RHO
rhodopsin, the group of Opsin receptors
Basic information
Region (hg38): 3:129528638-129535344
Previous symbols: [ "RP4" ]
Links
Phenotypes
GenCC
Source:
- retinitis pigmentosa 4 (Definitive), mode of inheritance: Semidominant
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- congenital stationary night blindness (Supportive), mode of inheritance: AD
- congenital stationary night blindness autosomal dominant 1 (Definitive), mode of inheritance: AD
- congenital stationary night blindness autosomal dominant 1 (Strong), mode of inheritance: AD
- retinitis pigmentosa 4 (Strong), mode of inheritance: AD
- retinitis pigmentosa 4 (Strong), mode of inheritance: AR
- fundus albipunctatus (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Retinitis pigmentosa 4; Retinitis punctata albescens; Night blindness, congenital stationary, autosomal dominant 1 | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Ophthalmologic | 2613244; 2137202; 2215617; 2333895; 1882937; 1302614; 1301135; 8512476; 8358437; 7846071; 8841304; 9197578; 9888392; 10980774; 20301590; 20555336; 21174529; 22419850 |
| Oral vitamin A may slow retinal degeneration in some forms of retinitis pigmentosa |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (402 variants)
- Retinitis pigmentosa (113 variants)
- Retinitis pigmentosa 4 (106 variants)
- Congenital stationary night blindness autosomal dominant 1 (85 variants)
- Retinal dystrophy (47 variants)
- not specified (12 variants)
- Pigmentary retinal dystrophy (10 variants)
- Retinitis Pigmentosa, Dominant/Recessive (4 variants)
- Congenital Stationary Night Blindness, Dominant (4 variants)
- Retinitis pigmentosa 4, autosomal recessive (3 variants)
- Inborn genetic diseases (2 variants)
- Congenital stationary night blindness autosomal dominant 1;Retinitis pigmentosa 4 (2 variants)
- Cone dystrophy 3 (1 variants)
- Autosomal dominant retinitis pigmentosa (1 variants)
- Retinitis punctata albescens (1 variants)
- 11 conditions (1 variants)
- Congenital stationary night blindness autosomal dominant 1;Pigmentary retinal dystrophy;Retinitis pigmentosa 4 (1 variants)
- Severe early-childhood-onset retinal dystrophy (1 variants)
- Occult macular dystrophy (1 variants)
- Peripheral visual field loss;Night blindness;Blurred vision (1 variants)
- Pigmentary retinal dystrophy;Congenital stationary night blindness autosomal dominant 1;Retinitis pigmentosa 4 (1 variants)
- Autosomal recessive retinitis pigmentosa (1 variants)
- Retinal degeneration (1 variants)
- Neuropathy, congenital hypomyelinating, 2 (1 variants)
- Cone-rod dystrophy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHO gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 69 | 2 | 77 | ||
| missense | 63 | 64 | 151 | 10 | 1 | 289 |
| nonsense | 10 | 7 | 2 | 19 | ||
| start loss | 0 | |||||
| frameshift | 8 | 6 | 3 | 17 | ||
| inframe indel | 3 | 6 | 9 | |||
| splice variant | 3 | 5 | 7 | 3 | 1 | 19 |
| non coding | 3 | 24 | 2 | 29 | ||
| Total | 84 | 85 | 178 | 106 | 6 |
Highest pathogenic variant AF is 0.0000329
Variants in RHO
This is a list of pathogenic ClinVar variants found in the RHO region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-129528683-G-A | Retinitis pigmentosa • Congenital stationary night blindness autosomal dominant 1 | Benign (Jan 13, 2018) | ||
| 3-129528708-A-G | not specified • Retinitis pigmentosa • Congenital stationary night blindness autosomal dominant 1 • Retinitis pigmentosa 4 • Pigmentary retinal dystrophy | Benign (Nov 07, 2021) | ||
| 3-129528710-G-T | Congenital stationary night blindness autosomal dominant 1 • Retinitis pigmentosa | Uncertain significance (Jan 13, 2018) | ||
| 3-129528741-G-A | Uncertain significance (Oct 25, 2021) | |||
| 3-129528742-C-T | Uncertain significance (Aug 24, 2021) | |||
| 3-129528747-A-G | Uncertain significance (Sep 12, 2022) | |||
| 3-129528749-G-A | Retinal dystrophy | Uncertain significance (Dec 26, 2017) | ||
| 3-129528758-T-G | Uncertain significance (Nov 22, 2021) | |||
| 3-129528760-C-A | Uncertain significance (Aug 23, 2022) | |||
| 3-129528760-C-T | Likely benign (Oct 03, 2022) | |||
| 3-129528763-C-T | Benign (Apr 18, 2022) | |||
| 3-129528764-G-A | Retinal dystrophy | Uncertain significance (Feb 13, 2022) | ||
| 3-129528766-GC-G | Pathogenic (Aug 02, 2021) | |||
| 3-129528768-C-G | Uncertain significance (Oct 13, 2022) | |||
| 3-129528776-A-G | Uncertain significance (Apr 18, 2022) | |||
| 3-129528777-A-G | Retinitis pigmentosa 4 • Retinitis pigmentosa | Pathogenic (Oct 25, 2022) | ||
| 3-129528777-A-T | Likely pathogenic (Nov 01, 2019) | |||
| 3-129528778-T-A | Likely pathogenic (Aug 28, 2021) | |||
| 3-129528778-T-G | Retinitis pigmentosa 4 | Pathogenic/Likely pathogenic (Feb 08, 2022) | ||
| 3-129528780-C-T | Uncertain significance (Oct 28, 2022) | |||
| 3-129528781-G-A | Congenital stationary night blindness autosomal dominant 1 • Retinitis pigmentosa | Uncertain significance (Jan 13, 2018) | ||
| 3-129528783-C-A | Retinitis pigmentosa 4 | Likely pathogenic (Oct 17, 2022) | ||
