PDE6A

Summary

PDE6A (phosphodiesterase 6A, HGNC:8785) is a protein-coding gene on chromosome 5q32, encoding Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha (P16499). Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.

This gene encodes the cyclic-GMP (cGMP)-specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 holoenzyme is a heterotrimer composed of an alpha, beta, and two gamma subunits. cGMP is an important regulator of rod cell membrane current, and its dynamic concentration is established by phosphodiesterase 6A cGMP hydrolysis and guanylate cyclase cGMP synthesis. The protein is a subunit of a key phototransduction enzyme and participates in processes of transmission and amplification of the visual signal. Mutations in this gene have been identified as one cause of autosomal recessive retinitis pigmentosa.

Source: NCBI Gene 5145 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PDE6A-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 980 total — 80 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000440

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8785
Approved symbol	PDE6A
Name	phosphodiesterase 6A
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	RP43
Ensembl gene	ENSG00000132915
Ensembl biotype	protein_coding
OMIM	180071
Entrez	5145

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000255266, ENST00000508173, ENST00000512670, ENST00000613228, ENST00000890426

RefSeq mRNA: 2 — MANE Select: NM_000440 NM_000440, NM_001410788

CCDS: CCDS4299, CCDS93802

Canonical transcript exons

ENST00000255266 — 22 exons

Exon	Start	End
ENSE00000906317	149898363	149898506
ENSE00000906318	149896711	149896776
ENSE00000906319	149896356	149896502
ENSE00003461783	149863119	149863266
ENSE00003472471	149886265	149886374
ENSE00003479230	149921635	149921709
ENSE00003491729	149857953	149860971
ENSE00003507079	149884780	149884867
ENSE00003508743	149944200	149944793
ENSE00003543490	149934566	149934718
ENSE00003559100	149907312	149907378
ENSE00003575680	149895183	149895290
ENSE00003591201	149868095	149868158
ENSE00003615613	149884479	149884579
ENSE00003615779	149899375	149899524
ENSE00003617448	149866170	149866253
ENSE00003619852	149883429	149883536
ENSE00003621465	149933930	149934019
ENSE00003641404	149867725	149867799
ENSE00003646675	149914943	149915007
ENSE00003665691	149903648	149903695
ENSE00003673991	149931028	149931168

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 82.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6088 / max 642.9158, expressed in 21 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64142	0.5251	16
64143	0.0669	5
64136	0.0114	3
64135	0.0054	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	82.10	gold quality
cauda epididymis	UBERON:0004360	77.64	gold quality
endometrium epithelium	UBERON:0004811	71.87	gold quality
mucosa of transverse colon	UBERON:0004991	71.35	gold quality
frontal pole	UBERON:0002795	71.26	gold quality
paraflocculus	UBERON:0005351	70.71	gold quality
middle frontal gyrus	UBERON:0002702	70.25	gold quality
colonic mucosa	UBERON:0000317	67.48	gold quality
mucosa of sigmoid colon	UBERON:0004993	65.00	silver quality
Brodmann (1909) area 10	UBERON:0013541	64.36	gold quality
tibialis anterior	UBERON:0001385	64.11	silver quality
rectum	UBERON:0001052	63.95	gold quality
right adrenal gland cortex	UBERON:0035827	63.92	gold quality
sperm	CL:0000019	62.54	silver quality
right adrenal gland	UBERON:0001233	62.36	gold quality
male germ cell	CL:0000015	61.69	silver quality
ileal mucosa	UBERON:0000331	61.14	silver quality
left testis	UBERON:0004533	60.73	gold quality
transverse colon	UBERON:0001157	60.64	gold quality
right testis	UBERON:0004534	60.36	gold quality
testis	UBERON:0000473	59.83	gold quality
pituitary gland	UBERON:0000007	58.90	gold quality
adenohypophysis	UBERON:0002196	58.76	gold quality
left adrenal gland cortex	UBERON:0035825	58.50	gold quality
adrenal cortex	UBERON:0001235	58.28	gold quality
esophagus mucosa	UBERON:0002469	58.12	gold quality
oral cavity	UBERON:0000167	57.44	silver quality
caput epididymis	UBERON:0004358	57.40	gold quality
quadriceps femoris	UBERON:0001377	57.08	gold quality
left adrenal gland	UBERON:0001234	56.55	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	8149.25
E-GEOD-137537	yes	5865.86
E-MTAB-7316	yes	5172.10
E-HCAD-38	yes	272.47
E-GEOD-124858	no	14.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

97 targeting PDE6A, 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-3134	100.00	66.43	777
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 15)

• full transcriptional activity of the PDE6A gene requires both Nrl and Crx (PMID:15001570)
• Homozygous single base pair change; c.889C->T, single base pair insertion; c.2218-2219insT, and single base pair substitution in the splice acceptor site; IVS10-2A->G in each of three families. (PMID:17110911)
• Rod phosphodiesterase-6 PDE6A and PDE6B subunits are enzymatically equivalent. (PMID:20940301)
• the p.Val685Met mutation in PDE6A causes retinal degeneration in humans (PMID:21039428)
• analysis of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6 (PMID:23033484)
• report two splice acceptor site variations in PDE6A in consanguineous Pakistani families who manifested cardinal symptoms of autosomal recessive retinitis pigmentosa (PMID:26321862)
• this is the first phenotypic description of arRP due to homozygous IVS6+1G>A mutations in PDE6A and these seem here to be associated with severe RP leading to early extinction of rod responses as well as reduced macular function. (PMID:27820873)
• By using targeted next-generation sequencing (NGS) method, we identified a compound heterozygous mutation in PDE6A gene that is associated with retinitis pigmentosa in a Chinese family. (PMID:29693493)
• Mutation in PDE6A gene is associated with autosomal recessive retinitis pigmentosa disease progression. (PMID:30153077)
• Co-Existence of Novel PDE6A Mutations and A Recurrent RPGR Mutation: A Potential Explanation for Phenotypic Diversity in Female RPGR Mutation Carriers. (PMID:30289068)
• 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 Phenotype and Course of PDE6A-Associated Retinitis Pigmentosa Disease, Characterized in Preparation for a Gene Supplementation Trial. (PMID:33057649)
• Photoreceptor Phosphodiesterase (PDE6): Structure, Regulatory Mechanisms, and Implications for Treatment of Retinal Diseases. (PMID:34170501)
• Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families. (PMID:35033039)
• Central Visual Function and Genotype-Phenotype Correlations in PDE6A-Associated Retinitis Pigmentosa. (PMID:35533076)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pde6a	ENSMUSG00000024575
rattus_norvegicus	Pde6a	ENSRNOG00000017816
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), PDE6B (ENSG00000133256), 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 alpha — P16499 (reviewed: P16499)

Alternative names: PDE V-B1

All UniProt accessions (2): P16499, F1T0K3

UniProt curated annotations — full annotation on UniProt →

Function. Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP. This protein participates 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. Cell membrane. Cell projection. Cilium. Photoreceptor outer segment.

Disease relevance. Retinitis pigmentosa 43 (RP43) [MIM:613810] 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.

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 (2): NP_000431, NP_001397717 (=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 (31 total): sequence variant 13, binding site 5, domain 3, modified residue 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, propeptide 1, sequence conflict 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16499-F1	89.80	0.69

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): 559 (proton donor)

Ligand- & substrate-binding residues (5): 599; 600; 600; 720; 563

Post-translational modifications (3): 2, 857, 857

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: 183 (showing top): MORF_MSH3, MORF_BRCA1, MORF_RAD51L3, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MORF_CTSB, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, MORF_IL4, MORF_PRKCA, MORF_THPO, KEGG_PURINE_METABOLISM, HOEGERKORP_CD44_TARGETS_DIRECT_UP, NGUYEN_NOTCH1_TARGETS_DN, GOBP_SENSORY_PERCEPTION, SABATES_COLORECTAL_ADENOMA_DN, GOCC_NEURON_PROJECTION

GO Biological Process (4): signal transduction (GO:0007165), visual perception (GO:0007601), retina development in camera-type eye (GO:0060041), negative regulation of cAMP/PKA signal transduction (GO:0141162)

