RARA (Retinoic Acid Receptor Alpha)
Nuclear receptor involved in myeloid differentiation and acute promyelocytic leukemia
Gene Information Card
| Symbol | RARA |
|---|---|
| Full Name | Retinoic Acid Receptor Alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 5914 ncbi.nlm.nih.gov/gene/5914 |
| Ensembl ID | ENSG00000131759 |
| UniProt ID | P10276 |
| OMIM ID | 180240 |
| HGNC ID | 9864 |
| Aliases | NR1B1, RARalpha, RAR-alpha |
Description
The RARA gene encodes retinoic acid receptor alpha, a nuclear receptor that binds retinoic acid and regulates transcription of genes involved in cell differentiation, proliferation, and apoptosis. It forms heterodimers with RXR receptors and is critical for myeloid development. Chromosomal translocations involving RARA, most commonly t(15;17)(q24;q21) producing PML-RARA fusion, are causative for acute promyelocytic leukemia (APL).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Promyelocytic Leukemia (APL) | PML-RARA fusion protein blocks myeloid differentiation by recruiting co-repressors and preventing retinoic acid response | Strong: recurrent t(15;17) found in >95% of APL cases (OMIM #612376, COSMIC) |
| Acute Myeloid Leukemia (AML) with variant RARA fusions | Alternative fusions (e.g., ZBTB16-RARA, NPM1-RARA) disrupt RARA signaling | Strong: documented in rare APL variants (COSMIC, ClinVar) |
| Retinoic Acid Resistance | Point mutations in RARA ligand-binding domain (e.g., R394W) reduce ATRA binding | Moderate: reported in relapsed APL (ClinVar, literature) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 6.1 | Low |
| Testis | 15.2 | Medium |
| Lung | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (promyelocytic leukemia) | 18.4 | High expression; model for ATRA-induced differentiation |
| NB4 (APL with PML-RARA) | 22.1 | High expression; fusion protein present |
| K-562 (chronic myeloid leukemia) | 7.2 | Moderate expression |
| HEK293 (embryonic kidney) | 5.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| t(15;17)(q24;q21) | Chromosomal translocation | >95% in APL | PML-RARA fusion; blocks differentiation |
| R394W | Missense | <1% | Reduces ATRA binding; associated with resistance |
| L398P | Missense | <1% | Impaired ligand-dependent transactivation |
| G303E | Missense | <1% | Alters DNA binding domain function |
Mutation functional classification
Loss of Function (LOF)
RARA point mutations in the ligand-binding domain (e.g., R394W) reduce or abolish retinoic acid response, leading to loss of normal transcriptional activation.
Gain of Function (GOF)
PML-RARA fusion acts as a dominant oncoprotein that recruits co-repressors, but can be converted to a transcriptional activator by pharmacological doses of ATRA, representing a conditional gain-of-function.
Dominant Negative (DN)
PML-RARA and other RARA fusions (e.g., ZBTB16-RARA) suppress wild-type RARA signaling by competing for DNA binding and recruiting repressor complexes, acting as dominant-negative inhibitors of myeloid differentiation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Retinoic acid receptor signaling pathway (Reactome: R-HSA-9006931)
• Nuclear receptor transcription pathway (KEGG: hsa03320)
• Acute myeloid leukemia (KEGG: hsa05221)
• Transcriptional regulation by PML-RARA (Reactome: R-HSA-9615017)
Protein Summary
Retinoic acid receptor alpha (UniProt P10276) is a 462-amino-acid nuclear receptor with a central DNA-binding domain (two zinc fingers) and a C-terminal ligand-binding domain. It heterodimerizes with RXR and binds retinoic acid response elements (RAREs) to regulate gene expression. The PML-RARA fusion protein retains the DNA-binding and ligand-binding domains of RARA, leading to aberrant recruitment of co-repressors and blocked differentiation. ATRA therapy reverses this repression, inducing terminal differentiation of APL blasts.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RARA Knockout HEK293 Cell Line | EDJ-KQ17839 | Human | 5914 | Details Get a Quote |
| RARA Knockout A-549 Cell Line | EDJ-KQ25710 | Human | 5914 | Details Get a Quote |
| RARA Knockout HCT 116 Cell Line | EDJ-KQ25711 | Human | 5914 | Details Get a Quote |
| RARA Knockout HeLa Cell Line | EDJ-KQ25712 | Human | 5914 | Details Get a Quote |
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