RXRA

Chr 9

retinoid X receptor alpha

Also known as: NR2B1, RXR-alpha, RXRalpha

NCBI Gene: 6256ENSG00000186350UniProt: P19793OMIM: 180245

The protein functions as a nuclear receptor that acts as a transcription factor, forming heterodimers with retinoic acid receptors and other nuclear receptors to regulate gene expression in response to retinoic acid and other ligands. Mutations cause a developmental disorder with intellectual disability, microcephaly, short stature, and distinctive facial features, inherited in an autosomal dominant pattern. This gene is extremely intolerant to loss-of-function variants, indicating that proper protein function is critical for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.16
Clinical Summary— RXRA
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Gene-Disease Validity (ClinGen)
congenital heart disease · UDNo Known Disease Relationship

No known disease relationship

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 30 VUS of 88 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 0.999
Z-score 4.04
OE 0.00 (0.00–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.97Z-score
OE missense 0.53 (0.46–0.60)
163 obs / 310.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.16)
0≤0.351.4
Missense OE0.53 (0.46–0.60)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 0 / 19.0Missense obs/exp: 163 / 310.1Syn Z: -0.29
DN
0.4785th %ile
GOF
0.3392th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

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

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS30
Likely Benign2
42
Pathogenic
2
Likely Pathogenic
30
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
1
1
0
2
VUS
1
24
5
0
30
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total12548276

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

View in ClinVar →

Protein Context — Lollipop Plot

RXRA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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