PDE6C

Summary

PDE6C (phosphodiesterase 6C, HGNC:8787) is a protein-coding gene on chromosome 10q23.33, encoding Cone cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha’ (P51160). As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.

This gene encodes the alpha-prime subunit of cone phosphodiesterase, which is composed of a homodimer of two alpha-prime subunits and 3 smaller proteins of 11, 13, and 15 kDa. Mutations in this gene are associated with cone dystrophy type 4 (COD4).

Source: NCBI Gene 5146 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PDE6C-related retinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 759 total — 58 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8787
Approved symbol	PDE6C
Name	phosphodiesterase 6C
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	PDEA2, ACHM5, COD4
Ensembl gene	ENSG00000095464
Ensembl biotype	protein_coding
OMIM	600827
Entrez	5146

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371447, ENST00000475427

RefSeq mRNA: 1 — MANE Select: NM_006204 NM_006204

CCDS: CCDS7429

Canonical transcript exons

ENST00000371447 — 22 exons

Exon	Start	End
ENSE00000715252	93645960	93646047
ENSE00000932982	93620632	93620784
ENSE00000932983	93620891	93620980
ENSE00000932984	93621932	93622072
ENSE00000932985	93625575	93625649
ENSE00000932986	93626640	93626704
ENSE00000932987	93626805	93626871
ENSE00000932992	93636995	93637063
ENSE00000932993	93640070	93640216
ENSE00000986681	93655760	93655860
ENSE00000986682	93658901	93659008
ENSE00001124082	93640920	93641029
ENSE00001162365	93663028	93663178
ENSE00001162387	93612537	93613205
ENSE00001196167	93635497	93635640
ENSE00001283040	93640450	93640557
ENSE00001283078	93629258	93629305
ENSE00001384351	93634758	93634907
ENSE00001838714	93665360	93666010
ENSE00002471733	93659104	93659167
ENSE00003585115	93662059	93662133
ENSE00003626221	93662560	93662643

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 77.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0054 / max 4.5762, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106290	0.0054	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	77.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.71	gold quality
cerebellar hemisphere	UBERON:0002245	74.68	gold quality
cerebellar cortex	UBERON:0002129	74.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.99	gold quality
cerebellum	UBERON:0002037	71.34	gold quality
ectocervix	UBERON:0012249	67.90	gold quality
tibial nerve	UBERON:0001323	67.11	gold quality
right lung	UBERON:0002167	66.85	gold quality
gastrocnemius	UBERON:0001388	66.65	gold quality
endocervix	UBERON:0000458	66.36	gold quality
muscle of leg	UBERON:0001383	65.92	gold quality
body of uterus	UBERON:0009853	65.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.47	gold quality
lower esophagus	UBERON:0013473	65.41	gold quality
descending thoracic aorta	UBERON:0002345	65.14	gold quality
skin of leg	UBERON:0001511	64.84	gold quality
tibial artery	UBERON:0007610	64.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	64.72	gold quality
popliteal artery	UBERON:0002250	64.70	gold quality
skin of abdomen	UBERON:0001416	64.68	gold quality
metanephros cortex	UBERON:0010533	64.59	gold quality
aorta	UBERON:0000947	64.26	gold quality
ascending aorta	UBERON:0001496	64.18	gold quality
stromal cell of endometrium	CL:0002255	64.14	gold quality
thoracic aorta	UBERON:0001515	63.99	gold quality
left ovary	UBERON:0002119	63.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	63.51	gold quality
calcaneal tendon	UBERON:0003701	63.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	63.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.97
E-GEOD-111727	no	390.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting PDE6C, 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-3662	99.99	73.82	5684
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-621	96.76	66.89	371
HSA-MIR-664B-5P	96.74	67.50	509

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 17)

• Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. (PMID:19615668)
• analysis of human cone phosphodiesterase-6 ectopically expressed in Xenopus laevis rods (PMID:19801642)
• the identification of mutations in the PDE6C gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase as a cause of autosomal recessive achromatopsia was reported. (PMID:19887631)
• Eleven different PDE6C mutations were found including two nonsense mutations, three mutations affecting transcript splicing as shown by minigene assays, one 1 bp-insertion and five missense mutations (PMID:21127010)
• Missense mutations, nonsense mutations, splice mutations, and small deletions and insertions in the affected genes cause achromatopsia. (PMID:21267001)
• analysis of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6 (PMID:23033484)
• The majority (n = 12) of patients were either homozygotes or compound heterozygotes for known achromatopsia alleles, two in CNGB3 (p.T383fsX and p.T296YfsX9) and three in CNGA3 (p.R283Q, p.R427C and p.L527R). (PMID:23362848)
• A novel homozygous PDE6C mutation was identified as the cause of ACHM. In addition, we identified an OPN1SW mutation in the sibling with complete achromatopsia. (PMID:25605338)
• Expression of PDE6 in rod photoreceptors show that the cone PDE6 isoform is responsible for the difference in light adaptation between rods and cones. (PMID:26085644)
• This study reveals two general mechanisms of missense PDE6C mutations underlying retinal diseases: (a) inability of AIPL1 to fold mutant PDE6C proteins leading to complete catalytic inactivity and (b) failure of P gamma regulatory subunit to serve as co-chaperone with AIPL1 in folding of mutant PDE6C. (PMID:28583373)
• Three novel homozygous variants were detected in CNGA3, two novel variants were found in PDE6C. All patients had nonrecordable full-field electroretinography 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. (PMID:30289319)
• Novel Bi-allelic PDE6C Variant Leads to Congenital Achromatopsia. (PMID:32306724)
• Two novel PDE6C gene mutations in Chinese family with achromatopsia. (PMID:32787476)
• PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults. (PMID:33001157)
• An enhancer located in a Pde6c intron drives transient expression in the cone photoreceptors of developing mouse and human retinas. (PMID:35644251)
• Reconstitution of the phosphodiesterase 6 maturation process important for photoreceptor cell function. (PMID:38110033)
• Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia. (PMID:38956522)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde6c	ENSDARG00000100397
mus_musculus	Pde6c	ENSMUSG00000024992
rattus_norvegicus	Pde6c	ENSRNOG00000016593
drosophila_melanogaster	Pde11	FBGN0085370
drosophila_melanogaster	Pde8	FBGN0266377
caenorhabditis_elegans		WBGENE00008443
caenorhabditis_elegans	pde-6	WBGENE00022389

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE4C (ENSG00000105650), PDE10A (ENSG00000112541), PDE8B (ENSG00000113231), PDE4D (ENSG00000113448), PDE1A (ENSG00000115252), PDE1B (ENSG00000123360), PDE11A (ENSG00000128655), PDE6A (ENSG00000132915), PDE6B (ENSG00000133256), PDE5A (ENSG00000138735), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

Cone cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha’ — P51160 (reviewed: P51160)

Alternative names: cGMP phosphodiesterase 6C

All UniProt accessions (1): P51160

UniProt curated annotations — full annotation on UniProt →

Function. As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.

Subunit / interactions. Composed of two alpha’ subunits that are associated with 3 smaller proteins of 11, 13, and 15 kDa.

Subcellular location. Cell membrane.

Disease relevance. Cone dystrophy 4 (COD4) [MIM:613093] An early-onset cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs. The disease is caused by variants affecting the gene represented in this entry. Achromatopsia 5 (ACHM5) [MIM:613093] A form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. ACHM5 inheritance is autosomal recessive. 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.

RefSeq proteins (1): NP_006195* (*=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 (106 total): helix 39, strand 21, sequence variant 15, binding site 9, turn 7, sequence conflict 4, domain 3, chain 1, propeptide 1, modified residue 1, lipid moiety-binding region 1, mutagenesis site 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5E8F	X-RAY DIFFRACTION	2.1
3JWQ	X-RAY DIFFRACTION	2.87
3JWR	X-RAY DIFFRACTION	2.99
9CXG	ELECTRON MICROSCOPY	3
9CXI	ELECTRON MICROSCOPY	3
9CXH	ELECTRON MICROSCOPY	3.1
9CXJ	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51160-F1	88.53	0.63

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): 562 (proton donor)

Ligand- & substrate-binding residues (9): 169–172; 176; 566; 602; 603; 603; 723; 97; 116

Post-translational modifications (2): 855, 855

Mutagenesis-validated functional residues (1):

