PDE6H

Summary

PDE6H (phosphodiesterase 6H, HGNC:8790) is a protein-coding gene on chromosome 12p12.3, encoding Retinal cone rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit gamma (Q13956). Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.

This gene encodes the inhibitory (or gamma) subunit of the cone-specific cGMP phosphodiesterase, which is a tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma). It is specifically expressed in the retina, and is involved in the transmission and amplification of the visual signal. Mutations in this gene are associated with retinal cone dystrophy type 3A (RCD3A).

Source: NCBI Gene 5149 — RefSeq curated summary.

At a glance

• Gene–disease (curated): achromatopsia 6 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 70 total
• Phenotypes (HPO): 29
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8790
Approved symbol	PDE6H
Name	phosphodiesterase 6H
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139053
Ensembl biotype	protein_coding
OMIM	601190
Entrez	5149

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000266395, ENST00000945511

RefSeq mRNA: 1 — MANE Select: NM_006205 NM_006205

CCDS: CCDS8672

Canonical transcript exons

ENST00000266395 — 4 exons

Exon	Start	End
ENSE00000936293	14977972	14978146
ENSE00000936294	14979179	14979219
ENSE00000999869	14973042	14973086
ENSE00001158782	14981400	14981865

Expression profiles

Bgee: expression breadth broad, 83 present calls, max score 92.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.7125 / max 2590.9295, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124473	2.7125	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.72	gold quality
monocyte	CL:0000576	66.62	gold quality
mononuclear cell	CL:0000842	66.46	gold quality
leukocyte	CL:0000738	64.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.32	gold quality
granulocyte	CL:0000094	63.42	gold quality
bone marrow cell	CL:0002092	62.65	gold quality
retina	UBERON:0000966	59.21	silver quality
pigmented layer of retina	UBERON:0001782	59.21	gold quality
right frontal lobe	UBERON:0002810	59.04	gold quality
prefrontal cortex	UBERON:0000451	58.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.70	gold quality
paraflocculus	UBERON:0005351	55.46	gold quality
frontal cortex	UBERON:0001870	55.33	gold quality
choroid plexus epithelium	UBERON:0003911	55.22	silver quality
cingulate cortex	UBERON:0003027	54.94	gold quality
anterior cingulate cortex	UBERON:0009835	54.68	gold quality
bone marrow	UBERON:0002371	54.59	gold quality
neocortex	UBERON:0001950	54.44	gold quality
right adrenal gland cortex	UBERON:0035827	52.72	gold quality
hypothalamus	UBERON:0001898	52.64	gold quality
cerebral cortex	UBERON:0000956	52.17	gold quality
blood	UBERON:0000178	51.36	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
telencephalon	UBERON:0001893	50.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
substantia nigra	UBERON:0002038	49.68	gold quality
quadriceps femoris	UBERON:0001377	49.58	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	25714.69
E-MTAB-11121	yes	10104.25
E-GEOD-137537	yes	6235.65
E-GEOD-98556	yes	1145.97
E-ANND-3	no	1.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting PDE6H, 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-548P	99.98	72.25	3784
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-934	98.49	70.44	581
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-4680-5P	96.43	67.15	893
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-8083	95.93	67.55	694
HSA-MIR-4693-3P	95.23	65.92	735

Literature-anchored findings (GeneRIF, showing 2)

• Our results indicate that mutations in the PDE6H gene are not common, because only 1 of 240 patients with cone dystrophy showed a single nucleotide substitution in the 5’ UTR of PDE6H mRNA (PMID:15629837)
• These findings add PDE6H to the set of genes involved in autosomal-recessive cone disorders and demonstrate the importance of the inhibitory gamma subunit in cone phototransduction (PMID:22901948)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pde6h	ENSMUSG00000064330
rattus_norvegicus	Pde6h	ENSRNOG00000005947

Paralogs (1): PDE6G (ENSG00000185527)

Protein

Protein identifiers

Retinal cone rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit gamma — Q13956 (reviewed: Q13956)

All UniProt accessions (1): Q13956

UniProt curated annotations — full annotation on UniProt →

Function. Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.

Subunit / interactions. Tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma).

Disease relevance. Achromatopsia 6 (ACHM6) [MIM:610024] An autosomal recessive form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by colorblindness, low visual acuity, photophobia and nystagmus. ACHM6 patients have incomplete loss of color vision, and non-progressive reduced visual acuity. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal region is important in conferring inhibition.

Similarity. Belongs to the rod/cone cGMP-PDE gamma subunit family.

RefSeq proteins (1): NP_006196* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006952	PDE6_gamma	Family
IPR037030	PDE6_gamma_sf	Homologous_superfamily

Pfam: PF04868

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (4 total): compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13956-F1	67.61	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, RACCACAR_AML_Q6, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, PID_CONE_PATHWAY, GOBP_ERBB_SIGNALING_PATHWAY, MORF_CTSB, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, TGANTCA_AP1_C, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MODULE_497, KEGG_PURINE_METABOLISM, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, AML1_01

GO Biological Process (4): visual perception (GO:0007601), positive regulation of MAPK cascade (GO:0043410), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), positive regulation of G protein-coupled receptor signaling pathway (GO:0045745)

GO Molecular Function (6): enzyme inhibitor activity (GO:0004857), cGMP binding (GO:0030553), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): photoreceptor outer segment membrane (GO:0042622)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
sensory perception of light stimulus	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
G protein-coupled receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
positive regulation of signal transduction	1
enzyme regulator activity	1
molecular function inhibitor activity	1
cyclic nucleotide binding	1
guanyl ribonucleotide binding	1
anion binding	1
3’,5’-cyclic-nucleotide phosphodiesterase activity	1
cyclic-nucleotide phosphodiesterase activity	1
binding	1
photoreceptor outer segment	1
ciliary membrane	1

Protein interactions and networks

STRING

839 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE6H	KCNV2	Q8TDN2	977
PDE6H	PDE6C	P51160	916
PDE6H	GNAT2	P19087	881
PDE6H	CNGB3	Q9NQW8	855
PDE6H	CNGA3	Q16281	826
PDE6H	PDE6A	P16499	741
PDE6H	ARR3	P36575	702
PDE6H	ALDH7A1	P49419	700
PDE6H	CNGA1	P29973	675
PDE6H	GNGT2	O14610	649
PDE6H	PDE6B	P35913	632
PDE6H	GNAT1	P11488	621
PDE6H	CRX	O43186	616
PDE6H	GNGT1	P63211	609
PDE6H	OPN1SW	P03999	609

IntAct

25 interactions, top by confidence:

A	B	Type	Score
COTL1	PDE6H	psi-mi:“MI:0915”(physical association)	0.560
AGTR1	PDE6H	psi-mi:“MI:0915”(physical association)	0.560
PDE6H	COTL1	psi-mi:“MI:0915”(physical association)	0.560
PDE6H	AGTR1	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	PDE6H	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	PDE6H	psi-mi:“MI:0915”(physical association)	0.560
PDE6H	CHAT	psi-mi:“MI:0915”(physical association)	0.560
PDE6H	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
PDE6H	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
PDE6H	H1-3	psi-mi:“MI:0915”(physical association)	0.400
PDE6H	FLAD1	psi-mi:“MI:0915”(physical association)	0.400
CRY1	IGKV2D-30	psi-mi:“MI:0914”(association)	0.350
PDE6H	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
PRKAB2	PDE6H	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): PDE6H (Two-hybrid), COTL1 (Two-hybrid), PDE6H (Affinity Capture-MS), PDE6H (Two-hybrid), PDE6H (Two-hybrid), PDE6H (Proximity Label-MS), FLAD1 (Affinity Capture-MS), PDE6H (Affinity Capture-MS), PDE6H (Affinity Capture-MS), PDE6H (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: B0G125, C0HJX9, O31159, O36424, O41801, O60356, O75956, P04972, P09174, P0C1J9, P0C6L6, P0C7T1, P0DM49, P0DM50, P0DM70, P0DSF3, P0DV82, P11207, P12506, P14478, P17285, P18545, P19589, P19815, P22571, P29137, P30927, P30928, P33483, P54827, P60167, P61248, P61249, P61250, P82657, P83688, P84563, P85214, P85517, Q13956

Diamond homologs: O55175, P04972, P09174, P18545, P22571, P54827, P61248, P61249, P61250, Q13956, Q9EQQ8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	22
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

602 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14977962:A:AG	acceptor_gain	1.0000
12:14979176:T:G	acceptor_gain	1.0000
12:14979177:A:AG	acceptor_gain	1.0000
12:14979178:G:GG	acceptor_gain	1.0000
12:14973082:GCTCC:G	donor_gain	0.9900
12:14973087:G:GG	donor_gain	0.9900
12:14977962:ACT:A	acceptor_gain	0.9900
12:14977963:C:G	acceptor_gain	0.9900
12:14977964:T:A	acceptor_gain	0.9900
12:14977969:AAG:A	acceptor_gain	0.9900
12:14977970:A:G	acceptor_gain	0.9900
12:14978145:GG:G	donor_gain	0.9900
12:14978146:GG:G	donor_gain	0.9900
12:14979173:CCATA:C	acceptor_loss	0.9900
12:14979174:CATAG:C	acceptor_loss	0.9900
12:14979175:ATAG:A	acceptor_loss	0.9900
12:14979176:TA:T	acceptor_loss	0.9900
12:14979177:A:G	acceptor_loss	0.9900
12:14979178:G:A	acceptor_loss	0.9900
12:14979178:GATTT:G	acceptor_gain	0.9900
12:14979218:AG:A	donor_loss	0.9900
12:14979219:GGTAA:G	donor_loss	0.9900
12:14979221:TAAG:T	donor_loss	0.9900
12:14973083:CTCC:C	donor_gain	0.9800
12:14973084:TCC:T	donor_gain	0.9800
12:14973085:CC:C	donor_gain	0.9800
12:14973086:CG:C	donor_loss	0.9800
12:14980686:G:GT	donor_gain	0.9800
12:14980727:AAGAG:A	donor_gain	0.9800
12:14973088:TGAG:T	donor_loss	0.9700

AlphaMissense

543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14978112:T:C	F34L	1.000
12:14978114:C:A	F34L	1.000
12:14978114:C:G	F34L	1.000
12:14981420:T:A	W66R	1.000
12:14981420:T:C	W66R	1.000
12:14981422:G:C	W66C	1.000
12:14981422:G:T	W66C	1.000
12:14981465:G:T	G81W	1.000
12:14978113:T:C	F34S	0.999
12:14978113:T:G	F34C	0.999
12:14978115:A:G	K35E	0.999
12:14978117:G:C	K35N	0.999
12:14978117:G:T	K35N	0.999
12:14981414:T:A	C64S	0.999
12:14981414:T:C	C64R	0.999
12:14981415:G:A	C64Y	0.999
12:14981415:G:C	C64S	0.999
12:14981416:T:G	C64W	0.999
12:14981421:G:C	W66S	0.999
12:14981429:T:C	F69L	0.999
12:14981431:C:A	F69L	0.999
12:14981431:C:G	F69L	0.999
12:14981445:T:C	L74S	0.999
12:14981454:T:A	L77H	0.999
12:14981454:T:C	L77P	0.999
12:14981465:G:A	G81R	0.999
12:14981465:G:C	G81R	0.999
12:14981466:G:A	G81E	0.999
12:14981466:G:T	G81V	0.999
12:14978088:T:C	F26L	0.998

dbSNP variants (sampled 300 via entrez): RS1000393023 (12:14973503 A>G), RS1000449393 (12:14973770 A>G), RS1000734468 (12:14972097 T>A,G), RS1001173494 (12:14973673 T>G), RS1001189427 (12:14972401 C>T), RS1001288570 (12:14979706 A>T), RS1002177754 (12:14972432 T>A), RS1002193962 (12:14976530 C>T), RS1002246379 (12:14976785 T>A,G), RS1002458627 (12:14971051 G>A), RS1002526221 (12:14975364 T>C), RS1003292453 (12:14976698 TA>T,TAA), RS1003382147 (12:14971387 A>G), RS1003461667 (12:14976476 A>G), RS1003882055 (12:14979962 T>G)

Disease associations

OMIM: gene MIM:601190 | disease phenotypes: MIM:610024

GenCC curated gene-disease

Disease	Classification	Inheritance
achromatopsia 6	Strong	Autosomal recessive
achromatopsia	Strong	Autosomal recessive

Mondo (3): achromatopsia 6 (MONDO:0012398), inherited retinal dystrophy (MONDO:0019118), achromatopsia (MONDO:0018852)

Orphanet (2): Achromatopsia (Orphanet:49382), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

29 total (30 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000539	Abnormality of refraction
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001103	Abnormal macular morphology
HP:0003621	Juvenile onset
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007695	Abnormal pupillary light reflex
HP:0007722	Retinal pigment epithelial atrophy
HP:0007750	Hypoplasia of the fovea
HP:0007803	Monochromacy
HP:0007814	Retinal pigment epithelial mottling
HP:0007843	Attenuation of retinal blood vessels
HP:0008020	Cone dystrophy
HP:0011003	High myopia
HP:0012043	Pendular nystagmus
HP:0025549	Eccentric visual fixation
HP:0030465	Undetectable light-adapted electroretinogram
HP:0030473	Abnormal light-adapted flicker electroretinogram
HP:0030584	Color vision test abnormality
HP:0030620	Inner retinal layer loss on macular OCT
HP:0030825	Absent foveal reflex
HP:0000556	Retinal dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C566483	Retinal Cone Dystrophy 3A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095220 (SELECTIVITY GROUP), CHEMBL2097163 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY)

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

102 potent at pChembl≥5 of 110 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	620	nM	CHEMBL285737
6.16	IC50	693	nM	CHEMBL2070654
6.16	Ki	697	nM	CHEMBL1939804
6.13	IC50	734	nM	CHEMBL2070641

PubChem BioAssay actives

102 with measured affinity, of 185 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

51 unique, capped per target: 49 binding, 2 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)

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

Trial	Phase	Status	Title
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]
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)
NCT01648452	PHASE1/PHASE2	COMPLETED	CNTF Implants for CNGB3 Achromatopsia
NCT02599922	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)
NCT02610582	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of rAAV.hCNGA3 Gene Therapy in Patients With CNGA3-linked Achromatopsia
NCT02935517	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)
NCT03001310	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGB3)
NCT03758404	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGA3)
NCT04041232	EARLY_PHASE1	SUSPENDED	PBA Use for Treatment of ATF6-/- Patients
NCT01846052	Not specified	COMPLETED	Clinical and Genetic Characterization of Individuals With Achromatopsia
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03278873	Not specified	TERMINATED	Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3
NCT04124185	Not specified	COMPLETED	Natural History Study for Achromatopsia
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
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.
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
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics