RHO

Chr 3ADAR

rhodopsin

Also known as: CSNBAD1, OPN2, RP4

NCBI Gene: 6010 ENSG00000163914 UniProt: P08100 OMIM: 180380

This G-protein coupled receptor in retinal rod cells binds 11-cis-retinal and undergoes light-induced conformational changes that activate phototransduction signaling essential for low-light vision. Mutations cause autosomal recessive congenital stationary night blindness and primary microcephaly 17, affecting both visual and neurodevelopmental systems. The gene shows tolerance to loss-of-function variants (pLI 0.0001, LOEUF 1.08), suggesting the pathogenic variants may have specific effects on protein function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Night blindness, congenital stationary, autosomal dominant 1MIM #610445

Retinitis pigmentosa 4, autosomal dominant or recessiveMIM #613731

ADAR

Retinitis punctata albescensMIM #136880

ADAR

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · RHO-related retinopathy · SD · ClinGen 2025

Interpreting a novel variant

The dominant disease is caused by dominant-negative changes and the recessive disease by loss of function (Gene2Phenotype). A single heterozygous truncating variant therefore fits the recessive disease and does not by itself explain a dominant presentation; a novel missense has to be read against the dominant mechanism.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

4470

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

Multiple*

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.35

OE 0.60 (0.35–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.95 (0.85–1.07)

209 obs / 219.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.35–1.08)

0≤0.351.4

Missense OE?0.95 (0.85–1.07)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 8 / 13.3Missense obs/exp: 209 / 219.1Syn Z: -1.35

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

440 rare PASS variants

Rare truncating (LoF)

1 in 3,400

52 rare PASS variants

Rare synonymous (reference)

1 in 110

220 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RHO. 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 150	1 in 3,400
South Asian	~43k	1 in 93	1 in 5,400
Remaining (unassigned)	~30k	1 in 91	1 in 5,000
European (Finnish)	~27k	1 in 1,200	≈ 1 in 26,000
Admixed American	~22k	1 in 100	1 in 2,800
African / African American	~21k	1 in 110	≈ 1 in 6,000
East Asian	~20k	1 in 140	1 in 3,300
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 140	≈ 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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Autosomal Dominant Retinitis PigmentosaEye DiseasesEye Diseases, Hereditary

A 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 RECRUITING

NCT04123626Phase PHASE1, PHASE2ProQR TherapeuticsStarted 2019-10-07

QR-1123Sham procedure

Retinitis Pigmentosa

Promising ROd-cone DYstrophy Gene therapY

ACTIVE NOT RECRUITING

NCT05748873Phase PHASE1, PHASE2SparingVisionStarted 2023-04-12

SPVN06

Retinitis Pigmentosa

Safety and Efficacy of ZVS203e in the Treatment of Retinitis Pigmentosa Caused by RHO Gene Mutation

RECRUITING

NCT06952842Phase PHASE1, PHASE2Chigenovo Co., LtdStarted 2025-08-04