RARG
protein-codingretinoic acid receptor gamma, the group of Retinoic acid receptors
Gene summary
This gene encodes a retinoic acid receptor that belongs to the nuclear hormone receptor family. Retinoic acid receptors (RARs) act as ligand-dependent transcriptional regulators. When bound to ligands, RARs activate transcription by binding as heterodimers to the retinoic acid response elements (RARE) found in the promoter regions of the target genes. In their unbound form, RARs repress transcription of their target genes. RARs are involved in various biological processes, including limb bud development, skeletal growth, and matrix homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RARG variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000966.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 28 | 1 | 29 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 34 | 1 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000957.1 | 8 | MANE Select | |
| Ensembl | ENSP00000388510.2 | 8 | MANE Select | |
| RefSeq | NP_001036193.1 | 8 | Standard | |
| RefSeq | NP_001230659.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rarga | Danio rerio | Structure: pharyngeal arch 5 Quality: immature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NHR
- Nuclear Receptors
- Mesodermal Commitment Pathway
- Nuclear Receptors in Lipid Metabolism and Toxicity
- Vitamin A and Carotenoid Metabolism
Biological Process
- negative regulation of transcription by RNA polymerase II
- neural tube closure
- glandular epithelial cell development
- growth plate cartilage chondrocyte growth
- transcription initiation from RNA polymerase II promoter
Molecular Function
- transcription regulatory region sequence-specific DNA binding
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- DNA-binding transcription factor activity
Cellular Component
- nuclear chromatin
- nucleus
- nucleoplasm
- transcription factor complex
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000425354
- Coding exons
- 8
- Length
- 22411
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125727
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 127 | 273 | 0.466 | 0.0000160 | 2969 |
| Missense (PolyPhen) | 31 | 121.86 | 0.2544 | 1238 | ||
| Synonymous | 0.297 | 104 | 108 | 0.964 | 0.00000610 | 909 |
| Loss of Function | 3.94 | 1 | 20.0 | 0.0500 | 0.00000116 | 217 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00017 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000028 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.221
Intolerance Scores
- LoFtool
- 0.0555
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |