RD3

Summary

RD3 (RD3 regulator of GUCY2D, HGNC:19689) is a protein-coding gene on chromosome 1q32.3, encoding Protein RD3 (Q7Z3Z2). Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors.

This gene encodes a retinal protein that is associated with promyelocytic leukemia-gene product (PML) bodies in the nucleus. Mutations in this gene cause Leber congenital amaurosis type 12, a disease that results in retinal degeneration. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 343035 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RD3-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 254 total — 13 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_001164688

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19689
Approved symbol	RD3
Name	RD3 regulator of GUCY2D
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	LCA12
Ensembl gene	ENSG00000198570
Ensembl biotype	protein_coding
OMIM	180040
Entrez	343035

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367002, ENST00000484910, ENST00000680073, ENST00000904292, ENST00000927116, ENST00000961406

RefSeq mRNA: 2 — MANE Select: NM_001164688 NM_001164688, NM_183059

CCDS: CCDS1498

Canonical transcript exons

ENST00000680073 — 3 exons

Exon	Start	End
ENSE00001443212	211491768	211492162
ENSE00003662277	211476522	211479327
ENSE00003912460	211481120	211481426

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 87.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7306 / max 1523.7627, expressed in 67 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17342	1.3738	49
17341	0.3493	48
17343	0.0075	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.11	gold quality
buccal mucosa cell	CL:0002336	68.45	silver quality
right lung	UBERON:0002167	55.20	gold quality
pigmented layer of retina	UBERON:0001782	53.85	gold quality
cerebellar vermis	UBERON:0004720	53.75	gold quality
myocardium	UBERON:0002349	53.30	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	52.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	51.99	gold quality
lower esophagus	UBERON:0013473	51.83	gold quality
sperm	CL:0000019	51.81	gold quality
body of stomach	UBERON:0001161	50.23	gold quality
pituitary gland	UBERON:0000007	50.01	gold quality
ectocervix	UBERON:0012249	49.96	gold quality
lower lobe of lung	UBERON:0008949	49.25	silver quality
stromal cell of endometrium	CL:0002255	48.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	48.02	gold quality
lower esophagus mucosa	UBERON:0035834	47.84	gold quality
small intestine	UBERON:0002108	47.51	gold quality
smooth muscle tissue	UBERON:0001135	47.39	gold quality
ventricular zone	UBERON:0003053	47.35	silver quality
left uterine tube	UBERON:0001303	47.31	gold quality
body of uterus	UBERON:0009853	47.27	gold quality
esophagus	UBERON:0001043	47.12	gold quality
stomach	UBERON:0000945	46.93	gold quality
fundus of stomach	UBERON:0001160	46.28	gold quality
adenohypophysis	UBERON:0002196	46.03	gold quality
urinary bladder	UBERON:0001255	45.84	gold quality
transverse colon	UBERON:0001157	44.99	gold quality
uterine cervix	UBERON:0000002	44.98	gold quality
upper lobe of lung	UBERON:0008948	44.43	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting RD3, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-670-5P	99.67	69.94	1565

Literature-anchored findings (GeneRIF, showing 9)

• Identification and sequence analysis of C1orf36. (PMID:12914764)
• the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing. (PMID:17186464)
• RD3 suppresses the basal catalytic activity of guanylyl cyclase activating proteins (GCAP) in a noncompetitive manner. (PMID:21928830)
• Mutations in RD3 are a very rare cause of Leber’s congenital amaurosis (LCA) associated with an extremely severe form of retinal dystrophy. (PMID:22531706)
• This study reports the results of an international study aimed at delineating the clinical and molecular spectrum of RD3 mutations in retinal dystrophies. (PMID:23308101)
• Re-expressing RD3 in metastatic site-derived aggressive cells reverted their metastatic potential both in vitro and in vivo. Conversely muting RD3 in neuroblastoma cells not only heightened invasion/migration but also dictated aggressive disease with metastasis. (PMID:26375249)
• Study stratified expression of RD3 in different cell types and subcellular location of retina. We demonstrated extensive positive RD3 immunoreactivity in various normal tissues and particularly strong dot-like perinuclear staining in the lining epithelial cells, suggesting that RD3 may play an important role in the normal functioning of epithelial cells. RD3 expression is limited in the CNS. (PMID:29030614)
• The NMR structure of RD3 presented here provides a structural basis for elucidating RD3-RetGC interactions relevant for normal vision or blindness. (PMID:30559291)
• Two clusters of surface-exposed amino acid residues enable high-affinity binding of retinal degeneration-3 (RD3) protein to retinal guanylyl cyclase. (PMID:32493772)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rd3	ENSDARG00000031600
mus_musculus	Rd3	ENSMUSG00000049353
rattus_norvegicus	Rd3	ENSRNOG00000050766

Paralogs (1): RD3L (ENSG00000227729)

Protein

Protein identifiers

Protein RD3 — Q7Z3Z2 (reviewed: Q7Z3Z2)

Alternative names: Retinal degeneration protein 3

All UniProt accessions (1): Q7Z3Z2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors. Inhibits the basal catalytic activity and the GCAP-stimulated activity of GUCY2D and GUCY2F, two retinal guanylyl cyclases involved in the production of cGMP in photoreceptors. Involved in the transport of GUCY2D and GUCY2F to their target sites in the photoreceptor outer segment. Up-regulates the activity of GUK1, a kinase that also plays an essential role for recycling GMP and indirectly, cGMP. Plays an important role for the survival of rods and cones in the retina.

Subunit / interactions. Monomer. Interacts with GUCY2D; negatively regulates its activity. The interaction with GUCY2D promotes the exit of GUCY2D from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments. Interacts with GUCY2F. The interaction with GUCY2F negatively regulates GUCY2F activity. The interaction with GUCY2F promotes the exit of GUCY2F from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments. Interacts with GUK1; up-regulates GUK1 activity.

Subcellular location. Cell projection. Cilium. Photoreceptor outer segment. Photoreceptor inner segment. Endosome. Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in retina. Widely expressed (at protein level). In the retina the strongest immunoreactivity is detected in the inner half of the cytoplasmic portion of the photoreceptor layer, where rods and cones are found, and the external half of the outer plexiform layer (at protein level).

Disease relevance. Leber congenital amaurosis 12 (LCA12) [MIM:610612] 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.

RefSeq proteins (2): NP_001158160, NP_898882 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028092	RD3	Family

Pfam: PF14473

UniProt features (29 total): mutagenesis site 10, sequence variant 9, helix 6, chain 1, region of interest 1, coiled-coil region 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6DRF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3Z2-F1	80.99	0.52

Functional residue map

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

Mutagenesis-validated functional residues (10):

Position	Phenotype
29	reduced the affinity of rd3 for gucy2d.
32	reduced the affinity of rd3 for gucy2d.
85	reduced the affinity of rd3 for gucy2d.
87–90	strongly affects rd3 ability to suppress gucy2d activity.
93–97	strongly affects rd3 ability to suppress gucy2d activity.
93	reduced rd3 affinity for gucy2d by 80-fold.
93	increased the affinity of rd3 for gucy2d.
99–102	strongly affects rd3 ability to suppress gucy2d activity.
108	does not affect affinity of rd3 for gucy2d.
119–122	strongly affects rd3 ability to suppress gucy2d activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 147 (showing top): GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_NEGATIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_REGULATION_OF_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOBP_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS

GO Biological Process (4): visual perception (GO:0007601), protein transport (GO:0015031), negative regulation of guanylate cyclase activity (GO:0031283), retina development in camera-type eye (GO:0060041)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), perinuclear region of cytoplasm (GO:0048471), cone photoreceptor outer segment (GO:0120199), rod photoreceptor outer segment (GO:0120200), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
photoreceptor outer segment	2
sensory perception of light stimulus	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
guanylate cyclase activity	1
negative regulation of catalytic activity	1
negative regulation of purine nucleotide biosynthetic process	1
camera-type eye development	1
anatomical structure development	1
binding	1
photoreceptor cell cilium	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
cytoplasm	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RD3	PDE6B	P35913	913
RD3	GUCY2D	Q02846	903
RD3	SPATA7	Q9P0W8	892
RD3	PRPH2	P23942	885
RD3	LCA5	Q86VQ0	872
RD3	AIPL1	Q9NZN9	863
RD3	RPGRIP1	Q96KN7	860
RD3	RDH12	Q96NR8	852
RD3	RPE65	Q16518	840
RD3	LRAT	O95237	839
RD3	GUCA1A	P43080	834
RD3	IMPDH1	P20839	824
RD3	CEP290	O15078	807
RD3	CRX	O43186	794
RD3	TULP1	O00294	776

IntAct

28 interactions, top by confidence:

A	B	Type	Score
RD3	EIF2B1	psi-mi:“MI:0915”(physical association)	0.780
EIF2B1	RD3	psi-mi:“MI:0915”(physical association)	0.780
EHMT2	RD3	psi-mi:“MI:0915”(physical association)	0.560
RD3	EHMT2	psi-mi:“MI:0915”(physical association)	0.560
RD3	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
RD3	CABP2	psi-mi:“MI:0915”(physical association)	0.560
RD3	GUCY2D	psi-mi:“MI:0915”(physical association)	0.460
GUCY2D	RD3	psi-mi:“MI:0915”(physical association)	0.460
GUCY2D	RD3	psi-mi:“MI:0403”(colocalization)	0.460
RD3	GNAZ	psi-mi:“MI:0914”(association)	0.350
RD3	LRBA	psi-mi:“MI:0914”(association)	0.350
RD3	EIF2B1	psi-mi:“MI:0915”(physical association)	0.000
RD3	EHMT2	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	RD3	psi-mi:“MI:0915”(physical association)	0.000
CABP2	RD3	psi-mi:“MI:0915”(physical association)	0.000
EIF2B1	RD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): RD3 (Two-hybrid), RD3 (Two-hybrid), NBEA (Affinity Capture-MS), LRBA (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), GNA13 (Affinity Capture-MS), GNB4 (Affinity Capture-MS), CSNK1G3 (Affinity Capture-MS), RAP1B (Affinity Capture-MS), NDUFAF7 (Affinity Capture-MS), NBEA (Affinity Capture-MS), LRBA (Affinity Capture-MS), NDUFAF7 (Affinity Capture-MS), GNAZ (Affinity Capture-MS), RD3 (Two-hybrid)

ESM2 similar proteins: A0A1B0GVB3, A2RRY8, A4D263, A5LFW8, A5PJD8, A6H6Q4, A6NCJ1, A8IVJ1, A9CB94, C9J302, E1B9I5, O12165, O74317, O75603, O95561, P05902, P05903, P0C9Z6, P0CJ62, P10260, P10261, P27579, P36353, Q00111, Q0P670, Q2HR73, Q2KIR0, Q2M2T2, Q32KT7, Q32LJ5, Q3KPS4, Q3TTI8, Q496A3, Q4V7B2, Q5EG65, Q5NC83, Q68FQ8, Q6PKN7, Q6ZNM6, Q75EZ5

Diamond homologs: P0DJH9, Q7Z3Z2, Q8BRE0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	2
Uncertain significance	166
Likely benign	48
Benign	13

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
13121	NM_001164688.2(RD3):c.296+1G>A	Pathogenic
1388540	NM_001164688.2(RD3):c.296+1G>T	Pathogenic
189791	NM_001164688.2(RD3):c.180C>A (p.Tyr60Ter)	Pathogenic
189792	NM_001164688.2(RD3):c.112C>T (p.Arg38Ter)	Pathogenic
189793	NM_001164688.2(RD3):c.137_138del (p.Glu46fs)	Pathogenic
189794	NM_001164688.2(RD3):c.136G>T (p.Glu46Ter)	Pathogenic
2003233	NM_001164688.2(RD3):c.38del (p.Pro13fs)	Pathogenic
2106862	NM_001164688.2(RD3):c.238C>T (p.Gln80Ter)	Pathogenic
2427618	NC_000001.10:g.(?211652378)(211654757_?)del	Pathogenic
3248938	NM_001164688.2(RD3):c.346del (p.Gln116fs)	Pathogenic
3663320	NM_001164688.2(RD3):c.80_102del (p.Glu27fs)	Pathogenic
4077377	NM_001164688.2(RD3):c.296+641_*606del	Pathogenic
688555	GRCh37/hg19 1q32.3(chr1:211618004-211660264)x1	Pathogenic
3578445	NM_001164688.2(RD3):c.265del (p.His89fs)	Likely pathogenic
4077376	NM_001164688.2(RD3):c.394G>T (p.Glu132Ter)	Likely pathogenic

SpliceAI

830 predictions. Top by Δscore:

Variant	Effect	Δscore
1:211481114:GCTCA:G	donor_loss	0.9800
1:211481115:CTCA:C	donor_loss	0.9800
1:211481116:TCA:T	donor_loss	0.9800
1:211481117:CACC:C	donor_loss	0.9800
1:211481118:ACC:A	donor_loss	0.9800
1:211481119:C:G	donor_loss	0.9800
1:211480740:G:T	donor_gain	0.9700
1:211481159:A:C	donor_gain	0.9600
1:211481399:C:CT	acceptor_gain	0.9600
1:211481394:G:T	acceptor_gain	0.9500
1:211481171:T:TA	donor_gain	0.9400
1:211480172:CA:C	donor_gain	0.9300
1:211479325:AACC:A	acceptor_loss	0.9200
1:211479326:ACC:A	acceptor_loss	0.9200
1:211479328:C:CG	acceptor_loss	0.9200
1:211480741:A:AC	donor_gain	0.9200
1:211480742:C:CC	donor_gain	0.9200
1:211491861:A:T	acceptor_gain	0.9200
1:211481393:C:CT	acceptor_gain	0.9100
1:211481112:GTGCT:G	donor_loss	0.9000
1:211481400:A:C	acceptor_gain	0.9000
1:211479328:C:A	acceptor_gain	0.8700
1:211491860:C:CT	acceptor_gain	0.8700
1:211479326:ACCTG:A	acceptor_gain	0.8600
1:211480159:T:TA	donor_gain	0.8400
1:211480737:T:TA	donor_gain	0.8400
1:211484365:G:T	donor_gain	0.8400
1:211479328:C:CC	acceptor_gain	0.8300
1:211479325:AACCT:A	acceptor_gain	0.8200
1:211481399:C:T	acceptor_gain	0.8200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008746 (1:211485106 G>A), RS1000170708 (1:211481200 G>A,T), RS1000231852 (1:211490517 G>A,C,T), RS1000431956 (1:211480918 C>T), RS1000839462 (1:211490165 G>A), RS1000953716 (1:211486271 A>G), RS1001168622 (1:211482345 T>A), RS1001242641 (1:211478259 T>C), RS1001289482 (1:211491305 C>A,T), RS1001506295 (1:211489452 T>A), RS1001567626 (1:211483426 G>A), RS1001577974 (1:211493177 G>A), RS1001678724 (1:211483614 G>A), RS1001909984 (1:211491949 G>A), RS1001941363 (1:211492193 GC>G)

Disease associations

OMIM: gene MIM:180040 | disease phenotypes: MIM:610612, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis 12	Definitive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
RD3-related retinopathy	Definitive	AR

Mondo (3): Leber congenital amaurosis 12 (MONDO:0012525), Leber congenital amaurosis (MONDO:0018998), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Leber congenital amaurosis (Orphanet:65), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

28 total (29 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000563	Keratoconus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000729	Autistic behavior
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001483	Eye poking
HP:0002084	Encephalocele
HP:0002269	Abnormality of neuronal migration
HP:0004374	Hemiplegia/hemiparesis
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis
HP:0007703	Abnormal retinal pigmentation
HP:0007875	Congenital blindness
HP:0008002	Abnormal macular pigmentation
HP:0012426	Optic disc drusen
HP:0012795	Abnormal optic disc morphology
HP:0030211	Slow pupillary light response
HP:0030466	Abnormal full-field electroretinogram
HP:0000556	Retinal dystrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001854_1	Retinopathy in non-diabetics	4.000000e-06
GCST005316_314	Intelligence (MTAG)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658
C565697	Leber Congenital Amaurosis 12 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	increases methylation	2
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
benzo(e)pyrene	increases methylation	1
entinostat	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Permethrin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D6M4	LVPEIi006-A	Induced pluripotent stem cell	Male
CVCL_D6MZ	LVPEIi006-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03913143	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT00749957	PHASE1/PHASE2	COMPLETED	Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
NCT01208389	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
NCT01496040	PHASE1/PHASE2	COMPLETED	Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65
NCT02781480	PHASE1/PHASE2	COMPLETED	Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)
NCT03913130	PHASE1/PHASE2	TERMINATED	Extension Study to Study PQ-110-001 (NCT03140969)
NCT03920007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D
NCT05203939	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
NCT05906953	PHASE1/PHASE2	RECRUITING	Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
NCT06088992	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02575430	Not specified	COMPLETED	Natural History Study in Inherited Retinal Disease Subjects Caused by Mutations in RPE65 or LRAT
NCT02714816	Not specified	COMPLETED	Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65
NCT02946879	Not specified	COMPLETED	Long-Term Follow-Up Gene Therapy Study for Leber Congenital Amaurosis OPTIRPE65 (Retinal Dystrophy Associated With Defects in RPE65)
NCT02970266	Not specified	COMPLETED	Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families.
NCT07026565	Not specified	NOT_YET_RECRUITING	Psychotherapy Group for Parents of Children With LCA
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study