RPE65

Summary

RPE65 (retinoid isomerohydrolase RPE65, HGNC:10294) is a protein-coding gene on chromosome 1p31.3, encoding Retinoid isomerohydrolase (Q16518). Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins.

The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital.

Source: NCBI Gene 6121 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RPE65-related recessive retinopathy (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 1,148 total — 172 pathogenic, 137 likely-pathogenic
• Phenotypes (HPO): 78
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10294
Approved symbol	RPE65
Name	retinoid isomerohydrolase RPE65
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	LCA2, rd12, BCO3
Ensembl gene	ENSG00000116745
Ensembl biotype	protein_coding
OMIM	180069
Entrez	6121

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 nonsense_mediated_decay, 1 protein_coding

ENST00000262340, ENST00000713936, ENST00000713937, ENST00000713938, ENST00000713939

RefSeq mRNA: 5 — MANE Select: NM_000329 NM_000329, NM_001406853, NM_001406856, NM_001406857, NM_001406859

CCDS: CCDS643

Canonical transcript exons

ENST00000262340 — 14 exons

Exon	Start	End
ENSE00000774483	68444776	68444883
ENSE00000774484	68444531	68444672
ENSE00000774485	68440853	68441000
ENSE00000774486	68439561	68439642
ENSE00000774493	68431471	68431585
ENSE00000774494	68431282	68431376
ENSE00000774495	68431065	68431176
ENSE00000956745	68439191	68439323
ENSE00000956746	68438942	68439081
ENSE00000956747	68438187	68438316
ENSE00001007068	68428822	68429927
ENSE00001066663	68446710	68446860
ENSE00001066665	68448624	68448706
ENSE00001362833	68449895	68449954

Expression profiles

Bgee: expression breadth broad, 92 present calls, max score 99.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7844 / max 2278.8325, expressed in 132 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12788	1.7664	132
12789	0.0180	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.80	gold quality
retina	UBERON:0000966	99.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.32	gold quality
cranial nerve II	UBERON:0000941	67.07	gold quality
choroid plexus epithelium	UBERON:0003911	66.72	gold quality
hypothalamus	UBERON:0001898	64.35	gold quality
substantia nigra	UBERON:0002038	62.39	gold quality
midbrain	UBERON:0001891	60.22	gold quality
decidua	UBERON:0002450	56.55	gold quality
eye	UBERON:0000970	56.24	silver quality
lower lobe of lung	UBERON:0008949	56.23	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	55.92	gold quality
spinal cord	UBERON:0002240	54.47	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
seminal vesicle	UBERON:0000998	52.40	silver quality
ventricular zone	UBERON:0003053	52.31	gold quality
corpus callosum	UBERON:0002336	52.26	gold quality
prostate gland	UBERON:0002367	51.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	50.61	gold quality
prefrontal cortex	UBERON:0000451	50.57	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	49.75	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
vastus lateralis	UBERON:0001379	49.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	5237.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MEF2C	Activation

Upstream regulators (CollecTRI, top): HR, LHX2, MEF2C, OTX2, POU2F1, SOX9, TFAP4, ZNF250, ZNF492

miRNA regulators (miRDB)

60 targeting RPE65, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-208A-5P	99.42	70.83	1913

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• demonstrated that the dTip60 chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av; both the histone acetyltransferase dTip60 and the atpase Domino/p400 catalyze the exchange of phospho-H2Av (PMID:15528408)
• TIP60 complex can promote the generation of silent chromatin. (PMID:16816423)
• TIP60 is differentially expressed during Drosophila development, with transcript levels significantly peaking during embryogenesis, and is essential for multicellular development. (PMID:17179074)
• Ubiquitous dTip60 knock-down in flies was lethal, whereas knock-down in the wing imaginal disk led to developmental defects. (PMID:19949809)
• The role of Tip60 HAT activity in transcriptional control during multicellular development in vivo, was investigated. (PMID:21494552)
• a functional interaction between Tip60 and APP in mediating nervous system development and apoptotic neuronal cell death (PMID:22848598)
• a novel mechanism for Tip60 mediated sleep-wake regulation via control of axonal growth and PDF levels within the small ventrolateral neurons-encompassing neural network (PMID:22982579)
• Excess Tip60 exerts a neuroprotective role in axonal transport and functional locomotion defects in an animal model of Alzheimer’s disease. (PMID:23616558)
• Heat Shock Factor recruits the dTip60 complex to the hsp70 loci in cells treated with salicylate, which triggers chromatin remodeling at these loci without transcription activation. (PMID:24639513)
• critical for morphology and function of the mushroom body (PMID:26327426)
• most HIF1A targets require either TIP60, the CDK8-Mediator complex, or both as coactivators for full expression in hypoxia. (PMID:27320910)
• Our results implicate Tip60 as a critical mediator of EE-induced benefits, and provide broad insights into synergistic behavioral and epigenetic based therapeutic approaches for treatment of cognitive disorder. (PMID:27454757)
• compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. (PMID:28196077)
• findings reveal an evolutionarily conserved functional link between Myc, the Tip60 complex, and the molecular network controlling cell polarity and asymmetric cell division. (PMID:29997178)
• Results indicate that Tip60 complex coordinates cell cycle progression and expression of bgcn to help drive GSC daughters toward a differentiation program. (PMID:30230973)
• heterozygosity for Enhancer of Polycomb [E(Pc)], a component of the Tip60 lysine acetyltransferase complex (also known as KAT5 in humans), significantly increased tumor burden in hop(Tum) animals. (PMID:31072879)
• Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A. (PMID:33087840)
• Tip60 protects against amyloid-beta-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegeneration. (PMID:33160016)
• In Vivo Silencing of Genes Coding for dTip60 Chromatin Remodeling Complex Subunits Affects Polytene Chromosome Organization and Proper Development in Drosophila melanogaster. (PMID:33926075)
• Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex. (PMID:34107298)
• Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain. (PMID:34369292)
• Tip60’s Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer’s Disease. (PMID:36849418)
• Knockdown of DOM/Tip60 Complex Subunits Impairs Male Meiosis of Drosophila melanogaster. (PMID:37408183)
• Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control. (PMID:37598897)
• novel mutations in patients with Leber congenital amaurosis (PMID:11462243)
• retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively (PMID:11727200)
• RPE65 mutations present in compound heterozygous form cause severe visual compromise. (PMID:11786058)
• multiplex PCR follwed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa and Leber’s congenital amaurosis patients (PMID:12357075)
• The RPE65 mutations K303X and Y431C in compound heterozygous form cause progressive visual compromise that starts in childhood and advances to severe visual loss by the fourth decade of life. (PMID:14962443)
• Colocalization of plasma retinol-binding protein with RPE65 and affinity binding suggest a direct interaction of RPE65 with plasma retinol-binding protein in cultured human keratinocytes that might be involved in retinoid uptake of keratinocytes. (PMID:15009723)
• Gene therapy with this protein to cure Leber congenital amaurosis; Gene therapy in Rpe65(-/-) mice at advanced-disease stages show some success (PMID:15837919)
• conserved glutamic acid and histidine residues are essential for the isomerohydrolase activity of RPE65 and its stability (PMID:16198348)
• AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 mutations may have roles in juvenile retinitis pigmentosa (PMID:16272259)
• We identified and characterised an endemic form of early onset rod-cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single RPE65 mutation. (PMID:16518657)
• mutations may result in critical structural alterations of RPE65 protein, disrupt its membrane association, and consequently impair its isomerohydrolase activity, leading to retinal degeneration (PMID:16754667)
• The results demand critical consideration of the human disease mechanism and the therapeutic approach in patients with mutations in the putative visual cycle gene RDH12. (PMID:17197551)
• Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution (PMID:17651254)
• RPE65 gene mutations represented a significant cause of LCA in the Italian population, whereas GUCY2D and CEP290 mutations had a lower frequency than that found in other reports. (PMID:17724218)
• Early cone photoreceptor losses in RPE65-LCA suggest that robust RPE65-based visual chromophore production is important for cones. (PMID:17848510)
• RPE65 from the cone-dominant chicken RPE possesses significantly higher specific retinol isomerohydrolase activity, when compared with RPE65 from rod-dominant species (PMID:18216020)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpe65a	ENSDARG00000007480
danio_rerio	rpe65c	ENSDARG00000054420
danio_rerio	rpe65b	ENSDARG00000094752
mus_musculus	Rpe65	ENSMUSG00000028174
rattus_norvegicus	Rpe65	ENSRNOG00000009582

Paralogs (2): BCO1 (ENSG00000135697), BCO2 (ENSG00000197580)

Protein

Protein identifiers

Retinoid isomerohydrolase — Q16518 (reviewed: Q16518)

Alternative names: All-trans-retinyl-palmitate hydrolase, Lutein isomerase, Meso-zeaxanthin isomerase, Retinal pigment epithelium-specific 65 kDa protein, Retinol isomerase

All UniProt accessions (5): Q16518, A0AAQ5BH46, A0AAQ5BH58, A0AAQ5BH62, A0AAQ5BH81

UniProt curated annotations — full annotation on UniProt →

Function. Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore. Essential for the production of 11-cis retinal for both rod and cone photoreceptors. Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT.

Subunit / interactions. Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.

Subcellular location. Cytoplasm. Cell membrane. Microsome membrane.

Tissue specificity. Retina (at protein level). Retinal pigment epithelium specific.

Post-translational modifications. Palmitoylation by LRAT regulates ligand binding specificity; the palmitoylated form (membrane form) specifically binds all-trans-retinyl-palmitate, while the soluble unpalmitoylated form binds all-trans-retinol (vitamin A).

Disease relevance. Leber congenital amaurosis 2 (LCA2) [MIM:204100] A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. The disease is caused by variants affecting the gene represented in this entry. Retinitis pigmentosa 20 (RP20) [MIM:613794] 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. Retinitis pigmentosa 87 with choroidal involvement (RP87) [MIM:618697] A form of retinitis pigmentosa, 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. RP87 is an autosomal dominant form characterized by a slowly progressive visual disturbance accompanied by extensive choroid/retinal atrophy that mimics certain aspects of choroideremia. Disease severity and age of onset are variable, and some carriers are unaffected. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Similarity. Belongs to the carotenoid oxygenase family.

RefSeq proteins (5): NP_000320, NP_001393782, NP_001393785, NP_001393786, NP_001393788 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004294	Carotenoid_Oase	Family

Pfam: PF03055

Enzyme classification (BRENDA):

• EC 3.1.1.64 — retinoid isomerohydrolase (BRENDA: 9 organisms, 32 substrates, 29 inhibitors, 7 Km, 2 kcat entries)
• EC 5.3.3.22 — lutein isomerase (BRENDA: 2 organisms, 1 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALL-TRANS-RETINYL PALMITATE	0.0036–0.045	4
AN ALL-TRANS RETINYL ESTER	0.0026	1
AN ALL-TRANS-RETINYL ESTER	0.001	1

Catalyzed reactions (Rhea), 3 shown:

• lutein = (3R,3’S)-zeaxanthin (RHEA:12729)
• an all-trans-retinyl ester + H2O = 11-cis-retinol + a fatty acid + H(+) (RHEA:31771)
• all-trans-retinyl hexadecanoate + H2O = 11-cis-retinol + hexadecanoate + H(+) (RHEA:31775)

UniProt features (90 total): sequence variant 57, mutagenesis site 16, modified residue 5, lipid moiety-binding region 4, binding site 4, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16518-F1	95.34	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 180; 241; 313; 527

Post-translational modifications (9): 117, 112, 231, 329, 330, 2, 101, 105, 113

Mutagenesis-validated functional residues (16):

Position	Phenotype
39	does not affect isomerohydrolase activity.
106	no loss of enzymatic activity. no effect on palmitoylation. no loss of membrane association.
106	does not affect isomerohydrolase activity.
112	loss of enzymatic activity. no palmitoylation. loss of membrane association.
170	increased isomerohydrolase activity.
180	loss of enzymatic activity.
241	decreasing protein levels. loss of enzymatic activity. significantly decreased protein stability.
297	increased isomerohydrolase activity.
313	decreasing protein levels. loss of enzymatic activity. significantly decreased protein stability.
330	does not affect isomerohydrolase activity.
469	decreasing protein levels. loss of enzymatic activity.
497	does not affect isomerohydrolase activity.
510	does not affect isomerohydrolase activity.
527	decreasing protein levels. loss of enzymatic activity. significantly decreased protein stability.
533	does not affect isomerohydrolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-2187338	Visual phototransduction
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 271 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, PID_CONE_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_INSULIN, NF1_Q6_01, BRN2_01

GO Biological Process (13): retinoid metabolic process (GO:0001523), retina homeostasis (GO:0001895), neural retina development (GO:0003407), vitamin A metabolic process (GO:0006776), visual perception (GO:0007601), circadian rhythm (GO:0007623), retinal metabolic process (GO:0042574), detection of light stimulus involved in visual perception (GO:0050908), zeaxanthin biosynthetic process (GO:1901827), lipid metabolic process (GO:0006629), response to light stimulus (GO:0009416), retinol metabolic process (GO:0042572), camera-type eye development (GO:0043010)

GO Molecular Function (12): phosphatidylserine binding (GO:0001786), beta-carotene 15,15’-dioxygenase activity (GO:0003834), isomerase activity (GO:0016853), phosphatidylcholine binding (GO:0031210), metal ion binding (GO:0046872), retinol isomerase activity (GO:0050251), all-trans-retinyl-palmitate hydrolase, 11-cis retinol forming activity (GO:0052884), all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity (GO:0052885), cardiolipin binding (GO:1901612), protein binding (GO:0005515), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleus (GO:0005634), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), cell body (GO:0044297), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Visual phototransduction	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid metabolic process	3
cellular anatomical structure	3
olefinic compound metabolic process	2
phospholipid binding	2
catalytic activity	2
cation binding	2
intracellular membrane-bounded organelle	2
diterpenoid metabolic process	1
tissue homeostasis	1
anatomical structure development	1
retina development in camera-type eye	1
sensory perception of light stimulus	1
rhythmic process	1
aldehyde metabolic process	1
visual perception	1
detection of light stimulus involved in sensory perception	1
xanthophyll biosynthetic process	1
primary metabolic process	1
response to radiation	1
primary alcohol metabolic process	1
hormone metabolic process	1
eye development	1
anion binding	1
modified amino acid binding	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	1
quaternary ammonium group binding	1
cis-trans isomerase activity	1
retinyl-palmitate esterase activity	1
retinol metabolic process	1
carboxylic ester hydrolase activity	1
phosphatidylglycerol binding	1
binding	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	1
dioxygenase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPE65	LRAT	O95237	976
RPE65	RDH12	Q96NR8	932
RPE65	RLBP1	P12271	925
RPE65	TULP1	O00294	918
RPE65	RHO	P08100	912
RPE65	AIPL1	Q9NZN9	902
RPE65	MERTK	Q12866	896
RPE65	BEST1	O76090	892
RPE65	GUCY2D	Q02846	882
RPE65	CRX	O43186	875
RPE65	GNAT1	P11488	873
RPE65	CNGA3	Q16281	870
RPE65	ABCA4	P78363	867
RPE65	RPGRIP1	Q96KN7	861
RPE65	SPATA7	Q9P0W8	857

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RPE65	CCT6B	psi-mi:“MI:0915”(physical association)	0.620
RPE65	CCT3	psi-mi:“MI:0914”(association)	0.350
RPE65	CCT2	psi-mi:“MI:0914”(association)	0.350
MYO7A	RPE65	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (13): ZMYM2 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT3 (Affinity Capture-MS), RPE65 (Affinity Capture-MS), RPE65 (Synthetic Lethality), CCT2 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), RPE65 (Co-fractionation), SLC27A1 (Two-hybrid), SLC27A1 (Affinity Capture-Western), SLC27A1 (Reconstituted Complex), RPE65 (Affinity Capture-Western)

ESM2 similar proteins: A0A2R8QP51, A0A3L7I2I8, A5PK39, A8WGE3, A8Y9I2, A9C3R8, A9C3R9, C3VEQ3, C3VEQ4, G1SPE9, K4CJJ1, O24023, O49505, O60733, O65572, O70276, P29144, P97570, P97819, Q16518, Q28175, Q2KJA6, Q4R5Z4, Q4R678, Q5ZKK2, Q64514, Q64560, Q6DJD8, Q6PBW5, Q80YV4, Q84KG5, Q86TI2, Q8AXN9, Q8BVG4, Q8K114, Q8LP17, Q91XT5, Q91ZQ5, Q94IR2, Q9C6Z1

Diamond homologs: A8Y9I2, A9C3R8, A9C3R9, O70276, Q16518, Q28175, Q5RF16, Q6PBW5, Q6QT07, Q8AXN9, Q8HXG8, Q91XT5, Q91ZQ5, Q99NF1, Q9BYV7, Q9HAY6, Q9I993, Q9JJS6, Q9TVB8, Q9VFS2, Q9XT71, Q9YGX2, Q9YI25, Q93VD5, Q8VY26

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1148 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	172
Likely pathogenic	137
Uncertain significance	353
Likely benign	384
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067786	NM_000329.3(RPE65):c.496-1G>A	Pathogenic
1068757	NM_000329.3(RPE65):c.200T>G (p.Leu67Arg)	Pathogenic
1068758	NM_000329.3(RPE65):c.94G>T (p.Gly32Cys)	Pathogenic
1069087	NM_000329.3(RPE65):c.943_950del (p.Ile315fs)	Pathogenic
1069898	NM_000329.3(RPE65):c.1399C>G (p.Pro467Ala)	Pathogenic
1070755	NM_000329.3(RPE65):c.886dup (p.Arg296fs)	Pathogenic
1072065	NM_000329.3(RPE65):c.777dup (p.Asn260Ter)	Pathogenic
1072114	NM_000329.3(RPE65):c.1028T>G (p.Leu343Ter)	Pathogenic
1074826	NM_000329.3(RPE65):c.545A>G (p.His182Arg)	Pathogenic
1076977	NC_000001.10:g.(?68912383)(68912553_?)del	Pathogenic
1213911	NM_000329.3(RPE65):c.1443del (p.Asp482fs)	Pathogenic
1213913	NM_000329.3(RPE65):c.693C>A (p.Cys231Ter)	Pathogenic
1213914	NM_000329.3(RPE65):c.1451-2del	Pathogenic
1213916	NM_000329.3(RPE65):c.1229C>A (p.Ser410Ter)	Pathogenic
1213917	NM_000329.3(RPE65):c.859del	Pathogenic
1213919	NM_000329.3(RPE65):c.785_787del (p.Phe262_Lys263delinsTer)	Pathogenic
13114	NM_000329.3(RPE65):c.700C>T (p.Arg234Ter)	Pathogenic
13115	NM_000329.3(RPE65):c.271C>T (p.Arg91Trp)	Pathogenic
13117	NM_000329.3(RPE65):c.1087C>A (p.Pro363Thr)	Pathogenic
13118	NM_000329.3(RPE65):c.1022T>C (p.Leu341Ser)	Pathogenic
13120	NM_000329.3(RPE65):c.1543C>T (p.Arg515Trp)	Pathogenic
1321180	NM_000329.3(RPE65):c.1451-1G>A	Pathogenic
1355343	NM_000329.3(RPE65):c.46_49del (p.Phe16fs)	Pathogenic
1380598	NM_000329.3(RPE65):c.775dup (p.Ile259fs)	Pathogenic
1381188	NM_000329.3(RPE65):c.504_580del (p.Cys169fs)	Pathogenic
1384701	NM_000329.3(RPE65):c.1501_1505del (p.Tyr501fs)	Pathogenic
1416497	NM_000329.3(RPE65):c.644-2A>C	Pathogenic
1429329	NM_000329.3(RPE65):c.1115dup (p.Leu372fs)	Pathogenic
1445004	NM_000329.3(RPE65):c.1580A>G (p.His527Arg)	Pathogenic
1452221	NM_000329.3(RPE65):c.528_529del (p.Ala177fs)	Pathogenic

SpliceAI

1712 predictions. Top by Δscore:

Variant	Effect	Δscore
1:68431586:C:CC	acceptor_gain	1.0000
1:68438940:AC:A	donor_gain	1.0000
1:68438941:CC:C	donor_gain	1.0000
1:68439083:T:C	acceptor_gain	1.0000
1:68439290:C:CT	acceptor_gain	1.0000
1:68439319:CAAAA:C	acceptor_gain	1.0000
1:68439324:C:CC	acceptor_gain	1.0000
1:68449891:TTA:T	donor_loss	1.0000
1:68449892:TAC:T	donor_loss	1.0000
1:68449893:A:AC	donor_gain	1.0000
1:68449893:AC:A	donor_loss	1.0000
1:68449894:C:CT	donor_gain	1.0000
1:68449894:CT:C	donor_gain	1.0000
1:68449894:CTG:C	donor_gain	1.0000
1:68449894:CTGG:C	donor_gain	1.0000
1:68449894:CTGGA:C	donor_gain	1.0000
1:68431177:C:CC	acceptor_gain	0.9900
1:68431181:T:TC	acceptor_gain	0.9900
1:68431582:CAGC:C	acceptor_gain	0.9900
1:68431584:GC:G	acceptor_gain	0.9900
1:68431584:GCC:G	acceptor_loss	0.9900
1:68431585:CC:C	acceptor_gain	0.9900
1:68431585:CCT:C	acceptor_loss	0.9900
1:68431586:C:CG	acceptor_loss	0.9900
1:68438214:T:C	donor_gain	0.9900
1:68439080:ACC:A	acceptor_loss	0.9900
1:68439081:CC:C	acceptor_loss	0.9900
1:68439081:CCT:C	acceptor_gain	0.9900
1:68439082:C:CA	acceptor_loss	0.9900
1:68439083:T:G	acceptor_loss	0.9900

AlphaMissense

3522 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:68439323:A:C	S242R	1.000
1:68439323:A:T	S242R	1.000
1:68439562:T:G	S242R	1.000
1:68446770:T:A	D62V	1.000
1:68429799:G:C	H527D	0.999
1:68429834:C:G	R515P	0.999
1:68429914:A:C	S488R	0.999
1:68429914:A:T	S488R	0.999
1:68429916:T:G	S488R	0.999
1:68438953:G:C	C329W	0.999
1:68439003:G:C	H313D	0.999
1:68439561:C:A	S242I	0.999
1:68439563:A:C	H241Q	0.999
1:68439563:A:T	H241Q	0.999
1:68439565:G:C	H241D	0.999
1:68440958:G:C	H180D	0.999
1:68440960:G:T	A179D	0.999
1:68444583:T:A	E148V	0.999
1:68444633:A:C	N131K	0.999
1:68444633:A:T	N131K	0.999
1:68444818:C:T	G104D	0.999
1:68444820:A:C	F103L	0.999
1:68444820:A:T	F103L	0.999
1:68444822:A:G	F103L	0.999
1:68444855:C:G	A92P	0.999
1:68446767:C:T	G63E	0.999
1:68446768:C:A	G63W	0.999
1:68446771:C:A	D62Y	0.999
1:68446771:C:G	D62H	0.999
1:68446772:A:C	F61L	0.999

dbSNP variants (sampled 300 via entrez): RS1000192263 (1:68444159 A>G), RS1000375674 (1:68432513 AG>A), RS1000435208 (1:68443960 G>C), RS1001171788 (1:68433006 G>A), RS1001234263 (1:68442436 G>A,C), RS1001493648 (1:68449533 T>A), RS1001966191 (1:68430750 C>T), RS1002142406 (1:68436759 C>T), RS1002203191 (1:68446015 T>A), RS1002234158 (1:68445686 C>T), RS1002315346 (1:68430443 T>A,C), RS1002574197 (1:68447277 T>C), RS1002623606 (1:68447509 T>C), RS1002783231 (1:68447802 A>G), RS1002809522 (1:68434636 G>A)

Disease associations

OMIM: gene MIM:180069 | disease phenotypes: MIM:204100, MIM:613794, MIM:204000, MIM:618697, MIM:613660, MIM:268000, MIM:120970, MIM:201400, MIM:209850, MIM:612285

