RORB

Chr 9AD

RAR related orphan receptor B

Also known as: EIG15, NR1F2, ROR-BETA, RORbeta, RZR-BETA, RZRB, bA133M9.1

NCBI Gene: 6096ENSG00000198963UniProt: Q92753OMIM: 601972

RORB encodes a nuclear receptor that binds DNA to regulate gene transcription, particularly controlling photoreceptor development, circadian rhythm regulation, and neocortical neuron patterning. Mutations cause idiopathic generalized epilepsy with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.11), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.111 OMIM phenotype
Clinical Summary— RORB
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
0.11LOEUF
pLI 1.000
Z-score 4.78
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.08Z-score
OE missense 0.46 (0.39–0.53)
116 obs / 254.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.11)
0≤0.351.4
Missense OE0.46 (0.39–0.53)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 0 / 26.6Missense obs/exp: 116 / 254.4Syn Z: 0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRORB-related epilepsy and neurodevelopmental disorderOTHERAD
DN
0.3594th %ile
GOF
0.3292th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.11

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RORB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
LncRNA RORB-IT1 Encoding a Micropeptide Regulates Progesterone Synthesis, Proliferation and Apoptosis in Chicken Granulosa Cells.
Cao J et al.·Cells
2026Open Access
Transient Knockdown of RORB with Cell-Penetrating siRNA Improves Visual Function in a Proteotoxic Mouse Model of Retinitis Pigmentosa.
Son C et al.·Biomedicines
2025Open AccessFunctional
Targeting RBM10-Repressed RORB Activity in Liquid Condensates Inhibits Lysosomal Biogenesis and Neuroblastoma Progression via Affecting NF-κB Signaling.
Guo Y et al.·Adv Sci (Weinh)
2025Open Access
Case Report: A 3' splice site variation in RORB exon 3 associated with idiopathic generalized epilepsy in a child.
Shi D et al.·Front Genet
2024Open AccessCase report
Fe3O4 nanoparticles containing gambogic acid inhibit metastasis in colorectal cancer via the RORB/EMILIN1 axis.
Fan X et al.·Cell Adh Migr
2024Open Access
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