PDE6B

Summary

PDE6B (phosphodiesterase 6B, HGNC:8786) is a protein-coding gene on chromosome 4p16.3, encoding Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta (P35913). Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.

Photon absorption triggers a signaling cascade in rod photoreceptors that activates cGMP phosphodiesterase (PDE), resulting in the rapid hydrolysis of cGMP, closure of cGMP-gated cation channels, and hyperpolarization of the cell. PDE is a peripheral membrane heterotrimeric enzyme made up of alpha, beta, and gamma subunits. This gene encodes the beta subunit. Mutations in this gene result in retinitis pigmentosa and autosomal dominant congenital stationary night blindness. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5158 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 1,287 total — 102 pathogenic, 59 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8786
Approved symbol	PDE6B
Name	phosphodiesterase 6B
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	CSNB3, rd1, RP40, CSNBAD2
Ensembl gene	ENSG00000133256
Ensembl biotype	protein_coding
OMIM	180072
Entrez	5158

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 4 retained_intron

ENST00000255622, ENST00000429163, ENST00000460119, ENST00000461490, ENST00000465426, ENST00000467152, ENST00000471824, ENST00000474251, ENST00000476034, ENST00000487902, ENST00000488061, ENST00000496514

RefSeq mRNA: 7 — MANE Select: NM_000283 NM_000283, NM_001145291, NM_001145292, NM_001350154, NM_001350155, NM_001379246, NM_001379247

CCDS: CCDS33932, CCDS46993, CCDS54703

Canonical transcript exons

ENST00000496514 — 22 exons

Exon	Start	End
ENSE00000910138	663770	663870
ENSE00000910141	665255	665329
ENSE00001166447	635880	635969
ENSE00001166453	634677	634829
ENSE00001166491	654824	654888
ENSE00001201333	664114	664221
ENSE00001201345	663100	663187
ENSE00001201353	662509	662618
ENSE00001201366	660467	660613
ENSE00001201373	658952	659017
ENSE00001201381	657351	657494
ENSE00001201388	656874	657023
ENSE00001201399	655940	656006
ENSE00001201408	654080	654154
ENSE00001506937	667856	668006
ENSE00001506939	666531	666614
ENSE00001627935	662134	662241
ENSE00001654232	664881	664944
ENSE00001660130	656245	656292
ENSE00001840135	670046	670782
ENSE00001928019	625573	626094
ENSE00003650999	653852	653992

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 93.17.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8924 / max 204.0347, expressed in 813 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46503	1.7066	783
46500	0.5264	70
46497	0.3546	88
46498	0.1558	19
46501	0.1312	53
46499	0.0178	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	93.17	gold quality
right uterine tube	UBERON:0001302	89.43	gold quality
spinal cord	UBERON:0002240	88.66	gold quality
right frontal lobe	UBERON:0002810	86.99	gold quality
nucleus accumbens	UBERON:0001882	85.81	gold quality
caudate nucleus	UBERON:0001873	85.80	gold quality
putamen	UBERON:0001874	85.29	gold quality
amygdala	UBERON:0001876	84.61	gold quality
granulocyte	CL:0000094	84.39	gold quality
left lobe of thyroid gland	UBERON:0001120	83.81	gold quality
right lobe of thyroid gland	UBERON:0001119	83.76	gold quality
ventricular zone	UBERON:0003053	83.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.39	gold quality
corpus callosum	UBERON:0002336	82.24	gold quality
cingulate cortex	UBERON:0003027	82.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.02	gold quality
thyroid gland	UBERON:0002046	81.94	gold quality
anterior cingulate cortex	UBERON:0009835	81.90	gold quality
adenohypophysis	UBERON:0002196	81.39	gold quality
cortical plate	UBERON:0005343	81.31	gold quality
ganglionic eminence	UBERON:0004023	81.12	gold quality
spleen	UBERON:0002106	80.67	gold quality
hypothalamus	UBERON:0001898	80.38	gold quality
pituitary gland	UBERON:0000007	80.33	gold quality
prefrontal cortex	UBERON:0000451	80.01	gold quality
middle frontal gyrus	UBERON:0002702	79.73	gold quality
adrenal tissue	UBERON:0018303	78.86	gold quality
metanephros cortex	UBERON:0010533	78.24	gold quality
islet of Langerhans	UBERON:0000006	77.85	gold quality
apex of heart	UBERON:0002098	77.72	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	1872.47
E-MTAB-7316	yes	28.79
E-GEOD-137537	yes	21.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, FIZ1, NRL, SP1, SP4

miRNA regulators (miRDB)

37 targeting PDE6B, 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-6748-5P	100.00	65.81	1057
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
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-1250-3P	99.96	70.04	4038
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-1910-3P	98.44	67.51	1695

Literature-anchored findings (GeneRIF, showing 26)

• Sp4 is a strong activator of transcription from the beta-PDE promoter (PMID:11943774)
• the rod cGMP-phosphodiesterase beta-subunit gene is transcriptionally and post-transcriptionally regulated [review] (PMID:17249578)
• Clinical and genetic characterization of a Chinese family with PDE6B is reported. (PMID:18188951)
• PDE6B genes and the phenotypic heterogeneity and particularly the severe ocular affection first observed in one Usher syndrome patient. (PMID:18854872)
• These studies indicate that the 3’ UTR of the PDEbeta mRNA is involved in the complex regulation of this gene’s expression in the retina. (PMID:19218616)
• Rod phosphodiesterase-6 PDE6A and PDE6B subunits are enzymatically equivalent. (PMID:20940301)
• Mutations have been identified in the beta-subunit of rod phosphodiesterase in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa. (PMID:21655355)
• Data indicate the upregulation of RREB1, PDE6B, and CD209 suggests that these proteins might play important roles in the differentiation of primitive gut tube cells from embryonic stem cells (hESCs) and in primitive gut tube development into pancreas. (PMID:21792086)
• analysis of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6 (PMID:23033484)
• The p.H557Y mutation in PDE6B, was homozygous in four patients and heterozygous in nine patients, and it was the most frequent mutation (2.5%) in Korean patients with retinitis pigmentosa. (PMID:23049240)
• The family was found to segregate novel mutations of two different genes: myosin VIIA (MYO7A), and phosphodiesterase 6B, which causes nonsyndromic retinitis pigmentosa. (PMID:23882135)
• Next-generation whole exome sequencing revealed a homozygous c.1923_1969ins6del47 nonsense PDE6B mutation, which has not been previously described, that segregated with the disease in the family. (PMID:24828262)
• Heterozygous mutation in the PDE6B gene can cause a reduction in the rod function to different degrees. (PMID:25827439)
• A novel PDE6B founder variant is likely to account for 16% of recessive inherited retinal dystrophy in Maori. Careful characterization of the clinical presentation permits identification of further Maori patients with a similar phenotype and simplifies the diagnostic algorithm. (PMID:28488341)
• Mutation in PDE6B gene is associated with autosomal recessive retinitis pigmentosa disease progression. (PMID:30153077)
• A novel intronic mutation of PDE6B is a major cause of autosomal recessive retinitis pigmentosa among Caucasus Jews. (PMID:30820151)
• Mutations in PDE6A and PDE6B accounted for 1.6% and 2.4%, respectively, in a cohort of French patients with rod-cone dystrophy (RCD) (PMID:30998820)
• Clinical characteristics and disease progression of retinitis pigmentosa associated with PDE6B mutations in Korean patients. (PMID:33177553)
• Clinical and genetic investigations of three Moroccan families with retinitis pigmentosa phenotypes. (PMID:33633436)
• Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa. (PMID:33673512)
• Photoreceptor Phosphodiesterase (PDE6): Structure, Regulatory Mechanisms, and Implications for Treatment of Retinal Diseases. (PMID:34170501)
• PDE6B Mutation-associated Inherited Retinal Disease. (PMID:34584050)
• Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families. (PMID:35033039)
• Identification of a novel large multigene deletion and a frameshift indel in PDE6B as the underlying cause of early-onset recessive rod-cone degeneration. (PMID:36376065)
• A novel homozygous missense substitution p.Thr313Ile in the PDE6B gene underlies autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family. (PMID:36959549)
• A Novel Intronic Deletion in PDE6B Causes Autosomal Recessive Retinitis Pigmentosa by Interfering with RNA Splicing. (PMID:37094557)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde6a	ENSDARG00000000380
danio_rerio	pde6b	ENSDARG00000011671
mus_musculus	Pde6b	ENSMUSG00000029491
rattus_norvegicus	Pde6b	ENSRNOG00000000065
drosophila_melanogaster	Pde11	FBGN0085370
drosophila_melanogaster	Pde8	FBGN0266377
caenorhabditis_elegans		WBGENE00008443
caenorhabditis_elegans	pde-6	WBGENE00022389

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE6C (ENSG00000095464), PDE4C (ENSG00000105650), PDE10A (ENSG00000112541), PDE8B (ENSG00000113231), PDE4D (ENSG00000113448), PDE1A (ENSG00000115252), PDE1B (ENSG00000123360), PDE11A (ENSG00000128655), PDE6A (ENSG00000132915), PDE5A (ENSG00000138735), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta — P35913 (reviewed: P35913)

All UniProt accessions (5): C9J628, C9J7V6, P35913, H7C4F7, H7C4P9

UniProt curated annotations — full annotation on UniProt →

Function. Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP. Necessary for the formation of a functional phosphodiesterase holoenzyme. Involved in retinal circadian rhythm photoentrainment via modulation of UVA and orange light-induced phase-shift of the retina clock. May participate in processes of transmission and amplification of the visual signal.