GenCC curated gene-disease

Disease	Classification	Inheritance
RPE65-related recessive retinopathy	Definitive	Autosomal recessive
Leber congenital amaurosis 2	Definitive	Autosomal recessive
retinitis pigmentosa	Definitive	Autosomal recessive
retinitis pigmentosa 20	Strong	Autosomal recessive
RPE65-related dominant retinopathy	Strong	Autosomal dominant
severe early-childhood-onset retinal dystrophy	Supportive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant
retinitis pigmentosa 87 with choroidal involvement	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
RPE65-related recessive retinopathy	Definitive	AR
RPE65-related dominant retinopathy	Strong	AD

Mondo (18): Leber congenital amaurosis 2 (MONDO:0008765), retinitis pigmentosa 20 (MONDO:0013425), Leber congenital amaurosis (MONDO:0018998), RPE65-related recessive retinopathy (MONDO:0100368), retinitis pigmentosa 87 with choroidal involvement (MONDO:0032873), cone-rod dystrophy 15 (MONDO:0013348), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), retinal degeneration (MONDO:0004580), cone-rod dystrophy (MONDO:0015993), congenital isolated adrenocorticotropic hormone deficiency (MONDO:0008720), retinal disorder (MONDO:0005283), neurodevelopmental disorder (MONDO:0700092), pathologic nystagmus (MONDO:0004843), autism (MONDO:0005260)

Orphanet (6): Leber congenital amaurosis (Orphanet:65), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Cone rod dystrophy (Orphanet:1872), Congenital isolated ACTH deficiency (Orphanet:199296), Joubert syndrome with oculorenal defect (Orphanet:2318)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
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:0000518	Cataract
HP:0000533	Chorioretinal atrophy
HP:0000540	Hypermetropia
HP:0000541	Retinal detachment
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000577	Exotropia
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000622	Blurred vision
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior
HP:0000842	Hyperinsulinemia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003817_1	Mortality in sepsis	3.000000e-06
GCST004075_42	Vertical cup-disc ratio	3.000000e-08
GCST004075_43	Vertical cup-disc ratio	2.000000e-07
GCST009464_11	Facial morphology	8.000000e-09
GCST009464_37	Facial morphology	3.000000e-08
GCST009723_61	Vertical cup-disc ratio (adjusted for vertical disc diameter)	5.000000e-14
GCST009724_83	Vertical cup-disc ratio (multi-trait analysis)	1.000000e-10
GCST009724_84	Vertical cup-disc ratio (multi-trait analysis)	4.000000e-20
GCST011743_83	HDL cholesterol levels in HIV infection	6.000000e-06
GCST90011770_28	Glaucoma (primary open-angle)	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0006939	cup-to-disc ratio measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D065886	Neurodevelopmental Disorders	F03.625
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D012162	Retinal Degeneration	C11.270.612; C11.768.585
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
C535668	Adrenocorticotropic hormone deficiency (supp.)
C536601	Amaurosis congenita of Leber, type 2 (supp.)
C567364	Joubert Syndrome 9 (supp.)
C566718	Retinitis Pigmentosa 20 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831182 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

129 measured of 147 human assays (168 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(3-(2-Propylpentyloxy)Phenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-((3-(3-Aminopropyl)Phenoxy)Methyl)Pentan-3-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(2-Ethylbutoxy)Phenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(Benzyloxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(Isopentyloxy)Phenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-Phenethoxyphenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1R,2R)-2-(Aminomethyl)-1-(3-(Cyclohexylmethoxy)Phenyl)Butan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-Phenethoxyphenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(S)-1-Amino-3-(3-(2-Ethylbutoxy)Phenyl)Propan-2-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(S)-1-Amino-3-(3-(2-Propylpentyloxy)Phenyl)Propan-2-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(R)-1-Amino-3-(3-(2-Propylpentyloxy)Phenyl)Propan-2-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(R)-1-Amino-3-(3-(2-Ethylbutoxy)Phenyl)Propan-2-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(Cyclopropylmethoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1S,2S)-3-Amino-1-(3-(Cyclohexylmethoxy)Phenyl)-2-Methylpropan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1R,2S)-3-Amino-1-(3-(Cyclohexylmethoxy)Phenyl)-2-Methylpropan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(Cyclohexylmethoxy)Phenyl)Butan-1-Amine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-((Tetrahydro-2H-Pyran-2-Yl)Methoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(Pentyloxy)Phenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(2-Methoxybenzyloxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(Cyclooctylmethoxy)Phenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(Cyclopentylmethoxy)Phenyl)Propan-1-Amine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(Cyclopentylmethoxy)Phenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(2,6-Dichlorobenzyloxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(Cyclooctylmethoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(Isopentyloxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(3-Methoxypropoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(4-(Benzyloxy)Butoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(5-(Benzyloxy)Pentyloxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(Cyclohexylmethoxy)Phenylthio)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(Cyclohexylmethoxy)Phenyl)-3-Hydroxypropanimidamide	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(3-(Benzyloxy)Propoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1,2-Cis)-2-((3-(3-Aminopropyl)Phenoxy)Methyl)Cyclohexanol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1,2-Trans)-2-((3-(3-Aminopropyl)Phenoxy)Methyl)Cyclohexanol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
2-(3-(Cyclohexylmethoxy)-5-Methylphenoxy)Ethanamine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
1-(3-(3-Amino-1-Hydroxypropyl)Phenoxy)-3-Methylbutan-2-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-Amino-1-(3-(2-Hydroxy-2-Phenylethoxy)Phenyl)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
1-(3-(3-Amino-1-Hydroxypropyl)Phenoxy)Pentan-2-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
5-(3-(3-Amino-1-Hydroxypropyl)Phenoxy)Pentan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1,2-Trans)-2-((3-((R)-3-Amino-1-Hydroxypropyl)Phenoxy)Methyl)Cyclohexyl Acetate	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1,2-Cis)-2-((3-((R)-3-Amino-1-Hydroxypropyl)Phenoxy)Methyl)Cyclohexyl Acetate	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1S,2S)-3-Amino-1-(3-(Cyclohexylmethoxy)Phenyl)Propane-1,2-Diol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(R)-3-(3-Amino-1-Hydroxypropyl)-5-(Cyclohexylmethoxy)Phenol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
(1S,2R)-3-Amino-1-(3-(Cyclohexylmethoxy)Phenyl)Propane-1,2-Diol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
1-(3-(Cyclohexylmethoxy)Phenyl)-3-(Methylamino)Propan-1-Ol	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(Cyclohexylmethoxy)Phenyl)-3-Fluoropropan-1-Amine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(Cyclohexylmethoxy)Phenyl)Prop-2-Yn-1-Amine	IC50	55 nM	US-10188615: Alkoxy compounds for disease treatment
1-((3-(2-Aminoethoxy)Phenoxy)Methyl)Cyclohexanol	IC50	550 nM	US-10188615: Alkoxy compounds for disease treatment
3-((3-(2-Aminoethoxy)Phenoxy)Methyl)Pentan-3-Ol	IC50	550 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(Isopentyloxy)Phenyl)Propan-1-Amine	IC50	550 nM	US-10188615: Alkoxy compounds for disease treatment
3-(3-(2-Methoxybenzyloxy)Phenyl)Propan-1-Amine	IC50	550 nM	US-10188615: Alkoxy compounds for disease treatment

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases expression	2
Vitamin A	increases chemical synthesis, increases metabolic processing	2
methylmercuric chloride	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases expression	1
Copper	affects cotreatment, increases expression	1
Retinaldehyde	increases chemical synthesis	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

7 cell lines: 7 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B5T7	SCTCi016-A	Induced pluripotent stem cell	Female
CVCL_D0HQ	LVPEIi004-A	Induced pluripotent stem cell	Male
CVCL_D6MU	LVPEIi005-A	Induced pluripotent stem cell	Male
CVCL_E4X9	LVPEIi005-A-1	Induced pluripotent stem cell	Male
CVCL_YC17	NUIGi027-A	Induced pluripotent stem cell	Male
CVCL_YC18	NUIGi028-A	Induced pluripotent stem cell	Male
CVCL_YC19	NUIGi029-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

277 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
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
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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
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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)