Position	Phenotype
858	no effect on cgmp phosphodiesterase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_PHOTOTRANSDUCTION, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, PID_CONE_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_RESPONSE_TO_RADIATION, GOBP_CAMERA_TYPE_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, CYTAGCAAY_UNKNOWN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (6): visual perception (GO:0007601), phototransduction, visible light (GO:0007603), retinal cone cell development (GO:0046549), negative regulation of cAMP/PKA signal transduction (GO:0141162), signal transduction (GO:0007165), sensory perception of light stimulus (GO:0050953)

GO Molecular Function (9): 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), cGMP binding (GO:0030553), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), nucleotide binding (GO:0000166), 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 (3): plasma membrane (GO:0005886), photoreceptor disc membrane (GO:0097381), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
sensory perception of light stimulus	1
phototransduction	1
detection of visible light	1
eye photoreceptor cell development	1
retinal cone cell differentiation	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception	1
cyclic nucleotide binding	1
guanyl ribonucleotide binding	1
anion binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cyclic-nucleotide phosphodiesterase activity	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
membrane	1
cell periphery	1
photoreceptor outer segment	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE6C	CNGB3	Q9NQW8	983
PDE6C	GNAT2	P19087	980
PDE6C	CNGA3	Q16281	975
PDE6C	PDE6H	Q13956	916
PDE6C	FRA10AC1	Q70Z53	826
PDE6C	ALDH7A1	P49419	749
PDE6C	OPN4	Q9UHM6	731
PDE6C	CNGB1	Q14028	724
PDE6C	CNGA1	P29973	683
PDE6C	ARR3	P36575	680
PDE6C	GLYATL1	Q969I3	668
PDE6C	PDE6D	O43924	646
PDE6C	RHO	P08100	630
PDE6C	ROM1	Q03395	617
PDE6C	GUCY2D	Q02846	610

IntAct

0 interactions, top by confidence:

BioGRID (9): PDE6C (Reconstituted Complex), PDE6C (Affinity Capture-MS), ATP5A1 (Cross-Linking-MS (XL-MS)), BTF3 (Cross-Linking-MS (XL-MS)), BTF3L4 (Cross-Linking-MS (XL-MS)), PDE6C (Cross-Linking-MS (XL-MS)), PDE6C (Cross-Linking-MS (XL-MS)), PDE6C (Cross-Linking-MS (XL-MS)), PDE6C (Co-fractionation)

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

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

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	35
Uncertain significance	325
Likely benign	247
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070811	NM_006204.4(PDE6C):c.1870del (p.Leu624fs)	Pathogenic
1213877	NM_006204.4(PDE6C):c.480G>T (p.Lys160Asn)	Pathogenic
1298495	NM_006204.4(PDE6C):c.2445del (p.Ala816fs)	Pathogenic
1351127	NM_006204.4(PDE6C):c.1921_1922del (p.Leu641fs)	Pathogenic
1373411	NM_006204.4(PDE6C):c.2435G>A (p.Trp812Ter)	Pathogenic
1408090	NM_006204.4(PDE6C):c.2136_2140del (p.Glu712fs)	Pathogenic
1451335	NM_006204.4(PDE6C):c.2059del (p.Ile687fs)	Pathogenic
1453230	NM_006204.4(PDE6C):c.1727del (p.Thr576fs)	Pathogenic
1456127	NM_006204.4(PDE6C):c.549del (p.Ile184fs)	Pathogenic
1457707	NM_006204.4(PDE6C):c.1481del (p.Ile493_Leu494insTer)	Pathogenic
1458687	NM_006204.4(PDE6C):c.305G>A (p.Arg102Gln)	Pathogenic
1723179	NM_006204.4(PDE6C):c.480+1del	Pathogenic
1920033	NM_006204.4(PDE6C):c.1482+1del	Pathogenic
1995570	NM_006204.4(PDE6C):c.221del (p.Gly74fs)	Pathogenic
2007759	NM_006204.4(PDE6C):c.405_406del (p.Phe136fs)	Pathogenic
2095572	NM_006204.4(PDE6C):c.721C>T (p.Gln241Ter)	Pathogenic
2116444	NM_006204.4(PDE6C):c.1293del (p.Trp431fs)	Pathogenic
2119906	NM_006204.4(PDE6C):c.1756del (p.Tyr586fs)	Pathogenic
2425523	NC_000010.10:g.(?95361588)(95425175_?)del	Pathogenic
2628029	NM_006204.4(PDE6C):c.2368-2A>T	Pathogenic
2735456	NM_006204.4(PDE6C):c.310C>T (p.Arg104Trp)	Pathogenic
3244974	NC_000010.10:g.(?95405697)(95405824_?)del	Pathogenic
3249771	NM_006204.4(PDE6C):c.634-1G>C	Pathogenic
3249776	NM_006204.4(PDE6C):c.2489dup (p.Gln833fs)	Pathogenic
3249920	NM_006204.4(PDE6C):c.1659del (p.Tyr556fs)	Pathogenic
3336624	NM_006204.4(PDE6C):c.1483-1G>A	Pathogenic
3381815	NM_006204.4(PDE6C):c.2361_2363dup (p.Tyr788Ter)	Pathogenic
3381816	NM_006204.4(PDE6C):c.633G>A (p.Glu211=)	Pathogenic
3631169	NM_006204.4(PDE6C):c.1574del (p.Gly525fs)	Pathogenic
3651657	NM_006204.4(PDE6C):c.246_247del (p.Arg82fs)	Pathogenic

SpliceAI

2974 predictions. Top by Δscore:

Variant	Effect	Δscore
10:93613202:AAAGG:A	donor_loss	1.0000
10:93613205:GGT:G	donor_loss	1.0000
10:93613206:GTA:G	donor_loss	1.0000
10:93620626:TTTCA:T	acceptor_loss	1.0000
10:93620627:TTCA:T	acceptor_loss	1.0000
10:93620628:TCA:T	acceptor_loss	1.0000
10:93620629:CA:C	acceptor_loss	1.0000
10:93620630:A:AC	acceptor_loss	1.0000
10:93620630:A:AG	acceptor_gain	1.0000
10:93620631:G:GA	acceptor_gain	1.0000
10:93620631:G:GT	acceptor_loss	1.0000
10:93620631:GAAC:G	acceptor_gain	1.0000
10:93620631:GAACA:G	acceptor_gain	1.0000
10:93621916:T:A	acceptor_gain	1.0000
10:93621925:C:G	acceptor_gain	1.0000
10:93621927:TTCA:T	acceptor_loss	1.0000
10:93621928:TCA:T	acceptor_loss	1.0000
10:93621929:CA:C	acceptor_loss	1.0000
10:93621930:A:AC	acceptor_loss	1.0000
10:93621930:A:AG	acceptor_gain	1.0000
10:93621931:G:GA	acceptor_gain	1.0000
10:93621931:GAT:G	acceptor_gain	1.0000
10:93621931:GATC:G	acceptor_gain	1.0000
10:93621931:GATCC:G	acceptor_gain	1.0000
10:93622067:G:GT	donor_gain	1.0000
10:93622068:A:T	donor_gain	1.0000
10:93622069:G:GT	donor_gain	1.0000
10:93622070:A:T	donor_gain	1.0000
10:93625645:GCAGG:G	donor_gain	1.0000
10:93625648:GG:G	donor_gain	1.0000

AlphaMissense

5737 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:93640504:C:G	H562D	1.000
10:93640990:A:C	D603A	1.000
10:93640990:A:T	D603V	1.000
10:93641015:T:A	N611K	1.000
10:93641015:T:G	N611K	1.000
10:93646004:A:T	E631V	1.000
10:93655839:C:T	T672I	1.000
10:93655842:A:G	D673G	1.000
10:93659127:A:C	D723A	1.000
10:93659127:A:T	D723V	1.000
10:93662083:T:C	F745L	1.000
10:93662085:T:A	F745L	1.000
10:93662085:T:G	F745L	1.000
10:93662611:T:C	F779L	1.000
10:93662613:T:A	F779L	1.000
10:93662613:T:G	F779L	1.000
10:93662624:T:A	V783D	1.000
10:93663094:T:A	W812R	1.000
10:93663094:T:C	W812R	1.000
10:93622035:G:C	R276P	0.999
10:93622040:T:C	S278P	0.999
10:93640462:T:A	W548R	0.999
10:93640462:T:C	W548R	0.999
10:93640506:C:A	H562Q	0.999
10:93640506:C:G	H562Q	0.999
10:93640510:T:A	W564R	0.999
10:93640510:T:C	W564R	0.999
10:93640986:C:G	H602D	0.999
10:93640989:G:C	D603H	0.999
10:93640990:A:G	D603G	0.999

dbSNP variants (sampled 300 via entrez): RS1000023418 (10:93620318 C>CT), RS1000140635 (10:93647820 A>C), RS1000172239 (10:93648340 G>A,T), RS1000174370 (10:93654680 G>A), RS1000229704 (10:93661910 T>C), RS1000305847 (10:93626244 T>C), RS1000308477 (10:93655220 G>A), RS1000400200 (10:93641665 A>G), RS1000414467 (10:93648316 C>A), RS1000472501 (10:93646730 A>C), RS1000502986 (10:93656344 G>A,C), RS1000505199 (10:93646957 G>C), RS1000578354 (10:93621749 C>T), RS1000608204 (10:93655177 C>T), RS1000694868 (10:93620540 T>C)

Disease associations

OMIM: gene MIM:600827 | disease phenotypes: MIM:613093

GenCC curated gene-disease

Disease	Classification	Inheritance
cone dystrophy 4	Definitive	Autosomal recessive
cone dystrophy	Supportive	Autosomal dominant
achromatopsia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
PDE6C-related retinopathy	Definitive	AR

Mondo (7): inherited retinal dystrophy (MONDO:0019118), cone dystrophy 4 (MONDO:0013129), achromatopsia (MONDO:0018852), optic atrophy (MONDO:0003608), cone dystrophy (MONDO:0000455), isolated macular dystrophy (MONDO:0957048), achromatopsia 5 (MONDO:0800196)

Orphanet (4): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Achromatopsia (Orphanet:49382), Progressive cone dystrophy (Orphanet:1871), OBSOLETE: Isolated macular dystrophy (Orphanet:519302)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000539	Abnormality of refraction
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000548	Cone/cone-rod dystrophy
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0001103	Abnormal macular morphology
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007695	Abnormal pupillary light reflex
HP:0007703	Abnormal retinal pigmentation
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:0011463	Childhood onset
HP:0012043	Pendular nystagmus
HP:0025549	Eccentric visual fixation
HP:0030465	Undetectable light-adapted 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

3 associations (top):

Study	Trait	p-value
GCST006996_2	Cerebrospinal AB1-42 levels in mild cognitive impairment	3.000000e-07
GCST007012_3	Cerebrospinal fluid AB1-42 levels	7.000000e-06
GCST010002_297	Refractive error	3.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
C567758	Cone Dystrophy 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095220 (SELECTIVITY GROUP), CHEMBL2097163 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3977 (SINGLE PROTEIN), CHEMBL4523626 (CHIMERIC PROTEIN)

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)

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
sildenafil	Inhibition	7.41	pIC50
PDE4 inhibitor 16	Inhibition	5.48	pIC50

ChEMBL bioactivities

145 potent at pChembl≥5 of 156 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
9.89	IC50	0.13	nM	CHEMBL3936651
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
9.05	IC50	0.9	nM	CHEMBL377168
9.00	IC50	1	nM	VARDENAFIL
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742
8.92	IC50	1.2	nM	CHEMBL4217054
8.92	IC50	1.2	nM	CHEMBL4218772
8.85	IC50	1.4	nM	CHEMBL209460
8.85	IC50	1.4	nM	CHEMBL4212186
8.82	IC50	1.5	nM	CHEMBL4217579
8.66	IC50	2.2	nM	CHEMBL2414311
8.64	IC50	2.3	nM	CHEMBL4212630
8.59	IC50	2.6	nM	CHEMBL3900593
8.43	IC50	3.7	nM	CHEMBL4218398
8.42	IC50	3.8	nM	CHEMBL4208249
8.32	IC50	4.8	nM	CHEMBL4209716
8.28	IC50	5.2	nM	CHEMBL3401745
8.21	IC50	6.2	nM	CHEMBL4204725
8.18	IC50	6.6	nM	CHEMBL4072903
8.13	IC50	7.4	nM	CHEMBL2180942
8.02	IC50	9.5	nM	SILDENAFIL
8.00	IC50	10	nM	CHEMBL4284224
7.96	IC50	11	nM	VARDENAFIL
7.89	IC50	13	nM	CHEMBL4285199
7.70	IC50	19.8	nM	CHEMBL4462192
7.70	IC50	20	nM	CHEMBL6103021
7.62	IC50	24	nM	SILDENAFIL
7.60	IC50	25	nM	SILDENAFIL
7.60	Ki	25	nM	SILDENAFIL
7.52	IC50	30.1	nM	CHEMBL4062273
7.47	IC50	34.1	nM	CHEMBL4205338
7.44	IC50	36.42	nM	SILDENAFIL
7.41	IC50	39.2	nM	SILDENAFIL
7.40	IC50	40	nM	SILDENAFIL
7.34	IC50	45.6	nM	CHEMBL2180945
7.30	Ki	50	nM	SILDENAFIL
7.25	IC50	56	nM	CHEMBL4277243
7.21	IC50	62	nM	CHEMBL213060
7.21	IC50	62	nM	CHEMBL4292389
7.14	IC50	73.15	nM	CHEMBL2069321
7.05	IC50	90	nM	CHEMBL5647232
6.97	IC50	107	nM	CHEMBL4280648
6.90	Ki	125	nM	DIPYRIDAMOLE

PubChem BioAssay actives

144 with measured affinity, of 320 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
2-[4-[4-ethoxy-3-(3-ethyl-1-methyl-7-oxo-6H-pyrazolo[4,5-d]pyrimidin-5-yl)phenoxy]piperidin-1-yl]-N-hydroxypyrimidine-5-carboxamide	1321751: Inhibition of recombinant N-terminal GST tagged PDE6C (unknown origin) expressed in baculovirus infected Sf9 cells using cGMP as substrate by malachite green reagent based assay	ic50	0.0001	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]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
5-(5-acetyl-2-ethoxyphenyl)-1-methyl-3-propyl-6H-pyrazolo[4,5-d]pyrimidin-7-one	266177: Inhibition of canine retinal cone PDE6	ic50	0.0009	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
3-(1,3-benzodioxol-5-ylmethyl)-8-hydroxy-6-(2-methoxyethylamino)-1-(1,3-thiazol-2-yl)-2H-chromeno[2,3-c]pyrrol-9-one	1386222: Inhibition of PDE6C catalytic domain (1 to 858 residues) (unknown origin) expressed in Escherichia coli BL21 using 3H-cGMP as substrate after 15 mins by liquid scintillation counting	ic50	0.0012	uM
(3S)-3-(5-ethylthiophen-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0012	uM
5-[2-ethoxy-5-(2-morpholin-4-ylacetyl)phenyl]-1-methyl-3-propyl-6H-pyrazolo[4,5-d]pyrimidin-7-one	266177: Inhibition of canine retinal cone PDE6	ic50	0.0014	uM
5-[[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6H-pyrazolo[4,5-d]pyrimidin-5-yl)phenyl]methyl]-N-hydroxythiophene-2-carboxamide	1384250: Inhibition of PDE6C (unknown origin) using FAM-cGMP as substrate by fluorescence assay	ic50	0.0014	uM
(3S)-3-(5-ethylfuran-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0015	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
3-(5-ethylfuran-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0023	uM
3-[[4-ethoxy-3-(3-ethyl-1-methyl-7-oxo-6H-pyrazolo[4,5-d]pyrimidin-5-yl)phenyl]methyl]-N-hydroxycyclobutane-1-carboxamide	1321751: Inhibition of recombinant N-terminal GST tagged PDE6C (unknown origin) expressed in baculovirus infected Sf9 cells using cGMP as substrate by malachite green reagent based assay	ic50	0.0026	uM
3-(5-ethylthiophen-2-yl)-2-pyrimidin-2-yl-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0037	uM
(3R)-3-(5-ethylfuran-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0038	uM
3-(5-ethylthiophen-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0048	uM
4-ethoxy-N-(6-hydroxyhexyl)-3-(1-methyl-7-oxo-3-propyl-6H-pyrazolo[4,5-d]pyrimidin-5-yl)benzenesulfonamide	1194411: Inhibition of PDE6C (unknown origin)	ic50	0.0052	uM
3-(5-ethylfuran-2-yl)-2-pyrimidin-2-yl-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0062	uM
9-[(3-chloro-4-methoxyphenyl)methylamino]-2-ethyl-1-oxo-3H-pyrrolo[3,4-b]quinoline-7-carbonitrile	1465726: Inhibition of human recombinant PDE6C using FAM-labelled cGMP as substrate after 60 mins by fluorescence polarization assay	ic50	0.0066	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
(10R,15R)-13-ethyl-10-(5-ethylfuran-2-yl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0100	uM
(10S,15S)-13-ethyl-10-(3-methylthiophen-2-yl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0130	uM
N-[3-(4,5-diethyl-6-oxo-1H-pyrimidin-2-yl)-4-propoxyphenyl]-2-(4-methylpiperazin-1-yl)acetamide	1598439: Inhibition of N-terminal GST-tagged human PDE6C expressed in baculovirus infected sf9 cells using [3H]cGMP as substrate measured after 30 mins by scintillation proximity assay	ic50	0.0198	uM
2-acetyl-10-[(3-chloro-4-methoxyphenyl)methylamino]-3,4-dihydro-1H-benzo[b][1,6]naphthyridine-8-carbonitrile	1465726: Inhibition of human recombinant PDE6C using FAM-labelled cGMP as substrate after 60 mins by fluorescence polarization assay	ic50	0.0301	uM
(3R)-3-(5-ethylthiophen-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	1383532: Inhibition of N-terminal GST-tagged full length recombinant human PDE6C expressed in Baculovirus infected Sf9 insect cells using FAM-cAMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0341	uM
4,5-diethyl-2-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-1H-pyrimidin-6-one	709828: Inhibition of human recombinant PDE6C at 1 uM by [3H]cGMP based tritium scintillation proximity assay	ic50	0.0456	uM
(10S,15S)-13-ethyl-10-(5-ethylthiophen-2-yl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.0560	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
(10S,15S)-13-ethyl-10-(5-methylfuran-2-yl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	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
2-[bis(2-hydroxyethyl)amino]-6-[(4-methoxyphenyl)methylamino]-9-propan-2-yl-7H-purin-8-one	2143646: Inhibition of full-length recombinant human PDE6C using [3H]-cGMP as substrate incubated for 10 mins by SPA assay	ic50	0.0900	uM
(10S,15S)-13-butyl-10-(5-ethylthiophen-2-yl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.1070	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
(10S,15S)-13-ethyl-10-(5-ethylfuran-2-yl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.1270	uM
(2S,8R)-2-(5-bromothiophen-2-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.1360	uM
2-[2-hydroxyethyl-[4-[(4-methoxyphenyl)methylamino]-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]amino]ethanol	2143646: Inhibition of full-length recombinant human PDE6C using [3H]-cGMP as substrate incubated for 10 mins by SPA assay	ic50	0.1600	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
5-(5-acetyl-2-butoxy-3-pyridinyl)-3-propyl-2-(pyridin-2-ylmethyl)-6H-pyrazolo[4,3-d]pyrimidin-7-one	266177: Inhibition of canine retinal cone PDE6	ic50	0.1830	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
2-[5-(3,4-dimethoxyphenyl)pyrimidin-2-yl]-1-(5-ethylthiophen-2-yl)-3,9-dihydro-1H-pyrido[3,4-b]indol-4-one	1421858: Inhibition of full length recombinant human N-terminal GST-tagged PDE6C expressed in baculovirus infected sf9 cells using FAM-cyclic-3’,5-AMP as substrate after 1 hr by fluorescence polarization assay	ic50	0.2530	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Aflatoxin B1	increases expression, increases methylation	3
Cadmium	increases abundance, increases palmitoylation, decreases expression, decreases reaction	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
graphene oxide	increases expression	1
triphenyl phosphate	affects expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
perfluorohexanesulfonic acid	increases expression	1
Atrazine	increases expression	1
Estradiol	decreases expression	1
Formaldehyde	increases expression	1
Malathion	decreases expression	1
Methamphetamine	affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	decreases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

103 unique, capped per target: 97 binding, 6 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

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_XJ80	FRIMOi007-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

63 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)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03990727	Not specified	UNKNOWN	Phenotype Correlates Genotype of Inherited Retina Dystrophies, Retinitis Pigmentosa, Con>Rod Dystrophies.
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
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
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