RPGR
retinitis pigmentosa GTPase regulator
Basic information
Region (hg38): X:38269162-38327544
Previous symbols: [ "CRD", "RP3", "RP15", "COD1" ]
Links
Phenotypes
GenCC
Source:
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- primary ciliary dyskinesia (Supportive), mode of inheritance: AD
- cone-rod dystrophy (Supportive), mode of inheritance: AD
- primary ciliary dyskinesia-retinitis pigmentosa syndrome (Supportive), mode of inheritance: XL
- retinitis pigmentosa 3 (Definitive), mode of inheritance: XL
- RPGR-related retinopathy (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness | XL | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic | Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial: Individuals may demonstrate hearing loss at a relatively young age, and interventions related to recognition and management of hearing impairment may be beneficial | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Ophthalmologic | 1733835; 7611300; 8673101; 8817343; 9350809; 9399904; 9443860; 10094550; 10970770; 10932196; 12160730; 11857109; 11950860; 11875055; 14627685; 14564670; 12657579; 12920075; 15914600; 16387007; 16055928; 17480003; 21857984; 21866333; 22183348; 24043777 |
| Individuals can have hearing loss, some of which may be attributed to recurrent ear infections |
ClinVar
This is a list of variants' phenotypes submitted to
- Primary ciliary dyskinesia (718 variants)
- not provided (523 variants)
- Retinitis pigmentosa 3 (180 variants)
- Retinal dystrophy (129 variants)
- Retinitis pigmentosa (117 variants)
- not specified (49 variants)
- X-linked cone-rod dystrophy 1 (19 variants)
- X-linked cone-rod dystrophy (9 variants)
- Macular degeneration, X-linked atrophic (7 variants)
- Inborn genetic diseases (3 variants)
- Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness (3 variants)
- Retinitis pigmentosa 3;Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;X-linked cone-rod dystrophy 1;Macular degeneration, X-linked atrophic (3 variants)
- Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;Macular degeneration, X-linked atrophic;X-linked cone-rod dystrophy 1;Retinitis pigmentosa 3 (2 variants)
- Retinitis pigmentosa 3;Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;Macular degeneration, X-linked atrophic;X-linked cone-rod dystrophy 1 (2 variants)
- RETINITIS PIGMENTOSA, SINORESPIRATORY INFECTIONS, AND DEAFNESS (2 variants)
- Macular dystrophy (2 variants)
- Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;X-linked cone-rod dystrophy 1;Macular degeneration, X-linked atrophic;Retinitis pigmentosa 3 (1 variants)
- Cone dystrophy (1 variants)
- X-linked cone-rod dystrophy 1;Retinitis pigmentosa 3;Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;Macular degeneration, X-linked atrophic (1 variants)
- X-linked cone-rod dystrophy 1;Macular degeneration, X-linked atrophic;Retinitis pigmentosa 3;Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness (1 variants)
- Congenital stationary night blindness (1 variants)
- Cone dystrophy 1, X-linked (1 variants)
- Retinitis pigmentosa 6 (1 variants)
- Macular degeneration, X-linked atrophic;X-linked cone-rod dystrophy 1;Retinitis pigmentosa 3;Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness (1 variants)
- Retinitis pigmentosa 3;X-linked cone-rod dystrophy 1 (1 variants)
- Cone-rod dystrophy (1 variants)
- Pyloric stenosis;Esophageal atresia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPGR gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 110 | 12 | 124 | ||
| missense | 11 | 25 | 213 | 49 | 18 | 316 |
| nonsense | 85 | 59 | 3 | 147 | ||
| start loss | 0 | |||||
| frameshift | 112 | 88 | 63 | 32 | 4 | 299 |
| inframe indel | 60 | 33 | 1 | 94 | ||
| splice variant | 26 | 24 | 26 | 15 | 3 | 94 |
| non coding | 7 | 5 | 8 | 49 | 44 | 113 |
| Total | 301 | 234 | 316 | 255 | 81 |
Variants in RPGR
This is a list of pathogenic ClinVar variants found in the RPGR region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-38269233-T-TAAAAATTGTAAATACATCAAA | not provided (-) | |||
| X-38269419-T-C | Uncertain significance (Jul 27, 2022) | |||
| X-38269432-T-C | Likely benign (May 25, 2022) | |||
| X-38269448-G-GT | not provided (-) | |||
| X-38269449-T-C | Uncertain significance (Sep 16, 2021) | |||
| X-38269453-AAATATTAGCATAAAT-A | not provided (-) | |||
| X-38269511-TATTAAGTCTTATATCTTTTAA-T | not provided (-) | |||
| X-38269549-CT-C | not provided (-) | |||
| X-38269557-CATAAGTT-C | Benign (Jul 14, 2018) | |||
| X-38269612-ACATAAATATATATTT-A | not provided (-) | |||
| X-38269629-T-C | Primary ciliary dyskinesia | Likely benign (Sep 15, 2021) | ||
| X-38269632-T-A | Likely benign (Jan 29, 2020) | |||
| X-38269635-T-C | Primary ciliary dyskinesia | Likely benign (Dec 30, 2020) | ||
| X-38269646-TTG-T | Retinitis pigmentosa | Pathogenic (Apr 01, 2018) | ||
| X-38269667-TTG-T | Retinitis pigmentosa | Pathogenic (Apr 01, 2018) | ||
| X-38269680-C-T | Primary ciliary dyskinesia | Likely benign (May 17, 2022) | ||
| X-38269698-GTGGTTCTGGTCGGCATCTT-G | not provided (-) | |||
| X-38269709-C-T | Primary ciliary dyskinesia | Benign/Likely benign (Nov 01, 2022) | ||
