NR4A1

Chr 12

nuclear receptor subfamily 4 group A member 1

Also known as: GFRP1, HMR, N10, NAK-1, NGFIB, NP10, NUR77, TR3

NCBI Gene: 3164ENSG00000123358UniProt: P22736

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]

GeneReviewsResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
12
Active trials
274
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.47
LOEUF
—
Mechanism
📖
GeneReview available — NR4A1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.47LOEUF
pLI 0.371
Z-score 3.38
OE 0.23 (0.12–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.51Z-score
OE missense 0.78 (0.71–0.86)
289 obs / 371.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.23 (0.12–0.47)
0≤0.351.4
Missense OE?0.78 (0.71–0.86)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 5 / 22.2Missense obs/exp: 289 / 371.0Syn Z: 0.18

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NR4A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer (Early Breast Cancer)Breast Cancer SurvivorsBreast Cancer Prognostic

Real-life Evaluation of Endopredict® in Early HR+/HER2- Breast Cancer

RECRUITING
NCT07379918Assistance Publique - Hôpitaux de ParisStarted 2026-06-28
Endopredict test
HER2-positive Breast Cancer

Identification of Risk Factors for Brain Recurrence in Patients With HER2-positive Localised Breast Cancer

RECRUITING
NCT06358625Center Eugene MarquisStarted 2024-06-06
Pre-treatment biopsy
Anatomic Stage IV Breast Cancer AJCC v8Hormone Receptor Positive Breast CarcinomaMetastatic Breast Carcinoma

Using FDG-PET/CT to Assess Response of Bone-Dominant Metastatic Breast Cancer, FEATURE Study

ACTIVE NOT RECRUITING
NCT04316117Phase PHASE2ECOG-ACRIN Cancer Research GroupStarted 2020-09-15
Computed TomographyFludeoxyglucose F-18Positron Emission Tomography
Breast CancerBreast NeoplasmsHormone Receptor Positive Tumor

Establishment of Molecular Profiling for Individual Clinical Routine Treatment Decision in Early Breast Cancer

ACTIVE NOT RECRUITING
NCT03904173Oslo University HospitalStarted 2018-10-29
Multi-parameter tests
Breast CancerMetastatic Breast CancermiRNAs

PTEN and Organ-Specific microRNAs in Metastatic Breast Cancer

RECRUITING
NCT07297134Atlas UniversityStarted 2025-12-01
Breast CancerHER-2 Positive Breast Cancer

Gut Microbiome Changes During Abemaciclib Therapy in Breast Cancer

NOT YET RECRUITING
NCT07406594Phase NAUniversity of Vermont Medical CenterStarted 2027-10
Resistant Potato StarchPlacebo control
Breast CancerHER2-negative Breast CancerHormone Receptor Positive Tumor

Elacestrant With/Without Triptorelin in Premenopausal Women With Luminal Breast Cancer

RECRUITING
NCT05982093Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2023-02-03
ElacestrantTriptorelinTamoxifen 20 mg
Acute Myeloid LeukemiaAnatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8

National Cancer Institute "Cancer Moonshot Biobank"

ACTIVE NOT RECRUITING
NCT04314401National Cancer Institute (NCI)Started 2020-11-11
Biospecimen CollectionComputed TomographyMagnetic Resonance Imaging
NSCLCSCLCHigh Grade Neuroendocrine Cancer

Study of Oral MRT-2359 in Selected Cancer Patients

ACTIVE NOT RECRUITING
NCT05546268Phase PHASE1, PHASE2Monte Rosa Therapeutics, IncStarted 2022-10-12
Oral MRT-2359Oral MRT-2359Oral MRT-2359
Acupuncture TreatmentHormone Receptor-Positive Breast CancerHot Flashes

A Randomized Controlled Trial of Acupuncture for the Management of Hot Flashes in Patients With Hormone Receptor-Positive Breast Cancer

NOT YET RECRUITING
NCT07294339Phase NAPeking University People's HospitalStarted 2026-04-01
True AcupunctureSham Acupuncture
Breast Cancer

Omega 3 Fatty Acids and ERPR(-)HER2(+/-) Breast Cancer Prevention

ACTIVE NOT RECRUITING
NCT02295059Phase NACity of Hope Medical CenterStarted 2017-08-09
omega 3 fatty acids
Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8

Monitoring Symptoms to Help Young Women Take Hormone Therapy for Stage I-III Breast Cancer, ASPEN Study

ACTIVE NOT RECRUITING
NCT05568472Phase NASWOG Cancer Research NetworkStarted 2023-03-29
Best PracticeBiospecimen CollectionEndocrine Drug Therapy

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients