NR4A3
nuclear receptor subfamily 4 group A member 3, the group of Nuclear receptor subfamily 4 group A
Basic information
Region (hg38): 9:99821855-99866891
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR4A3 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 14 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 2 | 0 |
Variants in NR4A3
This is a list of pathogenic ClinVar variants found in the NR4A3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-99828074-C-T | not specified | Uncertain significance (May 05, 2023) | ||
| 9-99828077-C-T | not specified | Uncertain significance (Jan 03, 2024) | ||
| 9-99828190-A-G | not specified | Uncertain significance (Oct 14, 2023) | ||
| 9-99828440-T-C | not specified | Uncertain significance (Apr 09, 2024) | ||
| 9-99828461-C-T | not specified | Uncertain significance (Jan 30, 2024) | ||
| 9-99828473-C-G | not specified | Uncertain significance (Dec 18, 2023) | ||
| 9-99828487-C-T | not specified | Uncertain significance (Oct 12, 2022) | ||
| 9-99828513-C-G | not specified | Uncertain significance (Mar 15, 2024) | ||
| 9-99828656-C-G | not specified | Uncertain significance (May 04, 2023) | ||
| 9-99828708-C-G | not specified | Uncertain significance (May 31, 2023) | ||
| 9-99828752-C-A | not specified | Uncertain significance (Aug 21, 2023) | ||
| 9-99828773-G-T | not specified | Uncertain significance (Jun 17, 2024) | ||
| 9-99833288-G-A | not specified | Uncertain significance (Apr 07, 2022) | ||
| 9-99833356-C-T | not specified | Uncertain significance (Nov 09, 2021) | ||
| 9-99833386-A-G | not specified | Likely benign (Dec 02, 2022) | ||
| 9-99847429-C-A | Likely benign (Jul 26, 2018) | |||
| 9-99847497-G-C | not specified | Uncertain significance (Mar 15, 2024) | ||
| 9-99847505-G-A | not specified | Uncertain significance (Oct 25, 2022) | ||
| 9-99847529-C-A | not specified | Uncertain significance (Jan 19, 2024) | ||
| 9-99863668-A-C | not specified | Uncertain significance (May 03, 2023) | ||
| 9-99863739-G-C | not specified | Likely benign (Oct 04, 2022) | ||
| 9-99863758-G-A | not specified | Uncertain significance (Mar 26, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NR4A3 | protein_coding | protein_coding | ENST00000330847 | 7 | 45037 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.913 | 0.0874 | 125742 | 0 | 6 | 125748 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.81 | 186 | 329 | 0.565 | 0.0000179 | 4095 |
| Missense in Polyphen | 40 | 115.89 | 0.34514 | 1346 | ||
| Synonymous | 1.70 | 118 | 144 | 0.820 | 0.00000858 | 1301 |
| Loss of Function | 3.94 | 4 | 25.5 | 0.157 | 0.00000141 | 286 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000580 | 0.0000580 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000464 | 0.0000462 |
| European (Non-Finnish) | 0.0000265 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity). Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (By similarity). {ECO:0000250|UniProtKB:P51179, ECO:0000250|UniProtKB:Q9QZB6, ECO:0000269|PubMed:20558821, ECO:0000269|PubMed:24022864}.;
- Disease
- DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving NR4A3 is found in patients with Erwing sarcoma. Translocation t(9;22)(q22- 31;q11-12) with EWSR1.; DISEASE: Note=A chromosomal aberration involving NR4A3 is a cause of a form of extraskeletal myxoid chondrosarcomas (EMC). Translocation t(9;17)(q22;q11) with TAF2N.;
- Pathway
- Transcriptional misregulation in cancer - Homo sapiens (human);NHR;VEGFA-VEGFR2 Signaling Pathway;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Hypertrophy Model;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Transcriptional regulation by RUNX1
(Consensus)
Recessive Scores
- pRec
- 0.184
Intolerance Scores
- loftool
- 0.0341
- rvis_EVS
- -0.34
- rvis_percentile_EVS
- 30.07
Haploinsufficiency Scores
- pHI
- 0.715
- hipred
- hipred_score
- ghis
- 0.433
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nr4a3
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; neoplasm; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype;
Zebrafish Information Network
- Gene name
- nr4a3
- Affected structure
- neutrophil
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;mesoderm formation;transcription initiation from RNA polymerase II promoter;gastrulation;axon guidance;pyruvate oxidation;positive regulation of cardiac muscle hypertrophy;positive regulation of glucose transmembrane transport;hippocampus development;intracellular receptor signaling pathway;adult behavior;animal organ regeneration;positive regulation of mast cell cytokine production;common myeloid progenitor cell proliferation;positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway;response to hydrogen peroxide;mast cell degranulation;steroid hormone mediated signaling pathway;negative regulation of neuron apoptotic process;cellular response to leptin stimulus;cellular respiration;fat cell differentiation;regulation of megakaryocyte differentiation;positive regulation of cell cycle;positive regulation of transcription by RNA polymerase II;positive regulation of fatty acid oxidation;platelet-derived growth factor receptor signaling pathway;regulation of smooth muscle cell proliferation;positive regulation of smooth muscle cell proliferation;semicircular canal morphogenesis;positive regulation of epithelial cell proliferation;neuromuscular process controlling balance;vestibular reflex;regulation of type B pancreatic cell proliferation;cellular response to corticotropin-releasing hormone stimulus;cellular response to catecholamine stimulus;energy homeostasis;positive regulation of monocyte aggregation;negative regulation of hydrogen peroxide-induced neuron death;positive regulation of vascular smooth muscle cell proliferation;positive regulation of vascular associated smooth muscle cell migration;positive regulation of leukocyte apoptotic process;positive regulation of feeding behavior
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;mast cell granule
- 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;transcription coactivator binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;steroid hormone receptor activity;nuclear receptor activity;protein binding;zinc ion binding;protein kinase binding;histone acetyltransferase binding;glucocorticoid receptor binding;cAMP response element binding;protein homodimerization activity;sequence-specific DNA binding