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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of light stimulus	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
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

1018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE6A	PDE6G	P18545	980
PDE6A	CNGA1	P29973	852
PDE6A	CNGB1	Q14028	851
PDE6A	PDE6B	P35913	831
PDE6A	CERKL	Q49MI3	821
PDE6A	PRCD	Q00LT1	816
PDE6A	RPE65	Q16518	808
PDE6A	TULP1	O00294	801
PDE6A	EYS	Q5T1H1	790
PDE6A	PCARE	A6NGG8	781
PDE6A	IMPG2	Q9BZV3	779
PDE6A	RDH12	Q96NR8	777
PDE6A	GUCA1B	Q9UMX6	773
PDE6A	PRPH2	P23942	772
PDE6A	RPGR	Q92834	769

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CLOCK	BMAL1	psi-mi:“MI:0914”(association)	0.880
SMURF2	PDE6A	psi-mi:“MI:0407”(direct interaction)	0.440
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PDE6A (Affinity Capture-MS), PDE6A (Affinity Capture-MS), PDE6A (Affinity Capture-MS), PDE6A (Affinity Capture-MS), PDE6A (Proximity Label-MS), PDE6A (Affinity Capture-MS), PDE6A (Affinity Capture-MS), OGDH (Cross-Linking-MS (XL-MS)), PDE6A (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

1 interactions.

A	Effect	B	Mechanism
PDE6G	“down-regulates activity”	PDE6A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	80
Likely pathogenic	35
Uncertain significance	475
Likely benign	241
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1053825	NM_000440.3(PDE6A):c.1473+5G>A	Pathogenic
1065769	NM_000440.3(PDE6A):c.205C>T (p.Gln69Ter)	Pathogenic
1068664	NM_000440.3(PDE6A):c.1664del (p.Lys555fs)	Pathogenic
1068710	NM_000440.3(PDE6A):c.2426G>A (p.Trp809Ter)	Pathogenic
1070132	NM_000440.3(PDE6A):c.1561del (p.Cys521fs)	Pathogenic
1071791	NM_000440.3(PDE6A):c.1651_1652insCATG (p.Lys551delinsThrTer)	Pathogenic
1074528	NM_000440.3(PDE6A):c.2316_2317delinsAT (p.Gln773Ter)	Pathogenic
1075307	NM_000440.3(PDE6A):c.1989dup (p.Ile664fs)	Pathogenic
1075332	NM_000440.3(PDE6A):c.2036del (p.Thr679fs)	Pathogenic
1075610	NC_000005.9:g.(?149294506)(149294570_?)del	Pathogenic
1213871	NM_000440.3(PDE6A):c.1117G>T (p.Glu373Ter)	Pathogenic
1213872	NM_000440.3(PDE6A):c.1560dup (p.Cys521fs)	Pathogenic
1213873	NM_000440.3(PDE6A):c.2317C>T (p.Gln773Ter)	Pathogenic
13110	NM_000440.3(PDE6A):c.1749C>G (p.Tyr583Ter)	Pathogenic
13111	NM_000440.3(PDE6A):c.1032C>A (p.Ser344Arg)	Pathogenic
13112	NM_000440.3(PDE6A):c.1683G>A (p.Trp561Ter)	Pathogenic
1419945	NM_000440.3(PDE6A):c.1286G>A (p.Trp429Ter)	Pathogenic
1453359	NM_000440.3(PDE6A):c.1263+1G>A	Pathogenic
1455972	NM_000440.3(PDE6A):c.291del (p.Phe97fs)	Pathogenic
1456089	NM_000440.3(PDE6A):c.2263C>T (p.Gln755Ter)	Pathogenic
1457520	NC_000005.9:g.(?149260346)(149263094_?)del	Pathogenic
1457627	NM_000440.3(PDE6A):c.2306del (p.Leu769fs)	Pathogenic
1460102	NM_000440.3(PDE6A):c.2346dup (p.Phe783fs)	Pathogenic
1686015	NM_000440.3(PDE6A):c.1838+1G>A	Pathogenic
1937843	NM_000440.3(PDE6A):c.1359dup (p.Val454fs)	Pathogenic
194473	NM_000440.3(PDE6A):c.1926+1G>A	Pathogenic
1952061	NM_000440.3(PDE6A):c.1937del (p.Ile646fs)	Pathogenic
1995557	NM_000440.3(PDE6A):c.221_224del (p.Thr74fs)	Pathogenic
2005855	NM_000440.3(PDE6A):c.1311T>A (p.Tyr437Ter)	Pathogenic
2022827	NM_000440.3(PDE6A):c.1538del (p.Leu513fs)	Pathogenic

SpliceAI

3311 predictions. Top by Δscore:

Variant	Effect	Δscore
5:149860977:A:AC	acceptor_gain	1.0000
5:149863117:A:AT	donor_loss	1.0000
5:149863118:CC:C	donor_loss	1.0000
5:149863118:CCTGA:C	donor_gain	1.0000
5:149863262:AATTC:A	acceptor_gain	1.0000
5:149863263:ATTC:A	acceptor_gain	1.0000
5:149863264:TTC:T	acceptor_gain	1.0000
5:149863265:TC:T	acceptor_gain	1.0000
5:149863265:TCCTA:T	acceptor_loss	1.0000
5:149863266:CC:C	acceptor_gain	1.0000
5:149863267:C:CA	acceptor_loss	1.0000
5:149863267:C:CC	acceptor_gain	1.0000
5:149866250:TGGG:T	acceptor_gain	1.0000
5:149866259:A:C	acceptor_gain	1.0000
5:149867723:A:AC	donor_gain	1.0000
5:149867724:C:CC	donor_gain	1.0000
5:149883427:A:AC	donor_gain	1.0000
5:149883428:C:CC	donor_gain	1.0000
5:149883428:CATA:C	donor_gain	1.0000
5:149883428:CATAA:C	donor_gain	1.0000
5:149883432:A:C	donor_gain	1.0000
5:149883442:T:TA	donor_gain	1.0000
5:149884474:CCAA:C	donor_gain	1.0000
5:149884477:A:AC	donor_gain	1.0000
5:149884478:C:CC	donor_gain	1.0000
5:149884576:GGCT:G	acceptor_gain	1.0000
5:149884578:CT:C	acceptor_gain	1.0000
5:149884579:TC:T	acceptor_loss	1.0000
5:149884580:C:CC	acceptor_gain	1.0000
5:149884580:CTAAA:C	acceptor_loss	1.0000

AlphaMissense

5807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:149863198:C:A	W809C	1.000
5:149863198:C:G	W809C	1.000
5:149863200:A:G	W809R	1.000
5:149863200:A:T	W809R	1.000
5:149863208:C:G	R806P	1.000
5:149866177:A:T	V784D	1.000
5:149866185:G:C	C781W	1.000
5:149866186:C:A	C781F	1.000
5:149866186:C:T	C781Y	1.000
5:149866187:A:G	C781R	1.000
5:149866189:A:T	V780D	1.000
5:149866191:A:C	F779L	1.000
5:149866191:A:T	F779L	1.000
5:149866193:A:G	F779L	1.000
5:149866200:G:C	F776L	1.000
5:149866200:G:T	F776L	1.000
5:149866201:A:C	F776C	1.000
5:149866201:A:G	F776S	1.000
5:149866202:A:C	F776V	1.000
5:149866202:A:G	F776L	1.000
5:149866202:A:T	F776I	1.000
5:149866209:T:A	Q773H	1.000
5:149866209:T:G	Q773H	1.000
5:149866245:C:A	M761I	1.000
5:149866245:C:G	M761I	1.000
5:149866245:C:T	M761I	1.000
5:149867762:C:A	G746V	1.000
5:149867762:C:T	G746D	1.000
5:149867763:C:A	G746C	1.000
5:149867763:C:G	G746R	1.000

dbSNP variants (sampled 300 via entrez): RS1000032370 (5:149903157 A>G), RS1000110637 (5:149865846 T>C), RS1000112130 (5:149865042 C>A), RS1000138345 (5:149874283 TCCCCAAGTTA>T), RS1000168547 (5:149872269 A>G), RS1000176362 (5:149867349 G>A), RS1000210199 (5:149913687 C>T), RS1000221280 (5:149872024 C>G,T), RS1000283036 (5:149858937 G>A), RS1000294388 (5:149901984 C>G), RS1000362063 (5:149927686 A>G), RS1000369218 (5:149878557 G>A), RS1000409021 (5:149893358 G>T), RS1000412122 (5:149898830 A>C), RS1000461445 (5:149865294 C>T)

Disease associations

OMIM: gene MIM:180071 | disease phenotypes: MIM:613810, MIM:268000, MIM:276900, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 43	Definitive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
PDE6A-related retinopathy	Definitive	AR

Mondo (6): retinitis pigmentosa 43 (MONDO:0013437), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), PDE6A-related retinopathy (MONDO:0700224), Usher syndrome (MONDO:0019501), Leber congenital amaurosis (MONDO:0018998)

Orphanet (4): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Usher syndrome (Orphanet:886), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
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:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
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
HP:0008046	Abnormal retinal vascular morphology
HP:0011505	Cystoid macular edema
HP:0012426	Optic disc drusen

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095220 (SELECTIVITY GROUP), CHEMBL2097163 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3430880 (PROTEIN COMPLEX), CHEMBL3878 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 163,460 (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
CHEMBL1305	ANTAZOLINE	4	9,182
CHEMBL28079	ZAPRINAST	2	16,158
CHEMBL3109802	TBA-7371	2	51
CHEMBL2180408	JNJ-42396302	1	12

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 53 [PMID: 19631533]	Inhibition	8.01	pIC50

ChEMBL bioactivities

165 potent at pChembl≥5 of 176 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
8.33	IC50	4.7	nM	CHEMBL565305
8.13	IC50	7.4	nM	CHEMBL2180942
8.07	IC50	8.6	nM	CHEMBL584270
8.03	IC50	9.3	nM	CHEMBL566797
8.02	IC50	9.5	nM	SILDENAFIL
8.01	IC50	9.8	nM	CHEMBL567470
7.97	IC50	10.8	nM	CHEMBL569481
7.96	IC50	11	nM	VARDENAFIL
7.96	IC50	11	nM	CHEMBL5715931
7.95	IC50	11.3	nM	CHEMBL551052
7.86	IC50	13.8	nM	CHEMBL567447
7.83	IC50	14.7	nM	CHEMBL585918
7.82	IC50	15.2	nM	CHEMBL568839
7.82	IC50	15.3	nM	CHEMBL566367
7.82	IC50	15.1	nM	CHEMBL567471
7.82	IC50	15.3	nM	CHEMBL566820
7.79	IC50	16.1	nM	CHEMBL565306
7.75	IC50	17.7	nM	CHEMBL569492
7.75	IC50	17.9	nM	CHEMBL566375
7.63	IC50	23.6	nM	CHEMBL569045
7.63	IC50	23.2	nM	CHEMBL583854
7.61	IC50	24.6	nM	CHEMBL569264
7.60	IC50	25	nM	SILDENAFIL
7.58	IC50	26.3	nM	CHEMBL585327
7.52	IC50	30.1	nM	CHEMBL4062273
7.50	IC50	31.4	nM	CHEMBL567016
7.46	IC50	34.5	nM	CHEMBL569491
7.40	IC50	40	nM	SILDENAFIL
7.40	IC50	39.5	nM	CHEMBL566598
7.36	Ki	44	nM	THPP-1
7.34	IC50	45.5	nM	CHEMBL565308
7.30	Ki	50	nM	SILDENAFIL
7.30	IC50	49.7	nM	CHEMBL585015
7.29	IC50	51.8	nM	CHEMBL584056
7.25	IC50	55.9	nM	CHEMBL567445
7.24	IC50	58	nM	CHEMBL4099219
7.24	IC50	57.4	nM	CHEMBL584317
7.21	IC50	62	nM	CHEMBL213060
7.21	IC50	61.8	nM	CHEMBL551250

