ENPEP
protein-codingglutamyl aminopeptidase, the group of CD molecules|Aminopeptidases|M1 metallopeptidases
Gene summary
The ENPEP gene encodes glutamyl aminopeptidase, a type II integral membrane protein with an extracellular zinc-binding domain. This protein can upregulate blood pressure by cleaving the N-terminal aspartate from angiotensin II, and can regulate blood vessel formation and enhance tumorigenesis in some tissues. Along with ANPEP and DPP4, ENPEP was found to be a candidate co-receptor for the coronavirus SARS-CoV-2, which causes COVID-19. [provided by RefSeq, Apr 2020]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~199.6 kbGenCC 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 ENPEP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001977.4. 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 | 1 | 2 | 3 | |||
| missense | 134 | 2 | 3 | 139 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 138 | 2 | 5 | 145 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001968.3 | 20 | MANE Select | |
| Ensembl | ENSP00000265162.5 | 20 | MANE Select | |
| RefSeq | NP_001366540.1 | 20 | Standard | |
| RefSeq | NP_001366541.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Renin-angiotensin system - Homo sapiens (human)
- Peptide hormone metabolism
- Metabolism of proteins
- Metabolism of Angiotensinogen to Angiotensins
Biological Process
- angiogenesis
- angiotensin maturation
- regulation of systemic arterial blood pressure by renin-angiotensin
- proteolysis
- cell-cell signaling
Molecular Function
- aminopeptidase activity
- metallopeptidase activity
- zinc ion binding
- peptide binding
- metalloaminopeptidase activity
Cellular Component
- cytoplasm
- lysosomal membrane
- plasma membrane
- integral component of plasma membrane
- brush border
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265162
- Coding exons
- 20
- Length
- 199553
- Individuals with no LoFs
- 123648
- Homozygous LoFs
- 14
- Heterozygous LoFs
- 2086
- Defined
- 125748
- p
- 0.00839
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.116 | 526 | 519 | 1.01 | 0.0000284 | 6276 |
| Missense (PolyPhen) | 202 | 194.37 | 1.0393 | 2368 | ||
| Synonymous | -0.383 | 207 | 200 | 1.03 | 0.0000126 | 1785 |
| Loss of Function | 0.707 | 46 | 51.5 | 0.894 | 0.00000247 | 623 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0025 | 0.0023 | notable |
| Latino/Admixed American | 0.0037 | 0.0036 | notable |
| Ashkenazi Jewish | 0.0047 | 0.0047 | notable |
| East Asian | 0.00082 | 0.00082 | rare |
| Finnish | 0.0083 | 0.0082 | notable |
| European (Non-Finnish) | 0.014 | 0.014 | notable |
| South Asian | 0.0035 | 0.0034 | notable |
| Other | 0.0087 | 0.0083 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates central hypertension through its calcium- modulated preference to cleave N-terminal acidic residues from peptides such as angiotensin II. {ECO:0000305|PubMed:23888046}.;
Recessive Scores
- pRec
- 0.479
Intolerance Scores
- LoFtool
- 0.979
- RVIS EVS
- 0.39
- RVIS percentile EVS
- 75.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.286
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |