HLA-A
major histocompatibility complex, class I, A

HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

Member of: DE-9 Developmental clusters: GC2 GC3
Biological processes 75 terms
CD8 receptor binding (GO:0042610)CD8-positive, alpha-beta T cell activation (GO:0036037)ER to Golgi transport vesicle membrane (GO:0012507)ER to Golgi transport vesicle membrane (GO:0012507)Golgi apparatus (GO:0005794)Golgi medial cisterna (GO:0005797)Golgi membrane (GO:0000139)Golgi membrane (GO:0000139)MHC class I peptide loading complex (GO:0042824)MHC class I protein complex (GO:0042612)RNA binding (GO:0003723)T cell mediated cytotoxicity (GO:0001913)T cell mediated cytotoxicity directed against tumor cell target (GO:0002419)T cell receptor binding (GO:0042608)T cell receptor signaling pathway (GO:0050852)TAP binding (GO:0046977)TAP complex binding (GO:0062061)antibacterial humoral response (GO:0019731)antigen processing and presentation (GO:0019882)antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0019885)antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent (GO:0002485)antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent (GO:0002486)antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent (GO:0002486)antigen processing and presentation of endogenous peptide antigen via MHC class Ib (GO:0002476)antigen processing and presentation of exogenous peptide antigen via MHC class I (GO:0042590)antigen processing and presentation of exogenous peptide antigen via MHC class Ib (GO:0002477)beta-2-microglobulin binding (GO:0030881)beta-2-microglobulin binding (GO:0030881)beta-2-microglobulin binding (GO:0030881)beta-2-microglobulin binding (GO:0030881)cell surface (GO:0009986)cell surface (GO:0009986)defense response to Gram-positive bacterium (GO:0050830)detection of bacterium (GO:0016045)early endosome membrane (GO:0031901)early endosome membrane (GO:0031901)endoplasmic reticulum (GO:0005783)endoplasmic reticulum exit site (GO:0070971)endoplasmic reticulum membrane (GO:0005789)endoplasmic reticulum membrane (GO:0005789)external side of plasma membrane (GO:0009897)extracellular exosome (GO:0070062)extracellular region (GO:0005576)immune response (GO:0006955)immune response (GO:0006955)immune response (GO:0006955)immune response (GO:0006955)lumenal side of endoplasmic reticulum membrane (GO:0098553)lumenal side of endoplasmic reticulum membrane (GO:0098553)membrane (GO:0016020)peptide antigen assembly with MHC class I protein complex (GO:0002502)peptide antigen binding (GO:0042605)peptide antigen binding (GO:0042605)peptide antigen binding (GO:0042605)phagocytic vesicle membrane (GO:0030670)phagocytic vesicle membrane (GO:0030670)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)plasma membrane (GO:0005886)positive regulation of CD8-positive, alpha-beta T cell activation (GO:2001187)positive regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000566)positive regulation of T cell cytokine production (GO:0002726)positive regulation of T cell mediated cytotoxicity (GO:0001916)positive regulation of T cell mediated cytotoxicity (GO:0001916)positive regulation of memory T cell activation (GO:2000568)positive regulation of type II interferon production (GO:0032729)protection from natural killer cell mediated cytotoxicity (GO:0042270)protection from natural killer cell mediated cytotoxicity (GO:0042270)protein binding (GO:0005515)recycling endosome membrane (GO:0055038)recycling endosome membrane (GO:0055038)regulation of natural killer cell mediated immunity (GO:0002715)signaling receptor binding (GO:0005102)signaling receptor binding (GO:0005102)
Expression (TPM)
HLA-A — as a Regulated Gene

TFs regulating HLA-A 0 TFs

Transcription factors with Perturb-seq knockdown data for HLA-A. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = HLA-A upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to HLA-A

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of HLA-A, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr6:29,649,730–29,650,515 292.4 kb Distal (>10kb) Multiome 598
chr6:29,723,179–29,723,705 219.1 kb Distal (>10kb) Multiome 318
chr6:29,723,819–29,724,477 218.3 kb Distal (>10kb) Multiome 252
chr6:29,748,600–29,749,515 193.4 kb Distal (>10kb) Multiome 593
chr6:29,752,563–29,753,367 189.4 kb Distal (>10kb) Multiome 598
chr6:29,926,526–29,927,449 15.4 kb Distal (>10kb) Multiome 372
chr6:29,942,301–29,942,598 at TSS At TSS 279
chr6:30,006,934–30,007,571 64.7 kb Distal (>10kb) Multiome 195
chr6:30,060,737–30,061,999 118.7 kb Distal (>10kb) Multiome 973
chr6:30,066,588–30,067,716 124.6 kb Distal (>10kb) Multiome 952
chr6:30,101,800–30,102,573 159.6 kb Distal (>10kb) Multiome 644
chr6:30,103,094–30,103,626 160.8 kb Distal (>10kb) Multiome 616
chr6:30,171,597–30,172,574 229.4 kb Distal (>10kb) Multiome 185
chr6:30,207,044–30,207,811 264.8 kb Distal (>10kb) Multiome 514
chr6:30,212,953–30,213,888 270.9 kb Distal (>10kb) Multiome 826
chr6:30,213,977–30,214,728 272.1 kb Distal (>10kb) Multiome 758

Genome Browser

Genomic view of the HLA-A locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr6:29,639,730 – 30,224,728
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq