NR4A1
protein-codingnuclear receptor subfamily 4 group A member 1, the group of Nuclear receptor subfamily 4 group A
Gene summary
This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
- HMR
- GFRP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.7 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 NR4A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173157.3. 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 | 5 | 4 | 3 | 12 | ||
| missense | 64 | 1 | 65 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 69 | 4 | 4 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775180.1 | 6 | MANE Select | |
| Ensembl | ENSP00000378302.1 | 6 | MANE Select | |
| RefSeq | NP_001189162.1 | 7 | Standard | |
| RefSeq | NP_001189163.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Cortisol synthesis and secretion - Homo sapiens (human)
- Aldosterone synthesis and secretion - Homo sapiens (human)
- Cushing,s syndrome - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
Biological Process
- positive regulation of endothelial cell proliferation
- cell migration involved in sprouting angiogenesis
- transcription initiation from RNA polymerase II promoter
- signal transduction
- intracellular receptor signaling pathway
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- cytosol
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360284
- Coding exons
- 7
- Length
- 36676
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125745
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.51 | 289 | 371 | 0.779 | 0.0000230 | 3872 |
| Missense (PolyPhen) | 113 | 171.48 | 0.65897 | 1862 | ||
| Synonymous | 0.179 | 166 | 169 | 0.982 | 0.0000110 | 1325 |
| Loss of Function | 3.38 | 5 | 22.2 | 0.225 | 0.00000112 | 252 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000066 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000081 | 0.000079 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'- AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. Plays a role in the vascular response to injury (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12813, ECO:0000269|PubMed:15466594, ECO:0000269|PubMed:22983157}.;
Recessive Scores
- pRec
- 0.624
Intolerance Scores
- LoFtool
- 0.0558
- RVIS EVS
- -1.24
- RVIS percentile EVS
- 5.41
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 |