ERAP2 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the ERAP2 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | ERAP2 |
|---|---|
| Full Name | Endoplasmic Reticulum Aminopeptidase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q15 |
| NCBI Gene ID | 64167 ncbi.nlm.nih.gov/gene/64167 |
| Ensembl ID | ENSG00000164308 |
| UniProt ID | Q6P179 |
| OMIM ID | 609497 |
| HGNC ID | 29499 |
| Aliases | LRAP, MGC10850 |
Description
ERAP2 encodes an aminopeptidase that trims N-terminal residues of peptides in the endoplasmic reticulum, optimizing them for binding to MHC class I molecules. It plays a critical role in antigen presentation and immune response. Genetic variants in ERAP2 have been associated with autoimmune diseases and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ankylosing spondylitis | Altered peptide trimming affects MHC class I presentation, influencing disease risk | GWAS and functional studies (PMID: 21743469) |
| Birdshot chorioretinopathy | ERAP2 variants affect peptide repertoire, contributing to autoimmune uveitis | GWAS (PMID: 24938718) |
| HIV-1 infection | ERAP2 expression levels influence viral antigen presentation and immune control | Expression QTL studies (PMID: 23817571) |
| Colorectal cancer | ERAP2 overexpression may alter tumor antigen presentation, affecting immune surveillance | Expression analysis (PMID: 24614024) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 20.3 | Medium |
| Spleen | 18.7 | Medium |
| Small intestine | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 10.1 | Low |
| Brain | 5.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.4 | High expression |
| K-562 | 18.9 | Medium expression |
| MCF7 | 12.3 | Medium expression |
| HepG2 | 8.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2248374 | SNV (G/A) | ~50% in Europeans | Creates a cryptic splice site leading to nonsense-mediated decay, reducing ERAP2 expression |
| rs2549782 | Missense (Lys528Arg) | ~40% in Europeans | Alters enzyme activity and substrate specificity |
| rs291601 | SNV (intronic) | ~30% in Asians | Associated with altered ERAP2 expression and disease risk |
Mutation functional classification
Loss of Function (LOF)
rs2248374 causes reduced ERAP2 protein levels due to nonsense-mediated decay, leading to loss of function in antigen processing.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; some variants may increase enzyme activity but are not classified as gain-of-function.
Dominant Negative (DN)
No evidence for dominant-negative effects; ERAP2 functions as a dimer, but no dominant-negative mutations are documented.
View complete mutation data：
Gene Ontology (GO)
| • aminopeptidase activity | • metalloexopeptidase activity |
| • peptide binding | • MHC class I peptide loading complex |
| • endoplasmic reticulum lumen | • proteolysis |
Pathways
• Antigen processing and presentation
• MHC class I antigen presentation
• Immune system
Protein Summary
ERAP2 is a 960-amino acid zinc-dependent aminopeptidase localized in the endoplasmic reticulum. It trims peptides to 8-9 residues for MHC class I loading. It forms heterodimers with ERAP1, enhancing peptide trimming efficiency. Its expression is regulated by genetic variants and interferon-gamma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERAP2 Knockout HEK293 Cell Line | EDC10309 | Human | 64167 | Details Get a Quote |
| ERAP2 Knockout A-549 Cell Line | EDJ-KQ24014 | Human | 64167 | Details Get a Quote |
| ERAP2 Knockout HCT 116 Cell Line | EDJ-KQ24015 | Human | 64167 | Details Get a Quote |
| ERAP2 Knockout HeLa Cell Line | EDJ-KQ24016 | Human | 64167 | Details Get a Quote |
