NR3C1
Chr 5ADnuclear receptor subfamily 3 group C member 1
Also known as: GCCR, GCR, GCRST, GR, GRL
The glucocorticoid receptor functions as a transcription factor that binds to glucocorticoid response elements to regulate gene expression and modulates other transcription factors, affecting inflammatory responses, cellular proliferation, and differentiation. Mutations cause glucocorticoid resistance with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
NR3C1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Growing Up in Multifactorial Risk Conditions
ENROLLING BY INVITATIONEffect of Transcranial Alternative Current Stimulation at Alpha Frequency (α-tACS) on Stressed Healthy Subjects
RECRUITINGFertility And Sexual Function In CAH: CALLIOPE
RECRUITINGContinuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants
RECRUITINGDiesel Exhaust Induces Glucocorticoid Resistance
RECRUITINGStudy of the Steroid Hormone Milieu in Obese Patients
RECRUITINGParaphilic Disorders and Other Conditions With Risk for Sexual Violence: a Case-control Study
RECRUITINGMaternal Characteristics Associated With Child Growth and Adiposity
RECRUITINGEffects of "Vitamin N" Nature Immersion Therapy on Stress Levels in Health Care Workers in the City of Bogotá
ACTIVE NOT RECRUITINGMultisensory Early Oral Administration of Human Milk (M-MILK) for Very Preterm Infants
RECRUITINGReality-monitoring & Stress
RECRUITINGExternal Resources
Links to major genomics databases and tools