HLA-E: Major Histocompatibility Complex, Class I, E
A non-classical MHC class I molecule involved in immune regulation and NK cell recognition
Gene Information Card
| Symbol | HLA-E |
|---|---|
| Full Name | Major Histocompatibility Complex, Class I, E |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 3133 ncbi.nlm.nih.gov/gene/3133 |
| Ensembl ID | ENSG00000204592 |
| UniProt ID | P13747 |
| OMIM ID | 143010 |
| HGNC ID | 4934 |
| Aliases | EA1, EA2, HLA-6.2, MHC class I antigen E |
Description
HLA-E is a non-classical major histocompatibility complex (MHC) class I gene located on chromosome 6p21.33. It encodes a heavy chain that forms a heterodimer with beta-2-microglobulin. HLA-E is characterized by limited polymorphism and functions primarily by presenting leader peptides derived from other MHC class I molecules to natural killer (NK) cells via the CD94/NKG2 receptor complex, thereby regulating NK cell activity and immune surveillance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIV/AIDS | HLA-E polymorphisms influence NK cell-mediated control of HIV-1 replication | PMID: 23319692 |
| Preeclampsia | Altered HLA-E expression at the maternal-fetal interface may contribute to immune dysregulation | PMID: 26084822 |
| Cancer (various) | HLA-E overexpression on tumor cells inhibits NK cell cytotoxicity via CD94/NKG2A, promoting immune evasion | PMID: 25605246 |
| Autoimmune diseases (e.g., Behçet's disease) | HLA-E variants associated with altered NK cell regulation and disease susceptibility | PMID: 24919456 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Lung | 9.2 | Medium |
| Small intestine | 8.7 | Medium |
| Colon | 7.9 | Low |
| Kidney | 6.5 | Low |
| Liver | 4.3 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | Embryonic kidney cell line |
| HeLa | 12.1 | Cervical carcinoma cell line |
| K562 | 8.4 | Leukemia cell line |
| Jurkat | 7.6 | T-cell leukemia cell line |
| HepG2 | 5.2 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| HLA-E*01:01 | Allelic variant | Common | No known functional change; reference allele |
| HLA-E*01:03 | Allelic variant | Common | Increased cell surface expression compared to *01:01 |
| HLA-E*01:04 | Allelic variant | Rare | Reduced binding to CD94/NKG2A |
| rs1264457 (SNP) | Single nucleotide polymorphism | Variable | Associated with altered HLA-E expression and disease susceptibility |
Mutation functional classification
Loss of Function (LOF)
Rare variants that impair peptide binding or surface expression, reducing NK cell inhibition.
Gain of Function (GOF)
Not well characterized; increased expression variants (e.g., *01:03) may enhance immune evasion.
Dominant Negative (DN)
Not reported for HLA-E.
View complete mutation data：
Gene Ontology (GO)
| • antigen processing and presentation of exogenous peptide antigen via MHC class I (GO:0002474) | • antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0002486) |
| • signaling receptor binding (GO:0005102) | • immune response (GO:0006955) |
| • antigen processing and presentation (GO:0019882) | • MHC class I receptor activity (GO:0032395) |
| • peptide antigen binding (GO:0042605) | • MHC class I protein complex (GO:0042612) |
Pathways
• Antigen processing and presentation (KEGG hsa04612)
• Natural killer cell mediated cytotoxicity (KEGG hsa04650)
• Immune system (Reactome R-HSA-168256)
• MHC class I antigen presentation (Reactome R-HSA-983170)
Protein Summary
HLA-E is a non-classical MHC class I molecule that forms a heterodimer with beta-2-microglobulin. It has a restricted peptide-binding groove that preferentially accommodates leader peptides derived from other MHC class I molecules (e.g., HLA-A, -B, -C). The HLA-E/peptide complex is recognized by the CD94/NKG2 receptor family on NK cells and some T cells: binding to CD94/NKG2A delivers an inhibitory signal, while binding to CD94/NKG2C activates effector functions. This interaction is critical for NK cell education, immune tolerance, and tumor immune surveillance. HLA-E is broadly expressed in many tissues, with highest levels in lymphoid organs. Its limited polymorphism and functional role in immune regulation make it a target for therapeutic modulation in cancer, autoimmune diseases, and transplantation.
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