089 | rare |
| South Asian | 0.00051 | 0.00049 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Converts big endothelin-1 to endothelin-1. Also involved in the processing of various neuroendocrine peptides, including neurotensin, angiotensin I, substance P, proenkephalin-derived peptides, and prodynorphin-derived peptides. May play a role in amyloid-beta processing (By similarity). {ECO:0000250|UniProtKB:B2RQR8, ECO:0000269|PubMed:12560336}.;
Recessive Scores
- pRec
- 0.0979
Intolerance Scores
- LoFtool
- 0.0767
- RVIS EVS
- -0.87
- RVIS percentile EVS
- 10.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.263
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |