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GeneBe

RPGR

retinitis pigmentosa GTPase regulator

Basic information

Region (hg38): X:38269162-38327544

Previous symbols: [ "CRD", "RP3", "RP15", "COD1" ]

Links

ENSG00000156313NCBI:6103OMIM:312610HGNC:10295Uniprot:Q92834AlphaFoldGenCCjaxSfariGnomADPubmed

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafnessXLAllergy/Immunology/Infectious; Audiologic/OtolaryngologicAntiinfectious 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 beneficialAllergy/Immunology/Infectious; Audiologic/Otolaryngologic; Ophthalmologic1733835; 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 ClinVar and linked to the RPGR gene.

  • 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 (-)link
X-38269419-T-C Uncertain significance (Jul 27, 2022)link
X-38269432-T-C Likely benign (May 25, 2022)link
X-38269448-G-GT not provided (-)link
X-38269449-T-C Uncertain significance (Sep 16, 2021)link
X-38269453-AAATATTAGCATAAAT-A not provided (-)link
X-38269511-TATTAAGTCTTATATCTTTTAA-T not provided (-)link
X-38269549-CT-C not provided (-)link
X-38269557-CATAAGTT-C Benign (Jul 14, 2018)link
X-38269612-ACATAAATATATATTT-A not provided (-)link
X-38269629-T-C Primary ciliary dyskinesia Likely benign (Sep 15, 2021)link
X-38269632-T-A Likely benign (Jan 29, 2020)link
X-38269635-T-C Primary ciliary dyskinesia Likely benign (Dec 30, 2020)link
X-38269646-TTG-T Retinitis pigmentosa Pathogenic (Apr 01, 2018)link
X-38269667-TTG-T Retinitis pigmentosa Pathogenic (Apr 01, 2018)link
X-38269680-C-T Primary ciliary dyskinesia Likely benign (May 17, 2022)link
X-38269698-GTGGTTCTGGTCGGCATCTT-G not provided (-)link
X-38269709-C-T Primary ciliary dyskinesia Benign/Likely benign (Nov 01, 2022)link
X-38269715-CTT-C not provided (-)link
X-38269719-A-G Primary ciliary dyskinesia Likely benign (May 16, 2022)link
X-38269735-A-G Primary ciliary dyskinesia Uncertain significance (Jul 13, 2022)link
X-38269737-G-C Primary ciliary dyskinesia Uncertain significance (Aug 16, 2022)link
X-38269738-A-G Primary ciliary dyskinesia Uncertain significance (Jun 18, 2022)link
X-38269742-G-T Uncertain significance (Aug 01, 2017)link
X-38269750-A-G Primary ciliary dyskinesia Benign/Likely benign (Sep 02, 2022)link

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RPGRprotein_codingprotein_codingENST00000378505 1558402
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9980.00196123950021239520.00000807
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.252943610.8150.00002547525
Missense in Polyphen3985.2170.457661526
Synonymous-1.481531311.160.000009572034
Loss of Function4.21122.60.04420.00000159430

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00002510.0000181
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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