RP1

Summary

RP1 (RP1 axonemal microtubule associated, HGNC:10263) is a protein-coding gene on chromosome 8q11.23-q12.1, encoding Oxygen-regulated protein 1 (P56715). Microtubule-associated protein regulating the stability and length of the microtubule-based axoneme of photoreceptors.

This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains, which bind microtubules and regulate microtubule polymerization. The encoded protein is a photoreceptor microtubule-associated protein and is required for correct stacking of outer segment disc. This protein and the RP1L1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Because of its response to in vivo retinal oxygen levels, this protein was initially named ORP1 (oxygen-regulated protein-1). This protein was subsequently designated RP1 (retinitis pigmentosa 1) when it was found that mutations in this gene cause autosomal dominant retinitis pigmentosa. Mutations in this gene also cause autosomal recessive retinitis pigmentosa. Transcript variants resulted from an alternative promoter and alternative splicings have been found, which overlap the current reference sequence and has several exons upstream and downstream of the current reference sequence. However, the biological validity and full-length nature of some variants cannot be determined at this time.

Source: NCBI Gene 6101 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RP1-related dominant retinopathy (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 1,585 total — 203 pathogenic, 60 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• MANE Select transcript: NM_006269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10263
Approved symbol	RP1
Name	RP1 axonemal microtubule associated
Location	8q11.23-q12.1
Locus type	gene with protein product
Status	Approved
Aliases	DCDC4A, ORP1
Ensembl gene	ENSG00000104237
Ensembl biotype	protein_coding
OMIM	603937
Entrez	6101

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000220676, ENST00000518787, ENST00000522001, ENST00000602362, ENST00000636932, ENST00000637698, ENST00000646684, ENST00000650534

RefSeq mRNA: 2 — MANE Select: NM_006269 NM_001375654, NM_006269

CCDS: CCDS6160

Canonical transcript exons

ENST00000220676 — 4 exons

Exon	Start	End
ENSE00000693896	54622117	54622288
ENSE00000819425	54624670	54630834
ENSE00001191956	54620955	54621581
ENSE00003892992	54616096	54616202

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 92.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9301 / max 370.7442, expressed in 164 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88879	0.2980	33
88884	0.2616	11
88876	0.1420	61
88875	0.0759	32
88877	0.0333	12
88881	0.0299	11
88880	0.0183	5
88882	0.0151	7
88885	0.0130	3
88878	0.0125	7

Top tissues by expression

217 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.73	gold quality
right lung	UBERON:0002167	72.47	gold quality
bronchial epithelial cell	CL:0002328	71.14	gold quality
bronchus	UBERON:0002185	69.76	gold quality
nasal cavity mucosa	UBERON:0001826	61.84	gold quality
fallopian tube	UBERON:0003889	60.52	gold quality
upper lobe of left lung	UBERON:0008952	59.14	gold quality
metanephros cortex	UBERON:0010533	59.06	gold quality
upper lobe of lung	UBERON:0008948	58.46	gold quality
lung	UBERON:0002048	57.76	gold quality
adult mammalian kidney	UBERON:0000082	56.66	gold quality
retina	UBERON:0000966	55.71	gold quality
pigmented layer of retina	UBERON:0001782	55.71	gold quality
testis	UBERON:0000473	54.95	gold quality
right testis	UBERON:0004534	54.13	gold quality
left testis	UBERON:0004533	53.92	gold quality
metanephros	UBERON:0000081	53.50	gold quality
kidney	UBERON:0002113	52.13	gold quality
body of stomach	UBERON:0001161	51.71	gold quality
left uterine tube	UBERON:0001303	51.56	gold quality
stomach	UBERON:0000945	51.52	gold quality
cortex of kidney	UBERON:0001225	51.29	gold quality
spleen	UBERON:0002106	51.16	gold quality
endometrium	UBERON:0001295	49.54	gold quality
endocervix	UBERON:0000458	48.70	gold quality
right ovary	UBERON:0002118	47.69	gold quality
sural nerve	UBERON:0015488	47.20	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	3574.43
E-GEOD-137537	yes	2430.63
E-MTAB-11121	yes	1870.86
E-CURD-119	yes	1807.37
E-GEOD-131882	yes	1768.21
E-HCAD-15	yes	1545.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting RP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-6853-3P	99.36	70.79	1558

Literature-anchored findings (GeneRIF, showing 40)

• The presence of RP1/Rp1 in connecting cilia suggests that it may participate in transport of proteins or maintenance of cilial structure. (PMID:11773008)
• Study data suggest that genetic variation at the RP1 locus is one of the likely candidate determinants for plasma triglyceride and HDL-cholesterol metabolisms. (PMID:12764676)
• RP1 (Arg677ter) mutation in a patient with retinitis pigmentosa suggests that this common autosomal dominant RP mutation can arise independently in the population (PMID:12882812)
• The most common Arg677X mutation in the white population was not found in the Japanese population; instead a novel mutation was found. (PMID:15183808)
• Autosomal recessive retinitis pigmentosa is associated with homozygous mutations of the RP1 gene. (PMID:15863674)
• These results provide strong evidence that mutations in RP1 can result in recessive as well as dominant retinitis pigmentosa. (PMID:15980210)
• Mutations were only found in Caucasian families with origins in the British Isles. RP1 mutation frequency of 5.3% in South African autosomal dominant retinitis pigmentosa is comparable to frequency reported in other populations. (PMID:16568030)
• N985Y mutation segregated with the phenotype from 1 Chinese family with mild and late-onset autosomal dominant retinitis pigmentosa (ADRP) a finding that has not been documented in other races. (PMID:18347624)
• RHO, PRPF31, RP1, and IMPDH1 were screened and causative mutations were identifiedin 4% of isolated and 2% of autosomal dominant forms of retinitis pigmentosa patients from India. (PMID:18552984)
• This report is the first to associate autosomal recessive retinitis pigmentosa with compound heterozygous nonsense mutations in RP1. (PMID:19933189)
• A relatively higher frequency of missense mutations found in the Chinese patients may suggest an ethnic diversity in the RP1 mutation patterns. (PMID:20664799)
• We describe the clinical findings in the first case, to our knowledge, of unilateral retinitis pigmentosa in a person carrying a germline mutation in RP1 gene. Detailed evaluation confirmed the dysfunction to be confined to one eye. (PMID:21746989)
• Four novel deletions and nonsense mutations in the RP1, of which two may represent recurrent mutations in this population, have been identified in a French cohort of retinitis pigmentosa. (PMID:22052604)
• The distribution of these novel and previously reported RP1 mutations makes it challenging to describe a unifying mutational mechanism for dominant versus recessive RP1-related retinitis pigmentosa. (PMID:22317909)
• p.Ser542Stop is a single founder mutation and the most prevalent described mutation in the Spanish population. It causes early-onset RP with a rapid macular degeneration and is responsible for 4.5% of all cases. (PMID:22917891)
• molecular mechanism of RP1 mutation (PMID:22927954)
• The most severe missense mutation occurred in patients with p.D984G in RP1. (PMID:23049240)
• A novel homozygous retinitis pigmentosa nonsense mutation in exon 4 of the RP1 gene, c.1012C>T (p.R338*) was identified in the proband and her two affected sisters. (PMID:23077400)
• RP1 phosphorylation at Ser(236) by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association. (PMID:23844040)
• Data found pathogenic DNA variants in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases. (PMID:23940504)
• The L66P mutation in the first doublecortin domain of the Rp1 gene impairs Rp1 protein localization and function, leading to abnormalities in photoreceptor outer segment structure and progressive photoreceptor degeneration. (PMID:25088982)
• Two novel heterozygous null mutations in RP1 co-segregate with the disease in autosomal recessive retinitis pigmentosa patients. (PMID:25494902)
• it reports that different regions of RP1 can also lead to arRCD. (PMID:25692139)
• We suggest that arRP patients with high myopic refractive error should be preferentially analysed for RP1 mutations. (PMID:25883087)
• seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis (PMID:26806561)
• These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families. (PMID:27307693)
• Three XLRP families (RP-001, RP-002, and RP-003) were reported in this study, and 2 different disease-causing mutations were detected. We found 3 genetic variants: a novel mutation c.1591G>T in exon 14 and a novel polymorphism c.1105C>T in exon 10, resulting in p.Glu531* and p.Arg369Cys of RPGR gene, respectively, and one already known mutation c.413A>G in exon 2, resulting in a p.Glu138Gly of RP2 gene. (PMID:27768226)
• This study expands the mutational spectrums of RP1 for retinitis pigmentosa. (PMID:29425069)
• This is the first description of a Japanese patient with autosomal recessive retinitis pigmentosa (arRP) caused by RP1 mutations. Additional data are necessary to more accurately determine the clinical course and mutation spectrum in patients with RP1-related arRP. (PMID:30027431)
• Since mutations at various points along exon 4 have divergent consequences, genetic testing alone may be insufficient for counseling, but recessive inheritance should be considered likely in severe early-onset cases. (PMID:30731082)
• Mutations in the RP1 gene are associated with a broad spectrum of progressive retinal dystrophies. In addition to autosomal dominant RP and autosomal recessive retinitis pigmentosa, our study provides further evidence that autosomal recessive cone-rod dystrophy and autosomal recessive macular dystrophy are RP1-associated phenotypes as well. (PMID:30913292)
• These results suggest that rare conditions can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance. (PMID:31253780)
• Homozygous loss-of-function mutations in RP1 gene is associated with retinitis pigmentosa. (PMID:31833436)
• Retinitis Pigmentosa Due to Rp1 Biallelic Variants. (PMID:32005865)
• A founder Alu insertion in RP1 gene in Japanese patients with retinitis pigmentosa. (PMID:32193659)
• Clinical heterogeneity in retinitis pigmentosa caused by variants in RP1 and RLBP1 in five extended consanguineous pedigrees. (PMID:32587456)
• Clinical characteristics and high resolution retinal imaging of retinitis pigmentosa caused by RP1 gene variants. (PMID:32627106)
• In Silico identification of a common mobile element insertion in exon 4 of RP1. (PMID:34183725)
• Identification of RP1 as the genetic cause of retinitis pigmentosa in a multi-generational pedigree using Extremely Low-Coverage Whole Genome Sequencing (XLC-WGS). (PMID:36341727)
• LncRNA RP1-276N6.2 Expression and RP1-276N6.2 Gene Polymorphisms Contribute to the Risk of Coronary Artery Disease in Chinese Han Population. (PMID:37843894)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rp1	ENSDARG00000077687
mus_musculus	Rp1	ENSMUSG00000025900
rattus_norvegicus	Rp1	ENSRNOG00000008807
caenorhabditis_elegans	F27C1.11	WBGENE00017858
caenorhabditis_elegans	F27C1.13	WBGENE00017860

Paralogs (1): RP1L1 (ENSG00000183638)

Protein

Protein identifiers

Oxygen-regulated protein 1 — P56715 (reviewed: P56715)

Alternative names: Retinitis pigmentosa 1 protein, Retinitis pigmentosa RP1 protein

All UniProt accessions (3): A0A1B0GTV9, A0A1B0GUH0, P56715

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-associated protein regulating the stability and length of the microtubule-based axoneme of photoreceptors. Required for the differentiation of photoreceptor cells, it plays a role in the organization of the outer segment of rod and cone photoreceptors ensuring the correct orientation and higher-order stacking of outer segment disks along the photoreceptor axoneme.

Subunit / interactions. Interacts (via the doublecortin domains) with microtubules. Interacts with RP1L1. Interacts with MAK.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cell projection. Cilium. Photoreceptor outer segment.

Tissue specificity. Expressed in retina. Not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, spleen and pancreas.

Disease relevance. Retinitis pigmentosa 1 (RP1) [MIM:180100] 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The doublecortin domains, which mediate interaction with microtubules, are required for regulation of microtubule polymerization and function in photoreceptor differentiation.

RefSeq proteins (2): NP_001362583, NP_006260* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003533	Doublecortin_dom	Domain
IPR036572	Doublecortin_dom_sf	Homologous_superfamily

Pfam: PF03607

UniProt features (42 total): sequence variant 33, region of interest 5, domain 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56715-F1	37.45	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): HARRIS_HYPOXIA, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, GOBP_NEUROGENESIS, FOXO4_01, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS

GO Biological Process (15): visual perception (GO:0007601), phototransduction, visible light (GO:0007603), axoneme assembly (GO:0035082), intracellular signal transduction (GO:0035556), photoreceptor cell outer segment organization (GO:0035845), photoreceptor cell development (GO:0042461), photoreceptor cell maintenance (GO:0045494), retinal rod cell development (GO:0046548), retinal cone cell development (GO:0046549), retina development in camera-type eye (GO:0060041), cellular response to light stimulus (GO:0071482), positive regulation of non-motile cilium assembly (GO:1902857), response to light stimulus (GO:0009416), cell projection organization (GO:0030030), retina morphogenesis in camera-type eye (GO:0060042)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (12): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), microtubule (GO:0005874), microtubule associated complex (GO:0005875), axoneme (GO:0005930), photoreceptor connecting cilium (GO:0032391), ciliary tip (GO:0097542), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995), photoreceptor cell cilium (GO:0097733)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular anatomical structure	2
cellular component organization	2
eye photoreceptor cell development	2
photoreceptor cell cilium	2
microtubule cytoskeleton	2
sensory perception of light stimulus	1
phototransduction	1
detection of visible light	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
signal transduction	1
photoreceptor cell development	1
photoreceptor cell differentiation	1
neuron development	1
retina homeostasis	1
multicellular organismal process	1
retinal rod cell differentiation	1
retinal cone cell differentiation	1
camera-type eye development	1
anatomical structure development	1
response to light stimulus	1
cellular response to radiation	1
positive regulation of cilium assembly	1
regulation of non-motile cilium assembly	1
non-motile cilium assembly	1
response to radiation	1
anatomical structure morphogenesis	1
camera-type eye morphogenesis	1
retina development in camera-type eye	1
tubulin binding	1
binding	1
polymeric cytoskeletal fiber	1
protein-containing complex	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
ciliary transition zone	1
cilium	1

Protein interactions and networks

STRING

781 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RP1	NRL	P54845	447
RP1	CRX	O43186	438
RP1	MATCAP2	Q8NCT3	370
RP1	PDE6B	P35913	359
RP1	ACTB	P02570	299
RP1	DCX	O43602	288
RP1	AKAP19	P0C876	257
RP1	BRINP2	Q9C0B6	256
RP1	TRAM1	Q15629	247
RP1	SPHKAP	Q2M3C7	246
RP1	GALNT7	Q86SF2	240
RP1	GPR63	Q9BZJ6	236
RP1	GPRIN3	Q6ZVF9	232
RP1	NUDT7	P0C024	229
RP1	XKR4	Q5GH76	229

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RP1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
RP1	NPM1	psi-mi:“MI:0915”(physical association)	0.400
RP1	BCLAF1	psi-mi:“MI:0915”(physical association)	0.400
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): RP1 (Affinity Capture-MS), RP1 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), BCLAF1 (Proximity Label-MS), RP1 (Affinity Capture-MS), RP1 (Affinity Capture-MS), RP1 (Cross-Linking-MS (XL-MS)), RP1 (Cross-Linking-MS (XL-MS)), RP1 (Affinity Capture-MS), RP1 (Affinity Capture-MS), RP1 (Proximity Label-MS)

ESM2 similar proteins: A1L2H3, A2AKX3, A5D8S0, B0S6S9, D3Z987, E1BC15, O43303, O60673, O95405, P56715, Q03188, Q2M2Z5, Q3MHH3, Q3V089, Q569L8, Q5BQN8, Q5CZC0, Q5DTT3, Q5R9I1, Q5VWN6, Q61493, Q641I1, Q6NS59, Q6NSW3, Q6ZP01, Q6ZU52, Q7TSH4, Q7Z333, Q7Z3T8, Q80U44, Q80U59, Q86UW6, Q86WS4, Q86XD8, Q8IXS0, Q8MJ03, Q8MJ04, Q8MJ06, Q8N1H7, Q8N7Z5

Diamond homologs: A2VCK2, A8MYV0, D3ZR10, P56715, P56716, Q550F6, Q5DU00, Q69Z08, Q8CGM2, Q8IWN7, Q8MJ03, Q8MJ04, Q8MJ05, Q8MJ06, Q9D1B8, Q9UHG0, D2I3C6, O15075, O43602, O88809, Q5MPA9, Q6PGN3, Q8N568, Q95QC4, Q9JLM8, B3NKK1, B4GXC2, B4IMC3, B4IT27, B4NSS9, B5DK35, Q7PLI7, Q8BWQ5, Q9ESI7, Q9VUI3, C0H4E4, O00423, O95834, Q05BC3, Q26613

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1585 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	203
Likely pathogenic	60
Uncertain significance	917
Likely benign	262
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069795	NM_006269.2(RP1):c.312_315del (p.Leu105fs)	Pathogenic
1070812	NM_006269.2(RP1):c.2352_2356del (p.Ile785fs)	Pathogenic
1071082	NM_006269.2(RP1):c.284dup (p.Glu96fs)	Pathogenic
1071351	NM_006269.2(RP1):c.2334del (p.Lys778fs)	Pathogenic
1073337	NM_006269.2(RP1):c.696T>G (p.Tyr232Ter)	Pathogenic
1074882	NM_006269.2(RP1):c.2105_2106insG (p.Ile702fs)	Pathogenic
1075497	NM_006269.2(RP1):c.3639_3652del (p.Thr1214fs)	Pathogenic
1075672	NM_006269.2(RP1):c.6154C>T (p.Gln2052Ter)	Pathogenic
1076686	NM_006269.2(RP1):c.513del (p.Leu171_Leu172insTer)	Pathogenic
1076794	NM_006269.2(RP1):c.2018del (p.Lys673fs)	Pathogenic
1213898	NM_006269.2(RP1):c.532C>T (p.Gln178Ter)	Pathogenic
1213902	NM_006269.2(RP1):c.2079del (p.Gly694fs)	Pathogenic
1284630	NM_006269.2(RP1):c.2732C>G (p.Ser911Ter)	Pathogenic
1323531	NM_006269.2(RP1):c.257dup (p.Arg87fs)	Pathogenic
1325011	NM_006269.2(RP1):c.1986del (p.Lys663fs)	Pathogenic
1358118	NM_006269.2(RP1):c.3728_3729del (p.Glu1243fs)	Pathogenic
1358934	NM_006269.2(RP1):c.1444C>T (p.Gln482Ter)	Pathogenic
1375325	NM_006269.2(RP1):c.2607del (p.Lys871fs)	Pathogenic
1385798	NM_006269.2(RP1):c.2072del (p.Ala691fs)	Pathogenic
1401598	NM_006269.2(RP1):c.150_168delinsAGACCCCCAATT (p.Val51fs)	Pathogenic
1406268	NM_006269.2(RP1):c.2321T>G (p.Leu774Ter)	Pathogenic
1410895	NM_006269.2(RP1):c.4587_4590del (p.Ser1529fs)	Pathogenic
1424798	NM_006269.2(RP1):c.72del (p.Arg25fs)	Pathogenic
1426124	NM_006269.2(RP1):c.2323del (p.Thr775fs)	Pathogenic
1428425	NM_006269.2(RP1):c.2747_2763del (p.Ile916fs)	Pathogenic
1430123	NM_006269.2(RP1):c.491del (p.Pro164fs)	Pathogenic
143137	NM_006269.2(RP1):c.650del (p.Gly217fs)	Pathogenic
1436096	NM_006269.2(RP1):c.1720_1721del (p.Ser574fs)	Pathogenic
1437029	NM_006269.2(RP1):c.2017A>T (p.Lys673Ter)	Pathogenic
1437481	NM_006269.2(RP1):c.2215G>T (p.Glu739Ter)	Pathogenic

SpliceAI

804 predictions. Top by Δscore:

Variant	Effect	Δscore
8:54619157:GGCT:G	donor_gain	1.0000
8:54619158:GCT:G	donor_gain	1.0000
8:54619160:T:G	donor_gain	1.0000
8:54619160:T:TG	donor_gain	1.0000
8:54618259:GGC:G	donor_gain	0.9900
8:54620950:TCTA:T	acceptor_loss	0.9900
8:54620951:CTA:C	acceptor_loss	0.9900
8:54620952:TA:T	acceptor_loss	0.9900
8:54620953:A:AG	acceptor_gain	0.9900
8:54620954:G:GG	acceptor_gain	0.9900
8:54621557:GCT:G	donor_gain	0.9900
8:54621574:G:GT	donor_gain	0.9900
8:54621577:GGAGG:G	donor_gain	0.9900
8:54621578:GAGGG:G	donor_gain	0.9900
8:54621579:A:T	donor_gain	0.9900
8:54621580:GG:G	donor_gain	0.9900
8:54621581:GG:G	donor_gain	0.9900
8:54622287:GA:G	donor_gain	0.9900
8:54622289:G:GG	donor_gain	0.9900
8:54620952:TAGG:T	acceptor_gain	0.9800
8:54621553:TC:T	donor_gain	0.9800
8:54621578:GAGG:G	donor_gain	0.9800
8:54616200:GTG:G	donor_gain	0.9700
8:54616203:G:GG	donor_gain	0.9700
8:54620951:CTAGG:C	acceptor_gain	0.9700
8:54621579:AGGG:A	donor_loss	0.9700
8:54621583:TGAGC:T	donor_loss	0.9700
8:54621584:G:GG	donor_loss	0.9700
8:54621585:A:AC	donor_loss	0.9700
8:54624584:T:A	acceptor_gain	0.9700

AlphaMissense

14424 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:54621084:T:C	F40L	0.997
8:54621085:T:C	F40S	0.997
8:54621086:C:A	F40L	0.997
8:54621086:C:G	F40L	0.997
8:54621092:G:C	K42N	0.997
8:54621092:G:T	K42N	0.997
8:54621108:T:C	F48L	0.997
8:54621110:C:A	F48L	0.997
8:54621110:C:G	F48L	0.997
8:54621175:T:C	L70S	0.995
8:54621198:T:C	F78L	0.995
8:54621200:T:A	F78L	0.995
8:54621200:T:G	F78L	0.995
8:54621284:T:G	C106W	0.995
8:54621090:A:G	K42E	0.994
8:54621214:T:A	I83N	0.994
8:54621276:T:G	Y104D	0.993
8:54621282:T:C	C106R	0.993
8:54622180:T:C	F227L	0.993
8:54622182:T:A	F227L	0.993
8:54622182:T:G	F227L	0.993
8:54621087:T:G	Y41D	0.992
8:54621209:G:C	R81S	0.992
8:54621209:G:T	R81S	0.992
8:54621259:T:C	L98P	0.992
8:54621100:A:G	D45G	0.991
8:54621144:T:C	F60L	0.991
8:54621146:T:A	F60L	0.991
8:54621146:T:G	F60L	0.991
8:54621214:T:G	I83S	0.991

dbSNP variants (sampled 300 via entrez): RS1000006861 (8:54789626 A>C,G), RS1000021854 (8:54701897 A>G), RS1000034454 (8:54697349 G>A), RS1000034715 (8:54740152 T>C), RS1000035548 (8:54847862 C>T), RS1000036082 (8:54782151 T>C), RS1000036736 (8:54750032 G>A), RS1000051755 (8:54613400 A>G,T), RS1000055338 (8:54818744 G>A), RS1000062149 (8:54675563 C>A), RS1000065518 (8:54567833 G>A), RS1000066443 (8:54654579 A>C,G), RS1000073643 (8:54658646 G>T), RS1000080968 (8:54567997 G>A), RS1000084927 (8:54685089 T>C)

Disease associations

OMIM: gene MIM:603937 | disease phenotypes: MIM:180100, MIM:268000, MIM:204000, MIM:145750, MIM:120970, MIM:535000

GenCC curated gene-disease

Disease	Classification	Inheritance
RP1-related recessive retinopathy	Definitive	Autosomal recessive
RP1-related dominant retinopathy	Definitive	Semidominant
retinitis pigmentosa 1	Definitive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
RP1-related dominant retinopathy	Definitive	SD
RP1-related recessive retinopathy	Definitive	AR

Mondo (10): retinitis pigmentosa 1 (MONDO:0008377), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), RP1-related recessive retinopathy (MONDO:0800399), retinal disorder (MONDO:0005283), Leber congenital amaurosis 1 (MONDO:0008764), hypertriglyceridemia 1 (MONDO:0007788), cone-rod dystrophy (MONDO:0015993), Leber hereditary optic neuropathy (MONDO:0010788), RP1-related dominant retinopathy (MONDO:0800400)

Orphanet (5): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65), Cone rod dystrophy (Orphanet:1872), Leber hereditary optic neuropathy (Orphanet:104)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000575	Scotoma
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0003621	Juvenile onset
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007688	Undetectable light- and dark-adapted electroretinogram
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract

GWAS associations

0 associations (top):

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D029242	Optic Atrophy, Hereditary, Leber	C10.292.700.225.500.400; C10.574.500.662.400; C11.270.564.400; C11.640.451.451.400; C16.320.290.564.400; C16.320.400.630.400; C18.452.660.670
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C538365	Retinitis pigmentosa 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066318 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Tobacco Smoke Pollution	affects expression	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases ubiquitination	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5550809	Binding	Binding affinity to ORP1 (unknown origin)	Fluorescent probes and degraders of the sterol transport protein Aster-A. — Bioorg Med Chem

Cellosaurus cell lines

60 cell lines: 56 transformed cell line, 3 induced pluripotent stem cell, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AL19	GM08947	Transformed cell line	Male
CVCL_AL25	GM08953	Transformed cell line	Male
CVCL_AL28	GM08956	Transformed cell line	Female
CVCL_AL30	GM08958	Transformed cell line	Female
CVCL_AL32	GM08960	Transformed cell line	Male
CVCL_AL34	GM08962	Transformed cell line	Male
CVCL_AL37	GM08965	Transformed cell line	Male
CVCL_AL41	GM08969	Transformed cell line	Male
CVCL_AL43	GM08971	Transformed cell line	Male
CVCL_AL48	GM08978	Transformed cell line	Female

Clinical trials (associated diseases)

237 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01014052	PHASE1	COMPLETED	Safety/Proof of Concept Study of Oral QLT091001 in Subjects With Leber Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP) Due to Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT) Mutations