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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ENPEP
glutamyl aminopeptidase
Chromosome 4 · 4q25
NCBI Gene: 2028Ensembl: ENSG00000138792.11HGNC: HGNC:3355UniProt: Q07075
54PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of systemic arterial blood pressure by renin-angiotensinextracellular exosomecell population proliferationmetalloaminopeptidase activityhypertensionessential hypertensionIncreased blood pressurecardiovascular disease
✦AI Summary

ENPEP encodes glutamyl aminopeptidase (also called aminopeptidase A), a membrane-bound metalloprotease that cleaves N-terminal acidic residues from peptides, particularly converting angiotensin II to angiotensin III 1. The enzyme plays a crucial role in blood pressure regulation through the renin-angiotensin system, with genetic variants associated with hypertension risk 1. ENPEP is highly expressed in kidney cortex, small intestine enterocytes, and vascular smooth muscle cells, particularly pericytes 2. The protein localizes to plasma membranes, brush borders, and lysosomal membranes, facilitating peptide catabolism and angiogenesis regulation 2. In cancer contexts, ENPEP expression is significantly altered across multiple tumor types. Iron deficiency downregulates ENPEP through SP1 transcription factor inhibition, promoting angiogenesis and metastasis in liver tumors 3. Lower ENPEP expression correlates with better response to immune checkpoint inhibitors and improved overall survival in cancer patients 4. In glioblastoma, elevated ENPEP expression associates with poor prognosis and increased immune infiltration 5. ENPEP has also emerged as a potential biomarker for early Parkinson's disease, being consistently upregulated in cerebrospinal fluid and urine of patients 6. The gene maps to chromosome 4 and shows strong correlation with ACE2 expression, suggesting possible roles in SARS-CoV-2 pathophysiology 2.

Sources cited
1
ENPEP converts angiotensin II to angiotensin III and genetic variants are associated with hypertension risk
PMID: 33421813
2
ENPEP expression patterns across tissues, cellular localization, and correlation with ACE2
PMID: 39661628
3
Iron deficiency downregulates ENPEP via SP1, promoting angiogenesis and metastasis in liver tumors
PMID: 37085059
4
Lower ENPEP expression correlates with better immune checkpoint inhibitor response and survival
PMID: 34862755
5
Elevated ENPEP in glioblastoma associates with poor prognosis and immune infiltration
PMID: 35464443
6
ENPEP is upregulated in CSF and urine of early Parkinson's disease patients
PMID: 38467937
7
ENPEP gene location on chromosome 4q25
PMID: 9268642
Disease Associationsⓘ20
hypertensionOpen Targets
0.67Moderate
essential hypertensionOpen Targets
0.59Moderate
Increased blood pressureOpen Targets
0.50Moderate
cardiovascular diseaseOpen Targets
0.48Moderate
response to xenobiotic stimulusOpen Targets
0.35Weak
atrial fibrillationOpen Targets
0.34Weak
hypertensive heart diseaseOpen Targets
0.33Weak
tooth diseaseOpen Targets
0.30Weak
ocular hypotensionOpen Targets
0.27Weak
lacrimal apparatus diseaseOpen Targets
0.26Weak
parasitic infectionOpen Targets
0.26Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.25Weak
neurodegenerative diseaseOpen Targets
0.24Weak
deficiency anemiaOpen Targets
0.20Weak
autismOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.10Suggestive
myelodysplastic syndromeOpen Targets
0.10Suggestive
cervical carcinomaOpen Targets
0.08Suggestive
heart failureOpen Targets
0.08Suggestive
myocardial infarctionOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
FIRIBASTATPhase III
Aminopeptidase A inhibitor
hypertension
TOSEDOSTATPhase II
Aminopeptidase inhibitor
acute myeloid leukemia by FAB classification
Related Genes
ITIH4Protein interaction100%CXCR4Protein interaction100%CD4Protein interaction99%CCR5Protein interaction99%DPP4Protein interaction99%AGTProtein interaction93%
Tissue Expression6 tissues
Liver
100%
Heart
34%
Lung
24%
Brain
12%
Ovary
7%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
ENPEPITIH4CXCR4CD4CCR5DPP4AGT
PROTEIN STRUCTURE
Preparing viewer…
PDB4KX7 · 2.15 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.72–1.03]
RankingsWhere ENPEP stands among ~20K protein-coding genes
  • #8,310of 20,598
    Most Researched54
  • #10,119of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedENPEP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.
PMID: 30824564
Mol Syst Biol · 2019
1.00
2
Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease.
PMID: 38467937
Acta Neuropathol · 2024
0.90
3
Aminopeptidase A (ENPEP) gene polymorphisms and preeclampsia: Descriptive analysis.
PMID: 33421813
Eur J Obstet Gynecol Reprod Biol · 2021
0.80
4
High-resolution genetic map of the human glutamyl aminopeptidase gene (ENPEP).
PMID: 9268642
Genomics · 1997
0.70
5
Iron deficiency downregulates ENPEP to promote angiogenesis in liver tumors.
PMID: 37085059
J Nutr Biochem · 2023
0.60