PubChem BioAssay actives

150 with measured affinity, of 311 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
7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0047	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
7-(6-methoxy-3-pyridinyl)-3-(oxolan-2-ylmethylamino)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0086	uM
3-(2-ethoxyethylamino)-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0093	uM
3-[(4-hydroxycyclohexyl)amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0098	uM
7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)-3-(pyridin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0108	uM
7-(6-methoxy-3-pyridinyl)-3-(2-morpholin-4-ylethylamino)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0113	uM
3-(3-hydroxypropylamino)-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0138	uM
7-(6-methoxy-3-pyridinyl)-3-[[2-(4-methylpiperazin-1-yl)-2-oxoethyl]amino]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0147	uM
3-[[(2R)-2-hydroxypropyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0151	uM
2-[[7-(6-methoxy-3-pyridinyl)-2-oxo-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-3-yl]amino]-N-methylacetamide	446782: Inhibition of PDE6	ic50	0.0152	uM
3-[[(2S)-2-hydroxypropyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0153	uM
3-[(4-hydroxycyclohexyl)amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0153	uM
7-(6-methoxy-3-pyridinyl)-3-[(2-morpholin-4-yl-2-oxoethyl)amino]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0161	uM
3-[[(2R)-1-hydroxypropan-2-yl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0177	uM
3-[[(2S)-1-hydroxypropan-2-yl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0179	uM
3-[[(2R)-1-hydroxybutan-2-yl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0232	uM
7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0236	uM
3-[[2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0246	uM
3-(2-hydroxyethylamino)-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0263	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
7-(6-methoxy-3-pyridinyl)-3-(oxan-4-ylmethylamino)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0314	uM
7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)-3-(pyridin-2-ylmethylamino)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0345	uM
7-(6-methoxy-3-pyridinyl)-3-[(2-oxo-2-pyrrolidin-1-ylethyl)amino]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0395	uM
2-[[7-(6-methoxy-3-pyridinyl)-2-oxo-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-3-yl]amino]acetic acid	446782: Inhibition of PDE6	ic50	0.0455	uM
3-[[(2R)-2-hydroxypropyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0497	uM
3-[[(2S)-2-hydroxypropyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0518	uM
3-[[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0559	uM
3-(2-ethoxyethylamino)-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0574	uM
3-(1,3-benzodioxol-5-ylmethyl)-1-(1,3-thiazol-2-yl)-2H-chromeno[2,3-c]pyrrol-9-one	1446365: Inhibition of PDE6A (484 to 817 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using [3H]cGMP or [3H]cAMP as substrate after 15 mins by liquid scintillation counting method	ic50	0.0580	uM
7-(6-methoxy-3-pyridinyl)-3-(2-morpholin-4-ylethylamino)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0618	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
3-[[(2R)-1-hydroxypropan-2-yl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0632	uM
3-[[(2S)-1-hydroxypropan-2-yl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0682	uM
1-(2-chlorophenyl)-6,8-dimethoxy-3-methylimidazo[5,1-c][1,2,4]benzotriazine	678635: Inhibition of PDE6	ic50	0.0732	uM
7-(6-methoxy-3-pyridinyl)-3-[[2-(4-methylpiperazin-1-yl)-2-oxoethyl]amino]-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0802	uM
2-[[7-(6-methoxy-3-pyridinyl)-2-oxo-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-3-yl]amino]-N,N-dimethylacetamide	446782: Inhibition of PDE6	ic50	0.0866	uM
2-[[7-(6-methoxy-3-pyridinyl)-2-oxo-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-3-yl]amino]acetamide	446782: Inhibition of PDE6	ic50	0.0866	uM
3-[[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446782: Inhibition of PDE6	ic50	0.0989	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Valproic Acid	increases methylation	1
Isotretinoin	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

69 unique, capped per target: 65 binding, 3 admet, 1 functional

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
CHEMBL5291859	Functional	Compound was evaluated for inhibition of human PDE6A in an in vitro cell free assay measured by scintillation proximity assay	A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs. — Nat Commun

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_UM39	FRIMOi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

234 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
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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)
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
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa