HLA-DMA
protein-codingmajor histocompatibility complex, class II, DM alpha, the group of Histocompatibility complex|C1-set domain containing
Gene summary
HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HLA-DMA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006120.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 6 | 6 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 6 | 1 | 1 | 8 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006111.2 | 5 | MANE Select | |
| Ensembl | ENSP00000363976.4 | 5 | MANE Select | |
| Ensembl | ENSP00000378714.3 | 5 | Standard | |
| Ensembl | ENSP00000378714.3 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antigen processing and presentation - Homo sapiens (human)
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Type I diabetes mellitus - Homo sapiens (human)
- Allograft rejection - Homo sapiens (human)
- Graft-versus-host disease - Homo sapiens (human)
Biological Process
- peptide antigen assembly with MHC class II protein complex
- immune response
- antigen processing and presentation of exogenous peptide antigen via MHC class II
Molecular Function
- MHC class II protein complex binding
Cellular Component
- lysosomal membrane
- cell surface
- membrane
- integral component of membrane
- late endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374843
- Coding exons
- 5
- Length
- 20482
- Individuals with no LoFs
- 123753
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 123760
- p
- 0.0000283
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.879 | 116 | 146 | 0.795 | 0.00000827 | 1703 |
| Missense (PolyPhen) | 33 | 53.538 | 0.61638 | 662 | ||
| Synonymous | 0.485 | 57 | 61.9 | 0.921 | 0.00000396 | 529 |
| Loss of Function | 1.61 | 6 | 12.0 | 0.498 | 5.19e-7 | 126 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000055 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000092 | 0.0000090 | rare |
| South Asian | 0.000066 | 0.000066 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. {ECO:0000269|PubMed:16547258, ECO:0000269|PubMed:8849454, ECO:0000269|PubMed:9768757}.;
Recessive Scores
- pRec
- 0.0950
Intolerance Scores
- LoFtool
- 0.306
- RVIS EVS
- 0.75
- RVIS percentile EVS
- 86.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.576
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |