NR1D2
Chr 3nuclear receptor subfamily 1 group D member 2
Also known as: BD73, EAR-1R, REVERBB, REVERBbeta, RVR
NR1D2 encodes a transcriptional repressor that coordinates circadian rhythms and metabolic pathways by forming a critical negative limb of the circadian clock and regulating genes involved in lipid metabolism and inflammatory responses. Mutations in NR1D2 cause familial advanced sleep phase, an autosomal dominant circadian rhythm disorder characterized by very early sleep and wake times. The gene shows high constraint against loss-of-function variants (LOEUF 0.621), reflecting its important role in circadian regulation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
110 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 20 | 0 | 20 |
Likely Pathogenic | 0 | 1 | 0 | 0 | 1 |
VUS | 0 | 65 | 1 | 0 | 66 |
Likely Benign | 0 | 3 | 0 | 1 | 4 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 69 | 21 | 2 | 92 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NR1D2 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools