RARB
Chr 3ADARretinoic acid receptor beta
Also known as: HAP, MCOPS12, NR1B2, RARbeta, RARbeta1, RRB2
This gene encodes retinoic acid receptor beta, a nuclear transcriptional regulator that binds retinoic acid (vitamin A) and forms heterodimers to regulate gene expression during embryonic development, cell growth, and differentiation. Mutations cause syndromic microphthalmia 12 with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI 0.9998, LOEUF 0.12), indicating that complete loss of protein function is typically incompatible with normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). 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.
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.
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
192 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 | 3 | 3 | 18 | 0 | 24 |
Likely Pathogenic | 5 | 16 | 1 | 0 | 22 |
VUS | 12 | 52 | 8 | 0 | 72 |
Likely Benign | 0 | 6 | 10 | 11 | 27 |
Benign | 0 | 2 | 18 | 3 | 23 |
Conflicting | — | 3 | |||
| Total | 20 | 79 | 55 | 14 | 171 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RARB · 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