Subunit / interactions. Oligomer composed of two catalytic chains (alpha and beta), an inhibitory chain (gamma) and the delta chain.

Subcellular location. Membrane. Cell projection. Cilium. Photoreceptor outer segment.

Disease relevance. Retinitis pigmentosa 40 (RP40) [MIM:613801] 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. Night blindness, congenital stationary, autosomal dominant 2 (CSNBAD2) [MIM:163500] A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.

Similarity. Belongs to the cyclic nucleotide phosphodiesterase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P35913-1	1	yes
P35913-2	2
P35913-3	3

RefSeq proteins (7): NP_000274, NP_001138763, NP_001138764, NP_001337083, NP_001337084, NP_001366175, NP_001366176 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002073	PDEase_catalytic_dom	Domain
IPR003018	GAF	Domain
IPR003607	HD/PDEase_dom	Domain
IPR023088	PDEase	Family
IPR023174	PDEase_CS	Conserved_site
IPR029016	GAF-like_dom_sf	Homologous_superfamily
IPR036971	PDEase_catalytic_dom_sf	Homologous_superfamily

Pfam: PF00233, PF01590

Catalyzed reactions (Rhea), 1 shown:

• 3’,5’-cyclic GMP + H2O = GMP + H(+) (RHEA:16957)

UniProt features (39 total): sequence variant 18, binding site 5, sequence conflict 5, domain 3, splice variant 2, initiator methionine 1, chain 1, modified residue 1, lipid moiety-binding region 1, propeptide 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35913-F1	89.72	0.73

Functional residue map

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

Catalytic / active sites (1): 557 (proton donor)

Ligand- & substrate-binding residues (5): 598; 718; 561; 597; 598

Post-translational modifications (2): 2, 851

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2485179	Activation of the phototransduction cascade
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-4086398	Ca2+ pathway

MSigDB gene sets: 190 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_PHOTOPERIODISM, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_PHOTOTRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GCM_PRKCG, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GCM_RING1, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, TGCTGAY_UNKNOWN, GCM_FCGR2B, MARTIN_VIRAL_GPCR_SIGNALING_UP, GOBP_RESPONSE_TO_RADIATION

GO Biological Process (8): visual perception (GO:0007601), phototransduction, visible light (GO:0007603), entrainment of circadian clock by photoperiod (GO:0043153), retina development in camera-type eye (GO:0060041), negative regulation of cAMP/PKA signal transduction (GO:0141162), retinal cell apoptotic process (GO:1990009), signal transduction (GO:0007165), detection of light stimulus (GO:0009583)

GO Molecular Function (7): 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (6): plasma membrane (GO:0005886), photoreceptor outer segment membrane (GO:0042622), photoreceptor disc membrane (GO:0097381), photoreceptor outer segment (GO:0001750), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
The phototransduction cascade	2
Beta-catenin independent WNT signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
photoreceptor outer segment	2
sensory perception of light stimulus	1
phototransduction	1
detection of visible light	1
photoperiodism	1
entrainment of circadian clock	1
camera-type eye development	1
anatomical structure development	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
apoptotic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to light stimulus	1
detection of external stimulus	1
detection of abiotic stimulus	1
cation binding	1
cyclic-nucleotide phosphodiesterase activity	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
membrane	1
cell periphery	1
ciliary membrane	1
organelle membrane	1
photoreceptor cell cilium	1

Protein interactions and networks

STRING

1360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE6B	PRPH2	P23942	968
PDE6B	PDE6G	P18545	949
PDE6B	RD3	Q7Z3Z2	913
PDE6B	RHO	P08100	870
PDE6B	ESX1	Q8N693	869
PDE6B	CNGA1	P29973	855
PDE6B	RPE65	Q16518	842
PDE6B	CRX	O43186	837
PDE6B	NXNL1	Q96CM4	832
PDE6B	PDE6A	P16499	831
PDE6B	GUCA1B	Q9UMX6	830
PDE6B	GNAT1	P11488	829
PDE6B	CNGB1	Q14028	808
PDE6B	FAM161A	Q3B820	788
PDE6B	RPGR	Q92834	788