| X-38269715-CTT-C | not provided (-) | |||
| X-38269719-A-G | Primary ciliary dyskinesia | Likely benign (May 16, 2022) | ||
| X-38269735-A-G | Primary ciliary dyskinesia | Uncertain significance (Jul 13, 2022) | ||
| X-38269737-G-C | Primary ciliary dyskinesia | Uncertain significance (Aug 16, 2022) | ||
| X-38269738-A-G | Primary ciliary dyskinesia | Uncertain significance (Jun 18, 2022) | ||
| X-38269742-G-T | Uncertain significance (Aug 01, 2017) | |||
| X-38269750-A-G | Primary ciliary dyskinesia | Benign/Likely benign (Sep 02, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RPGR | protein_coding | protein_coding | ENST00000378505 | 15 | 58402 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00196 | 123950 | 0 | 2 | 123952 | 0.00000807 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 294 | 361 | 0.815 | 0.0000254 | 7525 |
| Missense in Polyphen | 39 | 85.217 | 0.45766 | 1526 | ||
| Synonymous | -1.48 | 153 | 131 | 1.16 | 0.00000957 | 2034 |
| Loss of Function | 4.21 | 1 | 22.6 | 0.0442 | 0.00000159 | 430 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000251 | 0.0000181 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Could be a guanine-nucleotide releasing factor. Plays a role in ciliogenesis. Probably regulates cilia formation by regulating actin stress filaments and cell contractility. Plays an important role in photoreceptor integrity. May play a critical role in spermatogenesis and in intraflagellar transport processes (By similarity). May be involved in microtubule organization and regulation of transport in primary cilia. {ECO:0000250, ECO:0000269|PubMed:21933838}.;
- Disease
- DISEASE: Retinitis pigmentosa 3 (RP3) [MIM:300029]: A X-linked 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. In RP3, affected males have a severe phenotype, and carrier females show a wide spectrum of clinical features ranging from completely asymptomatic to severe retinitis pigmentosa. Heterozygous women can manifest a form of choroidoretinal degeneration which is distinguished from other types by the absence of visual defects in the presence of a brilliant, scintillating, golden-hued, patchy appearance most striking around the macula, called a tapetal-like retinal reflex. {ECO:0000269|PubMed:10482958, ECO:0000269|PubMed:10737996, ECO:0000269|PubMed:10932196, ECO:0000269|PubMed:10937588, ECO:0000269|PubMed:10970770, ECO:0000269|PubMed:11180598, ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:12657579, ECO:0000269|PubMed:14564670, ECO:0000269|PubMed:24981858, ECO:0000269|PubMed:8673101, ECO:0000269|PubMed:8817343, ECO:0000269|PubMed:9399904, ECO:0000269|PubMed:9855162}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa and sinorespiratory infections with or without deafness (RPDSI) [MIM:300455]: A disease characterized by the association primary ciliary dyskinesia features with retinitis pigmentosa. Some patients also manifest deafness. {ECO:0000269|PubMed:12920075, ECO:0000269|PubMed:14627685}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cone-rod dystrophy, X-linked 1 (CORDX1) [MIM:304020]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa. In cone-rod dystrophy X-linked type 1 the degree of rod-photoreceptor involvement can be variable, with degeneration increasing as the disease progresses. Affected individuals (essentially all of whom are males) present with decreased visual acuity, myopia, photophobia, abnormal color vision, full peripheral visual fields, decreased photopic electroretinographic responses, and granularity of the macular retinal pigment epithelium. Although penetrance appears to be nearly 100%, there is variable expressivity with respect to age at onset and severity of symptoms. {ECO:0000269|PubMed:11857109}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Macular degeneration, X-linked, atrophic (MDXLA) [MIM:300834]: An ocular disorder characterized by macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. Some patients manifest extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) show normal cone and rod responses in some affected males despite advanced macular degeneration. {ECO:0000269|PubMed:12160730}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- loftool
- 0.101
- rvis_EVS
- 2.8
- rvis_percentile_EVS
- 99.04
Haploinsufficiency Scores
- pHI
- 0.542
- hipred
- N
- hipred_score
- 0.481
- ghis
- 0.415
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.384
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rpgr
- Phenotype
- 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); 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); muscle phenotype;
Zebrafish Information Network
- Gene name
- rpgrb
- Affected structure
- retinal rod cell
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- intracellular protein transport;visual perception;intraciliary transport;response to stimulus;cilium assembly
- Cellular component
- photoreceptor outer segment;Golgi apparatus;centrosome;ciliary basal body;sperm flagellum
- Molecular function
- RNA binding;guanyl-nucleotide exchange factor activity;protein binding