Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

RPGR

contributors: npt/pgu/shn - updated : 13-03-2012

HGNC name	retinitis pigmentosa GTPase regulator
HGNC id	10295

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CORDX1 cone-rod dystrophy 1 ICS9 immotile cilia syndrome 9 MDXA1 atrophic macular degeneration 1 RP15 retinitis pigmentosa 15 RP3 retinitis pigmentosa 3
Location	Xp11.4      Physical location : 38.128.423 - 38.186.788
Synonym name	retinitis pigmentosa 3 GTPase regulator
	retinitis pigmentosa 15
	cone dystrophy 1 (X-linked)
Synonym symbol(s)	CRD, COD1, PCDX, XLRP3, orf15, CORDX1

DNA

TYPE	functioning gene
STRUCTURE	58.37 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure	RPGR transcript undergoes complex alternative splicing to express both constitutive (Rpgr(ex1-19)) and Rpgr(ORF15) variants
	five additional exons, preferentially expressed in retina, were found: 15b1, 15b2, 15a, ORF14, and ORF15. ORF15 is a large 3-prime terminal exon consisting of exon 15 and extending into part of intron 15
	the exon ORF15 protein domain contains an unusual region of low sequence complexity with high glutamic acid and glycine content
	by RT-PCR analysis of human retina cDNA, a novel exon in intron 9 has been identified and was designated exon 9A, of the RPGR gene

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - DXS1049 - DXS8090 - RPGR - DXS1069 - DXS1068 - cen

RNA

TRANSCRIPTS	type	messenger

text

a new exon, designated exon 15A (ORF15) is expressed exclusively in human retina. Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported. The new exon 9A variant is predominantly expressed in the inner segment of human cones with a weaker signal in rods

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001034853 15 - 4.718 NP_001030025 - 1152 Outer segment of cone and rod photoreceptors. RPGR is expressed in connecting cilia of rods and cones. In the epithelial lining of human bronchial and sinus tissues, in human fetal cochlea, including the stria vascularis, the suprastrial cells, and the apical portion of the spiral limbus. 2003 14627685 retinitis pigmentosa GTPase regulator isoform C contains an unusual purine-rich C-terminal exon ORF15 NM_000328 19 - 3.082 NP_000319 90 815 Outer segment of photoreceptors. RPGR is expressed in connecting cilia of rods and cones. In the epithelial lining of human bronchial and sinus tissues, in human fetal cochlea, including the stria vascularis, the suprastrial cells, and the apical portion of the spiral limbus. 2000 10725384 retinitis pigmentosa GTPase regulator isoform

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive liver       moderately Endocrine pancreas       highly Nervous brain       highly Reproductive female system placenta     highly   male system testis     highly Respiratory lung       moderately Urinary kidney       moderately Visual eye retina     specific

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Visual rod photoreceptor

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	retinal pigment epithelium, placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal half (six) seven internal repeats (in a structure highly similar to the guanine nucleotide exchange factor (GEF) of the Ras-like GTPase Ran) and regulator of chromosome condensation, RCC1 domain
	RHD domain interacting with the delta subunit of rod cGMP phosphodiesterase (PDE6D)
	a highly repetitive, purine-rich internal region
	at the C terminus an isoprenylation site

HOMOLOGY

interspecies	ortholog to Rpgr, Mus musculus
	homolog to LOC793925, Danio rerio
	ortholog to Rpgr, Rattus norvegicus
	ortholog to RPGR, Pan troglodytes

Homologene

FAMILY

CATEGORY

structural protein , transport

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	connective cilia of cone and rod outer segment photoreceptors
	ORF15 localizing in centrosome and spindle poles
	primarily localizes to the sensory cilium of photoreceptors

basic FUNCTION	retinitis pigmentosa GTPase regulator, potentially involved in vesicle transport
	putative maintenance of polarized distribution of outer segment-specific protein(s)
	microtubule organization and regulation of transport in primary cilia
	RPGR is essential for the maintenance of photoreceptor cells viability
	RPGR plays a role in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution
	predominantly a cilia-centrosomal protein that interacts with many ciliary proteins
	involved in the maintenance of the cilium and not ciliogenesis
	functions as a GEF (guanine nucleotide exchange factor) for RAB8A and RPGR
	RAB8A association may facilitate ciliary trafficking
	may play a critical role in promoting RAB8A function in photoreceptors
	novel function for RPGR in cilia formation and in the regulation of actin stress filaments

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

text	intracellular protein traffic along the connecting cilia of the photoreceptor cells

PATHWAY

metabolism

signaling

sensory transduction/vision

a component

INTERACTION

DNA

RNA

small molecule

protein	delta subunit of rod cyclic GMP phosphodiesterase, PDEdelta
	RPGR-interacting protein 1, RPGRIP1
	structural maintenance of chromosomes 1A, SMC1A and structural maintenance of chromosomes 3, SMC3
	C2 domain of RPGR-ORF15 interacts with the shuttling protein nucleophosmin (NPM1)
	interact (directly or indirectly) with several ciliary proteins, including RPGRIP1-like (RPGRIP1L/NPHP8) and CEP290/NPHP6
	NPHP4 interacts with RPGR (RCC1-like domain of RPGR interacts with the N-terminal 316 AAs of NPHP4)
	interacts with the small GTPase RAB8A, which participates in cilia biogenesis and maintenance (modulates intracellular localization and function of RAB8A)
	may associate with a variety of other transport and scaffold proteins en route to the cilium, and a major function within the photoreceptor cilium is nascent disc formation, by regulating actin-mediated membrane extension

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

RP3 , RP15 , CORDX1 , MDXA1 , ICS9

related resource

Retinal Information Network

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurosensorial     RPGR-ORF15 variant reconstitutes RPGR function, possible gene replacement therapy for RPGR-null mutations respiratory lung   future therapeutic strategies can be appropriately designed to target a future therapeutic strategies can be appropriately designed to target a complete or partial loss of function of the mutant RPGR protein in patients with ciliary disorders

ANIMAL & CELL MODELS

	RPGR-deficient murine display ectopic localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin leading to both cone and rod photoreceptors degeneration
	canine model of early onset X-linked retinitis pigmentosa (XLRP) caused by a two-nucleotide microdeletion in RPGR ORF15 have abnormal development of photoreceptors followed by progressive rod-cone degeneration and early inner retina remodeling
	canine model of XLRP caused by an RPGR exon ORF15 microdeletion display dwonregulation of PAX6, CHML, RDH11, CRX, SAG, CAMK2G, NTRK2, PRKCB, RALA, RBBP6, RNF41, SMYD3, SPP1, TUBB2C, SLC25A5, NKAP, ELOVL6, GLOD4, NDUFS4, REEP1 and TARS2 genes
	overexpression of the Rpgr(ex1-19) variant resulted in atypical accumulation of Rpgr in photoreceptor outer segments, abnormal photoreceptor morphology, and severe retinal degeneration (