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CLOCK	BMAL1	psi-mi:“MI:0914”(association)	0.880
PDE6B	PYGB	psi-mi:“MI:0914”(association)	0.350
RBM10	RPS3	psi-mi:“MI:0914”(association)	0.350
PIWIL1	PDE6B	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): MUL1 (Affinity Capture-MS), FEM1B (Affinity Capture-MS), PDE6B (Affinity Capture-MS), PDE6B (Affinity Capture-MS), PYGB (Affinity Capture-MS), PDE6B (Affinity Capture-MS), PDE6B (Affinity Capture-MS), PDE6B (Affinity Capture-MS), PDE6B (Affinity Capture-Western)

ESM2 similar proteins: B3LVW5, B3P3K2, B4G4E5, B4HEM4, B4JXX2, B4K9L4, B4LVU6, B4NAL6, B4PSS5, B4QZU1, E9Q4S1, O18696, O18965, O54735, O60658, O76074, O77746, O88502, O95259, O95263, P0C1Q2, P11541, P16499, P16586, P23439, P23440, P27664, P33726, P35913, P51160, P52731, P91119, Q01062, Q02280, Q07093, Q1KKS3, Q28156, Q28263, Q298P4, Q60603

Diamond homologs: B3LVW5, B3P3K2, B4G4E5, B4HEM4, B4JXX2, B4K9L4, B4LVU6, B4NAL6, B4PSS5, B4QZU1, B7YZV4, H2QL32, O00408, O54735, O70628, O76074, O76083, O77746, O89084, P0C1Q2, P11541, P14099, P14100, P14644, P14646, P16499, P16586, P23439, P23440, P27664, P27815, P30645, P33726, P35913, P51160, P52731, P54748, P54750, P91119, Q01061

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1287 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	102
Likely pathogenic	59
Uncertain significance	580
Likely benign	348
Benign	55

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1051624	NM_000283.4(PDE6B):c.1370A>G (p.Lys457Arg)	Pathogenic
1066621	NM_000283.4(PDE6B):c.992+1G>C	Pathogenic
1068671	NM_000283.4(PDE6B):c.2419T>C (p.Trp807Arg)	Pathogenic
1068923	NM_000283.4(PDE6B):c.2038C>T (p.Gln680Ter)	Pathogenic
1069615	NM_000283.4(PDE6B):c.25del (p.Arg9fs)	Pathogenic
1070608	NC_000004.11:g.(?647641)(648677_?)del	Pathogenic
1074503	NM_000283.4(PDE6B):c.756del (p.Asp252fs)	Pathogenic
1076460	NC_000004.11:g.(?652721)(656427_?)del	Pathogenic
1184486	NM_000283.4(PDE6B):c.853-1G>A	Pathogenic
1184487	NM_000283.4(PDE6B):c.1160C>T (p.Pro387Leu)	Pathogenic
1213876	NM_000283.4(PDE6B):c.510C>G (p.Tyr170Ter)	Pathogenic
13103	NM_000283.4(PDE6B):c.892C>T (p.Gln298Ter)	Pathogenic
13104	NM_000283.4(PDE6B):c.1591C>T (p.Arg531Ter)	Pathogenic
13105	NM_000283.4(PDE6B):c.1488del (p.Thr497fs)	Pathogenic
13106	NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr)	Pathogenic
13108	NM_000283.4(PDE6B):c.169_239dup (p.Leu83fs)	Pathogenic
13109	NM_000283.4(PDE6B):c.2419T>A (p.Trp807Arg)	Pathogenic
1333030	NM_000283.4(PDE6B):c.863_864del (p.Asp288fs)	Pathogenic
1358080	NM_000283.4(PDE6B):c.262C>T (p.Gln88Ter)	Pathogenic
1370592	NM_000283.4(PDE6B):c.1134G>A (p.Trp378Ter)	Pathogenic
1371337	NM_000283.4(PDE6B):c.80_81del (p.Leu27fs)	Pathogenic
1385018	NM_000283.4(PDE6B):c.1765dup (p.Ala589fs)	Pathogenic
1413600	NM_000283.4(PDE6B):c.2257C>T (p.Gln753Ter)	Pathogenic
143065	NM_000283.4(PDE6B):c.1467+1G>C	Pathogenic
143067	NM_000283.4(PDE6B):c.1604T>A (p.Ile535Asn)	Pathogenic
1440695	NM_000283.4(PDE6B):c.1281G>A (p.Trp427Ter)	Pathogenic
1444787	NM_000283.4(PDE6B):c.703_704insT (p.Arg235fs)	Pathogenic
1451206	NM_000283.4(PDE6B):c.1615-1G>C	Pathogenic
1456396	NM_000283.4(PDE6B):c.1488dup (p.Thr497fs)	Pathogenic
1456526	NM_000283.4(PDE6B):c.2455A>T (p.Lys819Ter)	Pathogenic

SpliceAI

4309 predictions. Top by Δscore:

Variant	Effect	Δscore
4:626083:G:GT	donor_gain	1.0000
4:626091:CGAGG:C	donor_loss	1.0000
4:626093:AGGT:A	donor_loss	1.0000
4:626094:GGT:G	donor_loss	1.0000
4:634671:C:CA	acceptor_gain	1.0000
4:634826:AGAT:A	donor_gain	1.0000
4:634827:GAT:G	donor_gain	1.0000
4:634827:GATG:G	donor_gain	1.0000
4:634827:GATGT:G	donor_loss	1.0000
4:634828:AT:A	donor_gain	1.0000
4:634829:TG:T	donor_loss	1.0000
4:634830:G:GG	donor_gain	1.0000
4:635872:T:A	acceptor_gain	1.0000
4:635875:TTCA:T	acceptor_loss	1.0000
4:635878:A:AT	acceptor_loss	1.0000
4:635879:GGT:G	acceptor_gain	1.0000
4:653847:TCCA:T	acceptor_loss	1.0000
4:653848:CCAG:C	acceptor_loss	1.0000
4:653849:CAGG:C	acceptor_loss	1.0000
4:653850:A:AG	acceptor_gain	1.0000
4:653850:AG:A	acceptor_gain	1.0000
4:653851:G:GA	acceptor_gain	1.0000
4:653851:GG:G	acceptor_gain	1.0000
4:653851:GGT:G	acceptor_gain	1.0000
4:653989:GAAG:G	donor_gain	1.0000
4:653993:G:GA	donor_loss	1.0000
4:653993:G:GG	donor_gain	1.0000
4:654150:GCCGG:G	donor_gain	1.0000
4:654151:CCGGG:C	donor_loss	1.0000
4:654152:CGGGT:C	donor_loss	1.0000

AlphaMissense

5716 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:662188:C:A	H557N	1.000
4:662188:C:G	H557D	1.000
4:662188:C:T	H557Y	1.000
4:662189:A:T	H557L	1.000
4:662190:C:A	H557Q	1.000
4:662190:C:G	H557Q	1.000
4:662200:C:G	H561D	1.000
4:662575:C:G	H597D	1.000
4:662578:G:A	D598N	1.000
4:662578:G:C	D598H	1.000
4:662579:A:C	D598A	1.000
4:662579:A:G	D598G	1.000
4:662579:A:T	D598V	1.000
4:662580:C:A	D598E	1.000
4:662580:C:G	D598E	1.000
4:662587:C:G	H601D	1.000
4:662589:C:A	H601Q	1.000
4:662589:C:G	H601Q	1.000
4:662591:G:C	R602P	1.000
4:662593:G:C	G603R	1.000
4:662594:G:A	G603D	1.000
4:662594:G:T	G603V	1.000
4:662601:C:A	N605K	1.000
4:662601:C:G	N605K	1.000
4:662604:C:A	N606K	1.000
4:662604:C:G	N606K	1.000
4:663143:G:A	E626K	1.000
4:663144:A:T	E626V	1.000
4:663145:G:C	E626D	1.000
4:663145:G:T	E626D	1.000

dbSNP variants (sampled 300 via entrez): RS1000056791 (4:643135 C>T), RS1000137871 (4:650435 C>T), RS10001451 (4:631902 A>G,T), RS1000166867 (4:645326 C>A,T), RS1000179415 (4:667810 A>G), RS1000247905 (4:645481 G>A,C), RS10002807 (4:633315 C>A,T), RS1000322253 (4:663730 G>A), RS1000383935 (4:630092 C>A), RS1000501557 (4:634145 C>A), RS1000514139 (4:666701 A>G,T), RS1000644969 (4:628998 G>A), RS1000664281 (4:640351 G>A), RS1000678779 (4:640540 G>A), RS1000697415 (4:629245 C>T)

Disease associations

OMIM: gene MIM:180072 | disease phenotypes: MIM:163500, MIM:268000, MIM:613801, MIM:616917, MIM:204000, MIM:203200, MIM:310500, MIM:120970

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 40	Definitive	Autosomal recessive
congenital stationary night blindness autosomal dominant 2	Strong	Autosomal dominant
congenital stationary night blindness	Supportive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AR

Mondo (10): inherited retinal dystrophy (MONDO:0019118), congenital stationary night blindness autosomal dominant 2 (MONDO:0008099), retinitis pigmentosa (MONDO:0019200), retinitis pigmentosa 40 (MONDO:0013429), prostate cancer (MONDO:0008315), intellectual disability, autosomal recessive 53 (MONDO:0014832), Leber congenital amaurosis (MONDO:0018998), oculocutaneous albinism type 2 (MONDO:0008746), congenital stationary night blindness (MONDO:0016293), cone-rod dystrophy (MONDO:0015993)

Orphanet (8): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Congenital stationary night blindness (Orphanet:215), Retinitis pigmentosa (Orphanet:791), Familial prostate cancer (Orphanet:1331), Early-onset epilepsy-intellectual disability-brain anomalies syndrome (Orphanet:488635), Leber congenital amaurosis (Orphanet:65), Oculocutaneous albinism type 2 (Orphanet:79432), Cone rod dystrophy (Orphanet:1872)

HPO phenotypes

40 total (30 of 40 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:0000518	Cataract
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001098	Abnormal fundus morphology
HP:0001105	Retinal atrophy
HP:0007642	Early-onset non-progressive night blindness
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss

GWAS associations

0 associations (top):

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
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
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C566869	Night Blindness, Congenital Stationary, Autosomal Dominant 2 (supp.)
C536122	Night blindness, congenital stationary (supp.)
C537730	Oculocutaneous albinism type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095220 (SELECTIVITY GROUP), CHEMBL2097163 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3430880 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 154,266 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1520	VARDENAFIL	4	21,078
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL779	TADALAFIL	4	23,417
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL28079	ZAPRINAST	2	16,158
CHEMBL3109802	TBA-7371	2	51

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Phosphodiesterases, 3’,5’-cyclic nucleotide (PDEs)

ChEMBL bioactivities

112 potent at pChembl≥5 of 120 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5081214
9.90	IC50	0.1259	nM	CHEMBL5080391
9.80	IC50	0.1585	nM	CHEMBL5087564
9.60	IC50	0.2512	nM	CHEMBL5094110
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.30	IC50	0.5	nM	SILDENAFIL
9.00	IC50	1	nM	VARDENAFIL
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742
8.66	IC50	2.2	nM	CHEMBL2414311
8.13	IC50	7.4	nM	CHEMBL2180942
8.02	IC50	9.5	nM	SILDENAFIL
7.96	IC50	11	nM	VARDENAFIL
7.60	IC50	25	nM	SILDENAFIL
7.52	IC50	30.1	nM	CHEMBL4062273
7.40	IC50	40	nM	SILDENAFIL
7.30	Ki	50	nM	SILDENAFIL
7.21	IC50	62	nM	CHEMBL213060
7.14	IC50	73.15	nM	CHEMBL2069321
6.90	Ki	125	nM	DIPYRIDAMOLE
6.90	IC50	125	nM	CHEMBL282515
6.75	IC50	180	nM	CHEMBL373102
6.68	Ki	211	nM	CHEMBL1939800
6.65	IC50	226	nM	CHEMBL284070
6.60	IC50	249	nM	CHEMBL32255
6.57	IC50	271	nM	CHEMBL33518
6.56	IC50	276	nM	CHEMBL2070655
6.56	Ki	278	nM	CHEMBL1939803
6.55	IC50	280	nM	CHEMBL212397
6.48	IC50	330	nM	CHEMBL377563
6.48	IC50	330	nM	CHEMBL378255
6.48	IC50	330	nM	CHEMBL5434573
6.47	IC50	339	nM	CHEMBL2333219
6.46	IC50	349	nM	CHEMBL2070649
6.45	IC50	357	nM	CHEMBL418594
6.45	IC50	358	nM	CHEMBL33121
6.40	Ki	400	nM	ZAPRINAST
6.36	IC50	435	nM	CHEMBL2070639
6.33	IC50	462	nM	CHEMBL2070631
6.31	IC50	493	nM	CHEMBL2070651
6.31	IC50	494	nM	CHEMBL282515
6.26	IC50	550	nM	CHEMBL213219
6.26	Ki	554	nM	CHEMBL1939802
6.25	IC50	561	nM	CHEMBL4554391
6.21	IC50	610	nM	CHEMBL438451
6.21	IC50	611	nM	CHEMBL5977186
6.21	IC50	620	nM	CHEMBL285737
6.16	IC50	693	nM	CHEMBL2070654
6.16	Ki	697	nM	CHEMBL1939804

PubChem BioAssay actives

102 with measured affinity, of 190 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]sulfamoyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[N-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxycarbonyl]anilino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0001	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0002	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]sulfamoyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
Sildenafil	735483: Inhibition of PDE6 (unknown origin) using FAM-cGMP as substrate after 60 mins by fluorescence assay	ic50	0.0005	uM
Vardenafil	240962: Inhibition of human phosphodiesterase 6	ic50	0.0010	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[N-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxycarbonyl]anilino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0010	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0010	uM
(2S)-1-[3-(5-bromo-6-oxo-4-propan-2-yl-1H-pyrimidin-2-yl)-4-propoxyphenyl]sulfonylpyrrolidine-2-carboxylic acid	764685: Inhibition of PDE6 (unknown origin)	ic50	0.0022	uM
5-bromo-2-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-4-propan-2-yl-1H-pyrimidin-6-one	764685: Inhibition of PDE6 (unknown origin)	ic50	0.0074	uM
2-acetyl-10-[(3-chloro-4-methoxyphenyl)methylamino]-3,4-dihydro-1H-benzo[b][1,6]naphthyridine-8-carbonitrile	1866074: Inhibition of PDE6 (unknown origin) using FAM-cGMP or FAM-cAMP as substrate incubated for 60 mins and measured by fluorescence polarization assay	ic50	0.0301	uM
11-benzyl-13-methyl-4-phenyl-7-propan-2-yl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.0620	uM
1-(2-chlorophenyl)-6,8-dimethoxy-3-methylimidazo[5,1-c][1,2,4]benzotriazine	678635: Inhibition of PDE6	ic50	0.0732	uM
Dipyridamole	238297: Inhibition of human phosphodiesterase 6	ki	0.1250	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[(3R)-1-[2-(1-methylimidazol-2-yl)ethyl]pyrrolidin-3-yl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.1250	uM
(7R)-7-benzyl-2-bromo-5-ethyl-3-[(4-hydroxyphenyl)methyl]-7,8-dihydroimidazo[2,1-b]purin-4-one	240962: Inhibition of human phosphodiesterase 6	ic50	0.1800	uM
6-methoxy-3,8-dimethyl-N-(pyridin-4-ylmethyl)-2H-pyrazolo[3,4-b]quinolin-4-amine	640658: Inhibition of recombinant human PDE6 using [3H]cAMP as substrate by scintillation proximity assay	ki	0.2110	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[(3R)-1-(2-pyridin-2-ylethyl)pyrrolidin-3-yl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.2260	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[(3R)-1-benzylpyrrolidin-3-yl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.2490	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[(3R)-1-(2-pyridin-3-ylethyl)pyrrolidin-3-yl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.2710	uM
4-[1-(2-chlorophenyl)-6-methoxy-3-methylimidazo[5,1-c][1,2,4]benzotriazin-8-yl]morpholine	678635: Inhibition of PDE6	ic50	0.2760	uM
6-methoxy-3,8-dimethyl-N-(oxan-4-yl)-2H-pyrazolo[3,4-b]quinolin-4-amine	640658: Inhibition of recombinant human PDE6 using [3H]cAMP as substrate by scintillation proximity assay	ki	0.2780	uM
11-benzyl-7,13-dimethyl-4-pyridin-3-yl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.2800	uM
11-benzyl-4-(furan-3-yl)-7,13-dimethyl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.3300	uM
11-benzyl-13-(ethoxymethyl)-7-methyl-4-phenyl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.3300	uM
N-(2-pyrazin-2-yl-4,6-dihydrothieno[3,4-c]pyrazol-3-yl)naphthalene-1-carboxamide	1994821: Inhibition of PDE (unknown origin)	ic50	0.3300	uM
4-[(3-chloro-4-methoxyphenyl)methylamino]-8-cyclopropyl-3-(hydroxymethyl)quinoline-6-carbonitrile	1866074: Inhibition of PDE6 (unknown origin) using FAM-cGMP or FAM-cAMP as substrate incubated for 60 mins and measured by fluorescence polarization assay	ic50	0.3390	uM
6,8-dimethoxy-3-methyl-1-(2-methylphenyl)imidazo[5,1-c][1,2,4]benzotriazine	678635: Inhibition of PDE6	ic50	0.3490	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[(3R)-1-[2-(1H-imidazol-2-yl)ethyl]pyrrolidin-3-yl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.3570	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[(3R)-1-(2-pyrazin-2-ylethyl)pyrrolidin-3-yl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.3580	uM
5-(2-propoxyphenyl)-2,6-dihydrotriazolo[4,5-d]pyrimidin-7-one	238389: Inhibition of human phosphodiesterase 6	ki	0.4000	uM
3-(2-chlorophenyl)-12-methoxy-5-methyl-2,4,7,8,13-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	678635: Inhibition of PDE6	ic50	0.4350	uM
3-(2-chloro-4-fluorophenyl)-12-methoxy-5-methyl-2,4,7,8,13-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	678635: Inhibition of PDE6	ic50	0.4620	uM
6,8-dimethoxy-3-methyl-1-(2-methyl-3-pyridinyl)imidazo[5,1-c][1,2,4]benzotriazine	678635: Inhibition of PDE6	ic50	0.4930	uM
11-benzyl-7-ethyl-13-methyl-4-phenyl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.5500	uM
6-methoxy-3,8-dimethyl-N-(2-pyridin-4-ylethyl)-2H-pyrazolo[3,4-b]quinolin-4-amine	640658: Inhibition of recombinant human PDE6 using [3H]cAMP as substrate by scintillation proximity assay	ki	0.5540	uM
1-[[2-(7-fluoro-3-methylquinoxalin-2-yl)-5-[(3R)-3-fluoropyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-7-yl]amino]-2-methylpropan-2-ol;hydrochloride	1552322: Inhibition of PDE6 (unknown origin)	ic50	0.5610	uM
11-benzyl-13-methyl-4-phenyl-7-propyl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.6100	uM
3-[(3R)-3-[(2R,8R)-2-(1,3-benzodioxol-5-yl)-4,7-dioxo-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-6-yl]pyrrolidin-1-yl]-N-ethylpropanamide	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.6200	uM
4-[6-methoxy-3-methyl-1-(2-methylphenyl)imidazo[5,1-c][1,2,4]benzotriazin-8-yl]morpholine	678635: Inhibition of PDE6	ic50	0.6930	uM
6-methoxy-3,8-dimethyl-N-(oxan-4-ylmethyl)-2H-pyrazolo[3,4-b]quinolin-4-amine	640658: Inhibition of recombinant human PDE6 using [3H]cAMP as substrate by scintillation proximity assay	ki	0.6970	uM
3-(2-fluoro-5-methoxyphenyl)-12-methoxy-5-methyl-2,4,7,8,13-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	678635: Inhibition of PDE6	ic50	0.7340	uM
3-[(3R)-3-[(2R,8R)-2-(1,3-benzodioxol-5-yl)-4,7-dioxo-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-6-yl]pyrrolidin-1-yl]-N,N-dimethylpropanamide	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.8070	uM
3-(2,5-dichlorophenyl)-12-methoxy-5-methyl-2,4,7,8,13-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	678635: Inhibition of PDE6	ic50	0.8290	uM
6-methoxy-3,8-dimethyl-N-(oxan-2-ylmethyl)-2H-pyrazolo[3,4-b]quinolin-4-amine	640658: Inhibition of recombinant human PDE6 using [3H]cAMP as substrate by scintillation proximity assay	ki	0.8430	uM
(2R,8R)-6-[(3R)-1-[3-(azetidin-1-yl)-3-oxopropyl]pyrrolidin-3-yl]-2-(1,3-benzodioxol-5-yl)-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	158129: Inhibitory activity against phosphodiesterase 6 (PDE6) obtained from canine or bovine retina	ic50	0.8460	uM
11-benzyl-13-methyl-4-phenyl-5,6,8,11,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4,7,12-pentaen-10-one	269694: Inhibition of PDE6	ic50	0.8600	uM
8-(difluoromethoxy)-6-methoxy-3-methyl-1-(3-methyl-4-pyridinyl)imidazo[5,1-c][1,2,4]benzotriazine	678635: Inhibition of PDE6	ic50	0.9090	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Lead	increases expression	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

57 unique, capped per target: 54 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL832228	Binding	Relative binding to Phosphodiesterase 6 and Phosphodiesterase 5, ratio of IC50	Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED. — Bioorg Med Chem Lett
CHEMBL4348841	ADMET	Inhibition of PDE6 (unknown origin)	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability. — J Med Chem

Clinical trials (associated diseases)

259 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)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
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