NR1I2

Chr 3

nuclear receptor subfamily 1 group I member 2

Also known as: BXR, ONR1, PAR, PAR1, PAR2, PARq, PRR, PXR

This gene product belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 1.17
Clinical SummaryNR1I2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 VUS of 86 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.17LOEUF
pLI 0.000
Z-score 0.98
OE 0.76 (0.511.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.62Z-score
OE missense 1.11 (1.011.22)
307 obs / 277.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.76 (0.511.17)
00.351.4
Missense OE?1.11 (1.011.22)
00.61.4
Synonymous OE?1.13
01.21.6
LoF obs/exp: 15 / 19.7Missense obs/exp: 307 / 277.8Syn Z: -1.06

This gene — mechanism propensity

DN
0.6356th %ile
GOF
0.4677th %ile
LOF
0.4137th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

86 submitted variants in ClinVar

Classification Summary

VUS70
Likely Benign5
Benign5
70
VUS
5
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
70
0
0
70
Likely Benign
0
2
0
3
5
Benign
0
0
0
5
5
Total0720880

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap NR1I2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NR1I2 · protein map & ClinVar variants

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