HLA-DMA: Major Histocompatibility Complex, Class II, DM Alpha
A key regulator of antigen presentation and peptide loading in the immune system
Gene Information Card
| Symbol | HLA-DMA |
|---|---|
| Full Name | Major Histocompatibility Complex, Class II, DM Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.32 |
| NCBI Gene ID | 3108 ncbi.nlm.nih.gov/gene/3108 |
| Ensembl ID | ENSG00000204257 |
| UniProt ID | P28067 |
| OMIM ID | 142855 |
| HGNC ID | 4934 |
| Aliases | D6S222E, RING6 |
Description
HLA-DMA encodes the alpha chain of the HLA-DM heterodimer, a non-classical MHC class II molecule. HLA-DM is localized in endosomal/lysosomal compartments and functions as a peptide editor, facilitating the exchange of CLIP (class II-associated invariant chain peptide) with antigenic peptides on classical MHC class II molecules (HLA-DR, -DQ, -DP). This process is essential for proper antigen presentation and T-cell activation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | HLA-DMA polymorphisms may alter peptide loading efficiency, affecting autoantigen presentation and T-cell response. | OMIM 142855; NCBI Gene 3108 |
| Type 1 Diabetes | Variants in HLA-DMA are associated with altered MHC class II antigen presentation, contributing to autoimmune beta-cell destruction. | OMIM 142855; NCBI Gene 3108 |
| Celiac Disease | HLA-DMA expression levels influence gluten peptide presentation by HLA-DQ2/DQ8, modulating disease risk. | OMIM 142855; NCBI Gene 3108 |
| Multiple Sclerosis | HLA-DMA polymorphisms linked to altered antigen presentation in the central nervous system. | OMIM 142855; NCBI Gene 3108 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Lung | 6.1 | Low |
| Small intestine | 5.4 | Low |
| Whole blood | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocyte (GM12878) | 15.3 | High expression |
| Monocyte (THP-1) | 12.1 | Medium expression |
| Dendritic cell (immature) | 14.7 | High expression |
| T-cell (Jurkat) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1061808 (G>A) | SNP | 0.15 (global) | May affect HLA-DM stability and peptide loading efficiency |
| rs12722051 (C>T) | SNP | 0.08 (European) | Associated with altered autoimmune disease risk |
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of start codon; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Homozygous loss-of-function mutations in HLA-DMA are extremely rare but would impair CLIP removal, leading to defective antigen presentation and immunodeficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HLA-DMA.
Dominant Negative (DN)
Dominant-negative effects are not documented; however, heterozygous missense variants could theoretically disrupt HLA-DM dimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Antigen processing and presentation (KEGG hsa04612)
• Endosomal/Vacuolar pathway (Reactome R-HSA-2132295)
Protein Summary
HLA-DMA is the alpha subunit of the HLA-DM heterodimer, a non-polymorphic MHC class II molecule. It is composed of two extracellular domains (α1 and α2) and a transmembrane region. HLA-DM resides in late endosomes and lysosomes, where it catalyzes the removal of CLIP from classical MHC class II molecules and facilitates the binding of high-affinity antigenic peptides. This editing function is crucial for selecting immunodominant epitopes and shaping the CD4+ T-cell repertoire.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HLA-DMA Knockout HEK293 Cell Line | EDJ-KQ4870 | Human | 3108 | Details Get a Quote |
| HLA-DMA Knockout HeLa Cell Line | EDJ-KQ26447 | Human | 3108 | Details Get a Quote |
| HLA-DMA Knockout A-549 Cell Line | EDJ-KQ27658 | Human | 3108 | Details Get a Quote |
| HLA-DMA Knockout HCT 116 Cell Line | EDJ-KQ27659 | Human | 3108 | Details Get a Quote |
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