NR1I2

Chr 3

nuclear receptor subfamily 1 group I member 2

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

NCBI Gene: 8856 ENSG00000144852 UniProt: O75469 OMIM: 603065

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.000

Z-score 0.98

OE 0.76 (0.51–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.62Z-score

OE missense 1.11 (1.01–1.22)

307 obs / 277.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.51–1.17)

0≤0.351.4

Missense OE?1.11 (1.01–1.22)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 15 / 19.7Missense obs/exp: 307 / 277.8Syn Z: -1.06

Background carrier burden — how many people carry a rare variant somewhere in NR1I2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

649 rare PASS variants

Rare truncating (LoF)

1 in 1,200

118 rare PASS variants

Rare synonymous (reference)

1 in 130

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NR1I2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,200
South Asian	~43k	1 in 72	1 in 790
Remaining (unassigned)	~30k	1 in 62	1 in 1,400
European (Finnish)	~27k	1 in 480	1 in 3,800
Admixed American	~22k	1 in 58	≈ 1 in 7,300
African / African American	~21k	1 in 74	1 in 870
East Asian	~20k	1 in 94	1 in 1,400
Ashkenazi Jewish	~13k	1 in 370	none seen
Middle Eastern	~2,884	1 in 60	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