{"entity":{"id":"rara","kind":"target","name":"Retinoic acid receptor alpha (RARA)","aka":[],"tldr":"The retinoic acid receptor that, fused to PML in acute promyelocytic leukaemia, blocks white blood cells from maturing. All-trans retinoic acid releases the block and arsenic trioxide destroys the fusion protein, turning a once rapidly fatal leukaemia into one of the most curable.","summary":"RARA is a nuclear receptor that switches on genes of myeloid differentiation when bound by retinoic acid. In acute promyelocytic leukaemia the t(15;17) translocation fuses PML to RARA, and the fusion protein recruits co-repressors that lock promyelocytes in an immature state. Pharmacological doses of all-trans retinoic acid (tretinoin) release the co-repressors and force differentiation, while arsenic trioxide binds the PML moiety and triggers degradation of the fusion protein. Given together, without chemotherapy in standard-risk disease, they cure most patients; differentiation syndrome is the characteristic early complication.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Retinoic_acid_receptor_alpha","links":[{"label":"UniProt P10276: RARA","url":"https://www.uniprot.org/uniprotkb/P10276/entry"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["tretinoin-atra","arsenic-trioxide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"RARA","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"one-type","specificityNote":"Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 4 medicines aimed at it (Tretinoin (all-trans retinoic acid, ATRA), Arsenic trioxide, Acitretin and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA RARA: RNA low tissue specificity; no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 2 specific cancer types at or above 0.5 (acute promyelocytic leukemia, acute myeloid leukemia); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas RARA tissue","url":"https://www.proteinatlas.org/ENSG00000131759-RARA/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000131759 associations","url":"https://platform.opentargets.org/target/ENSG00000131759/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9864","ensembl":"ENSG00000131759","uniprot":"P10276","entrez":"5914","firstDescribed":1987,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Giguere et al, Nature, 1987, \"Identification of a receptor for the morphogen retinoic acid\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2825036/","biology":"Ligand-activated nuclear receptor of myeloid differentiation; the PML::RARA fusion in APL is the drug target of tretinoin and arsenic trioxide.","whereFound":["Acute promyelocytic leukaemia (PML::RARA fusion in almost all cases)"],"targetClass":"nuclear-receptor","prevalence":[{"cancerId":"aml","pct":"about 10","measure":"PML::RARA fusion (acute promyelocytic leukaemia subtype)","source":"https://doi.org/10.1038/nrc2943","note":"PML::RARA is present in nearly all cases of acute promyelocytic leukaemia"}]},"route":"/targets/rara/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"apl","kind":"cancer","name":"Acute promyelocytic leukaemia","route":"/cancers/apl/"}],"drug":[{"id":"acitretin","kind":"drug","name":"Acitretin","route":"/drugs/acitretin/"},{"id":"arsenic-trioxide","kind":"drug","name":"Arsenic trioxide","route":"/drugs/arsenic-trioxide/"},{"id":"isotretinoin","kind":"drug","name":"Isotretinoin","route":"/drugs/isotretinoin/"},{"id":"tretinoin-atra","kind":"drug","name":"Tretinoin (all-trans retinoic acid, ATRA)","route":"/drugs/tretinoin-atra/"}]}}