NR4A1

nuclear receptor subfamily 4 group A member 1, the group of Nuclear receptor subfamily 4 group A

Basic information

Region (hg38): 12:52022831-52059507

Previous symbols: [ "HMR", "GFRP1" ]

Links

ENSG00000123358 ∙ NCBI:3164 ∙ OMIM:139139 ∙ HGNC:7980 ∙ Uniprot:P22736 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NR4A1 gene.

• Inborn genetic diseases (15 variants)
• not provided (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR4A1 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				4	3	7
missense			15		1	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding						0
Total	0	0	15	4	4

Variants in NR4A1

This is a list of pathogenic ClinVar variants found in the NR4A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-52054400-C-T			Benign (Aug 28, 2018)
12-52054441-C-T		not specified	Uncertain significance (Jan 26, 2022)
12-52054448-C-T			Benign (Aug 28, 2018)
12-52054449-G-C		not specified	Uncertain significance (Sep 26, 2023)
12-52054565-C-A			Likely benign (Jun 13, 2018)
12-52054579-C-T		not specified	Uncertain significance (Jan 24, 2024)
12-52054756-C-T		not specified	Uncertain significance (Feb 28, 2023)
12-52054815-C-T		not specified	Uncertain significance (Oct 26, 2022)
12-52054876-C-T		not specified	Uncertain significance (Jul 09, 2021)
12-52054916-C-T			Benign (Jul 16, 2018)
12-52054981-T-G		not specified	Uncertain significance (Oct 26, 2022)
12-52055011-C-T		not specified	Uncertain significance (Jan 04, 2022)
12-52055099-C-T			Likely benign (Mar 30, 2018)
12-52056023-C-A			Likely benign (Aug 16, 2018)
12-52056023-C-T			Benign (Dec 31, 2019)
12-52056057-A-G		not specified	Uncertain significance (Sep 17, 2021)
12-52056107-C-T			Likely benign (Jan 19, 2018)
12-52056139-C-T		not specified	Uncertain significance (Jul 27, 2022)
12-52057097-C-T		not specified	Uncertain significance (May 08, 2023)
12-52057119-C-T			Likely benign (Apr 10, 2018)
12-52057151-G-A			Benign (Dec 31, 2019)
12-52057205-A-G		not specified	Uncertain significance (Oct 29, 2021)
12-52057379-C-G		not specified	Uncertain significance (Sep 16, 2021)
12-52057405-G-A		not specified	Uncertain significance (Dec 13, 2022)
12-52057419-C-T		not specified	Uncertain significance (Sep 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR4A1	protein_coding	protein_coding	ENST00000360284	7	36676

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.371	0.629	125728	0	17	125745	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	289	371	0.779	0.0000230	3872
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000655	0.0000615
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000807	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.000170	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);NHR;Nuclear Receptors;Corticotropin-releasing hormone signaling pathway;Spinal Cord Injury;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;HDAC6 interactions;Disease;Signal Transduction;Gene expression (Transcription);role of mef2d in t-cell apoptosis;Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;AKT phosphorylates targets in the nucleus;Glucocorticoid receptor regulatory network;PIP3 activates AKT signaling;RXR and RAR heterodimerization with other nuclear receptor;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Intracellular signaling by second messengers;Diseases of signal transduction;Role of Calcineurin-dependent NFAT signaling in lymphocytes (Consensus)

Recessive Scores

• pRec: 0.624

Intolerance Scores

• loftool: 0.0558
• rvis_EVS: -1.24
• rvis_percentile_EVS: 5.41

Haploinsufficiency Scores

• pHI: 0.293
• hipred: Y
• hipred_score: 0.775
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nr4a1
• 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal 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); reproductive system phenotype

Gene ontology

• 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;endothelial cell chemotaxis;cellular response to vascular endothelial growth factor stimulus;steroid hormone mediated signaling pathway;cellular response to fibroblast growth factor stimulus;fat cell differentiation;negative regulation of cell cycle;positive regulation of transcription by RNA polymerase II;regulation of type B pancreatic cell proliferation;cellular response to corticotropin-releasing hormone stimulus
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytosol;nuclear membrane
• 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;steroid hormone receptor activity;nuclear receptor activity;protein binding;zinc ion binding;glucocorticoid receptor binding;sequence-specific DNA binding;protein heterodimerization activity