RHO
Chr 3ADARrhodopsin
Also known as: CSNBAD1, OPN2, RP4
The protein encoded by this gene is found in rod cells in the back of the eye and is essential for vision in low-light conditions. The encoded protein binds to 11-cis retinal and is activated when light hits the retinal molecule. Defects in this gene are a cause of congenital stationary night blindness. [provided by RefSeq, Aug 2017]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-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.
References
ClinVar Variant Classifications
664 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 | 27 | 59 | 0 | 0 | 86 |
Likely Pathogenic | 28 | 86 | 0 | 0 | 114 |
VUS | 7 | 213 | 41 | 8 | 269 |
Likely Benign | 0 | 5 | 35 | 87 | 127 |
Benign | 0 | 2 | 16 | 3 | 21 |
Conflicting | — | 46 | |||
| Total | 62 | 365 | 92 | 98 | 663 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap RHO — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
RHO · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Natural History Study in Patients With PDE6A-, PDE6B- and RHO-linked Retinitis Pigmentosa
ACTIVE NOT RECRUITINGA Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
ACTIVE NOT RECRUITINGStudy to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
ACTIVE NOT RECRUITINGA Study of Oral MBQ-167 in Participants With Advanced Breast Cancer
RECRUITINGVSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Stage IV or Recurrent Endometrial Cancer
ACTIVE NOT RECRUITINGA Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
ACTIVE NOT RECRUITINGA Vaccine (VSV-hIFNβ-NIS) With or Without Cyclophosphamide and Combinations of Ipilimumab, Nivolumab, and Cemiplimab in Treating Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma
RECRUITINGPromising ROd-cone DYstrophy Gene therapY
ACTIVE NOT RECRUITINGSafety and Efficacy of ZVS203e in the Treatment of Retinitis Pigmentosa Caused by RHO Gene Mutation
RECRUITINGGVB-2001 Gene Therapy Via Intracameral Injection for the Treatment of Primary Open Angle Glaucoma
RECRUITINGProspective Natural History Study of Retinitis Pigmentosa
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools