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]
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.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
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 |
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.