| 3-129528783-C-T | Retinitis pigmentosa 4 • Retinitis pigmentosa • not specified • Retinal dystrophy | Pathogenic (Oct 18, 2022) | ||
| 3-129528784-G-A | Uncertain significance (Jan 04, 2022) | |||
| 3-129528784-G-C | Likely benign (Oct 13, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RHO | protein_coding | protein_coding | ENST00000296271 | 5 | 6530 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000131 | 0.860 | 125727 | 0 | 21 | 125748 | 0.0000835 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.242 | 209 | 219 | 0.954 | 0.0000151 | 2293 |
| Missense in Polyphen | 122 | 123.4 | 0.98864 | 1300 | ||
| Synonymous | -1.35 | 113 | 96.2 | 1.17 | 0.00000815 | 697 |
| Loss of Function | 1.35 | 8 | 13.3 | 0.600 | 5.87e-7 | 150 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000123 | 0.000123 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000141 | 0.000141 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Photoreceptor required for image-forming vision at low light intensity (PubMed:8107847, PubMed:7846071). Required for photoreceptor cell viability after birth (PubMed:2215617, PubMed:12566452). Light-induced isomerization of the chromophore 11-cis-retinal to all-trans-retinal triggers a conformational change that activates signaling via G-proteins (PubMed:8107847, PubMed:28524165, PubMed:26200343, PubMed:28753425). Subsequent receptor phosphorylation mediates displacement of the bound G- protein alpha subunit by the arrestin SAG and terminates signaling (PubMed:28524165, PubMed:26200343). {ECO:0000269|PubMed:12566452, ECO:0000269|PubMed:2215617, ECO:0000269|PubMed:26200343, ECO:0000269|PubMed:28753425, ECO:0000269|PubMed:7846071, ECO:0000269|PubMed:8107847, ECO:0000305|PubMed:28524165}.;
- Disease
- DISEASE: Retinitis pigmentosa 4 (RP4) [MIM:613731]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:12566452, ECO:0000269|PubMed:1302614, ECO:0000269|PubMed:1391967, ECO:0000269|PubMed:1833777, ECO:0000269|PubMed:1840561, ECO:0000269|PubMed:1862076, ECO:0000269|PubMed:1897520, ECO:0000269|PubMed:1985460, ECO:0000269|PubMed:19934218, ECO:0000269|PubMed:19960070, ECO:0000269|PubMed:2137202, ECO:0000269|PubMed:2215617, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:2239971, ECO:0000269|PubMed:7633434, ECO:0000269|PubMed:7981701, ECO:0000269|PubMed:7987326, ECO:0000269|PubMed:7987331, ECO:0000269|PubMed:8045708, ECO:0000269|PubMed:8076945, ECO:0000269|PubMed:8081400, ECO:0000269|PubMed:8088850, ECO:0000269|PubMed:8317502, ECO:0000269|PubMed:8353500, ECO:0000269|PubMed:8554077, ECO:0000269|PubMed:9452035}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Night blindness, congenital stationary, autosomal dominant 1 (CSNBAD1) [MIM:610445]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. {ECO:0000269|PubMed:7846071, ECO:0000269|PubMed:8107847, ECO:0000269|PubMed:8358437, ECO:0000269|PubMed:9888392}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Phototransduction - Homo sapiens (human);Integrated Breast Cancer Pathway;Integrin-mediated Cell Adhesion;Regulation of Microtubule Cytoskeleton;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;visual signal transduction;The canonical retinoid cycle in rods (twilight vision);Opsins;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Visual signal transduction: Rods;G alpha (i) signalling events;Activation of the phototransduction cascade;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR downstream signalling;VxPx cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.833
Intolerance Scores
- loftool
- 0.388
- rvis_EVS
- -0.89
- rvis_percentile_EVS
- 10.37
Haploinsufficiency Scores
- pHI
- 0.496
- hipred
- Y
- hipred_score
- 0.732
- ghis
- 0.533
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.881
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rho
- Phenotype
- immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- rho
- Affected structure
- retinal rod cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased thickness
Gene ontology
- Biological process
- retinoid metabolic process;protein phosphorylation;G protein-coupled receptor signaling pathway;visual perception;phototransduction;phototransduction, visible light;absorption of visible light;rhodopsin mediated signaling pathway;protein-chromophore linkage;regulation of rhodopsin mediated signaling pathway;photoreceptor cell maintenance;retina development in camera-type eye;cellular response to light stimulus
- Cellular component
- Golgi membrane;photoreceptor outer segment;photoreceptor inner segment;Golgi apparatus;plasma membrane;integral component of plasma membrane;cell-cell junction;integral component of membrane;Golgi-associated vesicle membrane;photoreceptor outer segment membrane;ciliary membrane;photoreceptor inner segment membrane;photoreceptor disc membrane
- Molecular function
- G protein-coupled receptor activity;11-cis retinal binding;protein binding;G protein-coupled photoreceptor activity;metal ion binding