ANPEP Gene (CD13): Aminopeptidase N Function, Disease Associations, and Expression
Comprehensive biomedical overview of the ANPEP gene, encoding aminopeptidase N (CD13), including genomic data, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | ANPEP |
|---|---|
| Full Name | Alanyl Aminopeptidase, Membrane |
| Gene Type | Protein coding |
| Chromosomal Location | 15q25.3 |
| NCBI Gene ID | 290 ncbi.nlm.nih.gov/gene/290 |
| Ensembl ID | ENSG00000166825 |
| UniProt ID | P15144 |
| OMIM ID | 151530 |
| HGNC ID | 500 |
| Aliases | CD13, APN, GP150, LAP1, PEPN |
Description
The ANPEP gene encodes aminopeptidase N (APN), also known as CD13, a type II integral membrane zinc-dependent metalloprotease. It is widely expressed on the surface of various cells, including epithelial cells of the small intestine and kidney proximal tubules, myeloid cells, and endothelial cells. APN functions to cleave neutral amino acids from the N-terminus of peptides and proteins, playing critical roles in protein digestion, peptide hormone regulation, angiogenesis, cell migration, and antigen processing. It also serves as a receptor for certain viruses, including human coronaviruses (e.g., HCoV-229E) and cytomegalovirus. Dysregulation of ANPEP expression is implicated in various cancers, inflammatory conditions, and cardiovascular diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of ANPEP/CD13 promotes tumor cell invasion, angiogenesis, and metastasis through its proteolytic activity on extracellular matrix components and regulation of signaling pathways (e.g., PI3K/Akt). | High expression correlates with poor prognosis in various solid tumors (e.g., gastric, colon, pancreatic cancer) as documented in numerous studies indexed in PubMed/NCBI. |
| Viral Infection (HCoV-229E) | ANPEP serves as the primary cellular receptor for Human Coronavirus 229E (HCoV-229E). The virus binds to the extracellular domain of CD13 to enter host cells. | Identified as a receptor in multiple studies; interaction confirmed via co-immunoprecipitation and viral entry assays (NCBI, UniProt). |
| Inflammatory Bowel Disease (IBD) | Altered ANPEP expression and activity contribute to intestinal inflammation by modulating peptide metabolism and immune cell function. | Expression changes observed in intestinal biopsies from IBD patients; functional studies in animal models (OMIM, PubMed). |
| Hypertension | ANPEP is involved in the metabolism of vasoactive peptides, such as angiotensin II and bradykinin, potentially influencing blood pressure regulation. | Genetic association studies have linked ANPEP variants to hypertension risk in some populations (OMIM, PubMed). |
| Leukemia | CD13 is a well-established myeloid differentiation marker. Its expression is used for diagnosis and classification of acute myeloid leukemia (AML). | Flow cytometry detection of CD13 is a standard diagnostic criterion for AML (NCBI, PubMed). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 104.2 | High |
| Kidney | 82.5 | High |
| Liver | 31.8 | Medium |
| Lung | 20.1 | Medium |
| Spleen | 15.4 | Medium |
| Bone Marrow | 12.3 | Medium |
| Brain | 5.2 | Low |
| Heart | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (Promyeloblast) | 45.3 | High expression; used as a model for myeloid differentiation. |
| K-562 (Chronic Myelogenous Leukemia) | 38.7 | High expression; CD13 is a marker for myeloid lineage. |
| A549 (Lung Carcinoma) | 22.5 | Moderate expression; relevant for lung cancer studies. |
| HepG2 (Hepatocellular Carcinoma) | 18.9 | Moderate expression; liver cancer model. |
| MCF7 (Breast Adenocarcinoma) | 8.4 | Low expression; breast cancer cell line. |
| SH-SY5Y (Neuroblastoma) | 2.1 | Low expression; neuronal model. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2564978 (Intronic variant) | SNV | Minor allele frequency ~0.3 (1000 Genomes) | Associated with altered ANPEP expression levels in some studies; potential link to hypertension susceptibility. |
| rs6496604 (Intronic variant) | SNV | Minor allele frequency ~0.4 (1000 Genomes) | Reported in genome-wide association studies for blood pressure traits. |
| c.1540G>A (p.Ala514Thr) | Missense | Rare (<0.01) | Located in the extracellular domain; may affect enzyme activity or substrate specificity, but clinical significance is not fully established. |
| c.1966C>T (p.Arg656Cys) | Missense | Rare (<0.01) | Potential impact on protein folding or stability; observed in cancer samples (COSMIC). |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in ANPEP are rare and not well-documented in germline databases. Somatic mutations or downregulation in tumors can lead to reduced enzymatic activity, potentially affecting peptide processing and immune modulation.
Gain of Function (GOF)
Gain-of-function is primarily observed at the expression level (overexpression) rather than through specific activating mutations. Increased ANPEP expression enhances tumor invasiveness and angiogenesis.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for ANPEP. The protein functions as a homodimer, but no evidence suggests that mutant monomers can inhibit the wild-type protein's function.
View complete mutation data：
Gene Ontology (GO)
| • Aminopeptidase activity | • Metallopeptidase activity |
| • Zinc ion binding | • Proteolysis |
| • Cell adhesion | • Angiogenesis |
| • Viral entry into host cell | • Peptide metabolic process |
| • Extracellular matrix organization | • Signal transduction |
Pathways
• Angiotensin-converting enzyme 2 (ACE2) pathway (related to peptide metabolism)
• Bradykinin degradation pathway
• Extracellular matrix degradation
• Tumor angiogenesis
• Antigen processing and presentation
Protein Summary
Aminopeptidase N (APN/CD13) is a 150 kDa type II transmembrane glycoprotein that forms a homodimer on the cell surface. It is a zinc-dependent metalloprotease that removes N-terminal neutral amino acids from peptides. The protein has a short N-terminal cytoplasmic domain, a single transmembrane helix, and a large extracellular C-terminal domain containing the catalytic site. APN is involved in the final stages of protein digestion, regulation of bioactive peptide signaling (e.g., enkephalins, angiotensins), and processing of cytokines and chemokines. It also plays a role in cell-cell adhesion and migration. As CD13, it is a key myeloid differentiation marker and a receptor for certain coronaviruses. Its expression is upregulated in many cancers, where it promotes tumor progression and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ANPEP Knockout HEK293 Cell Line | EDJ-KQ1953 | Human | 290 | Details Get a Quote |
| ANPEP Knockout A-549 Cell Line | EDJ-KQ21904 | Human | 290 | Details Get a Quote |
| ANPEP Knockout HeLa Cell Line | EDJ-KQ21905 | Human | 290 | Details Get a Quote |
| ANPEP Knockout IPEC-J2 Cell Line | EDJ-KZ542 | Pig | 397520 | Details Get a Quote |
| ANPEP Knockout HCT 116 Cell Line | EDJ-KQ69583 | Human | 290 | Details Get a Quote |
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