RORA: Retinoic Acid Receptor-Related Orphan Receptor Alpha
Nuclear receptor involved in circadian rhythm, metabolism, and neurodevelopment
Gene Information Card
| Symbol | RORA |
|---|---|
| Full Name | RAR-related orphan receptor A |
| Gene Type | protein-coding |
| Chromosomal Location | 15q22.2 |
| NCBI Gene ID | 6095 ncbi.nlm.nih.gov/gene/6095 |
| Ensembl ID | ENSG00000069667 |
| UniProt ID | P35398 |
| OMIM ID | 600825 |
| HGNC ID | 10258 |
| Aliases | ROR1, ROR2, ROR3, NR1F1 |
Description
The RORA gene encodes a member of the NR1 subfamily of nuclear hormone receptors. The protein is a DNA-binding transcription factor that regulates gene expression involved in circadian rhythm, cerebellar development, lipid metabolism, and immune response. RORA binds as a monomer to ROR response elements (ROREs) and is modulated by oxysterols. Alternative splicing generates multiple isoforms with distinct tissue-specific functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal dominant cerebellar ataxia with mental retardation | Loss of RORA function in cerebellar Purkinje cells impairs motor coordination | OMIM #618060; ClinVar pathogenic variants |
| Susceptibility to asthma | RORA polymorphisms affect Th2 cytokine regulation and airway inflammation | GWAS studies; ClinVar risk alleles |
| Circadian rhythm sleep disorders | RORA dysregulation alters clock gene expression (e.g., BMAL1, CLOCK) | Functional studies; animal models |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 12.5 | High |
| Adipose tissue | 8.3 | Medium |
| Liver | 6.1 | Medium |
| Skeletal muscle | 4.7 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.2 | Neuronal model; high expression |
| HepG2 (hepatocellular carcinoma) | 7.8 | Hepatic metabolism studies |
| A549 (lung carcinoma) | 5.4 | Respiratory epithelial model |
| MCF7 (breast adenocarcinoma) | 3.1 | Hormone-responsive cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1075C>T (p.Arg359*) | Nonsense | <0.01% | Premature truncation; loss of DNA-binding domain |
| c.1340G>A (p.Arg447Gln) | Missense | <0.01% | Reduced transcriptional activity; associated with ataxia |
| c.1661_1662del (p.Glu554Valfs*12) | Frameshift | <0.01% | Loss of C-terminal activation domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated protein lacking functional domains, resulting in haploinsufficiency or complete loss of transcriptional activity.
Gain of Function (GOF)
Not reported in RORA.
Dominant Negative (DN)
Missense mutations in the ligand-binding domain may interfere with wild-type RORA function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Circadian entrainment (KEGG hsa04713)
• Nuclear receptor transcription pathway (Reactome R-HSA-383280)
• RORA activates gene expression (Reactome R-HSA-1368082)
Protein Summary
RORA is a 556-amino acid nuclear receptor with an N-terminal DNA-binding domain (DBD) containing two zinc fingers, a hinge region, and a C-terminal ligand-binding domain (LBD). It functions as a monomer to regulate transcription of target genes such as BMAL1, REV-ERBα, and SREBP-1c. The protein is highly expressed in the cerebellum, where it is essential for Purkinje cell survival and motor coordination. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RORA Knockout HEK293 Cell Line | EDJ-KQ2056 | Human | 6095 | Details Get a Quote |
| RORA Knockout A-549 Cell Line | EDJ-KQ22116 | Human | 6095 | Details Get a Quote |
| RORA Knockout HeLa Cell Line | EDJ-KQ54335 | Human | 6095 | Details Get a Quote |
| RORA Knockout HCT 116 Cell Line | EDJ-KQ71295 | Human | 6095 | Details Get a Quote |
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