PDE6D

Summary

PDE6D (phosphodiesterase 6D, HGNC:8788) is a protein-coding gene on chromosome 2q37.1, encoding Retinal rod rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit delta (O43924). Promotes the release of prenylated target proteins from cellular membranes.

This gene encodes the delta subunit of rod-specific photoreceptor phosphodiesterase (PDE), a key enzyme in the phototransduction cascade. A similar protein in cow functions in solubilizing membrane-bound PDE. In addition to its role in the PDE complex, the encoded protein is thought to bind to prenyl groups of proteins to target them to subcellular organelles called cilia. Mutations in this gene are associated with Joubert syndrome-22. Alternative splicing results in multiple splice variants.

Source: NCBI Gene 5147 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 22 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 76 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 84
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002601

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8788
Approved symbol	PDE6D
Name	phosphodiesterase 6D
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	JBTS22
Ensembl gene	ENSG00000156973
Ensembl biotype	protein_coding
OMIM	602676
Entrez	5147

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000287600, ENST00000409772, ENST00000428104, ENST00000477748, ENST00000486044, ENST00000938376

RefSeq mRNA: 2 — MANE Select: NM_002601 NM_001291018, NM_002601

CCDS: CCDS33398, CCDS77538

Canonical transcript exons

ENST00000287600 — 5 exons

Exon	Start	End
ENSE00001029425	231738013	231738138
ENSE00001829481	231781065	231781282
ENSE00001872609	231732433	231733033
ENSE00003544048	231739100	231739188
ENSE00003784431	231737187	231737292

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 95.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3104 / max 54.2742, expressed in 1744 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34541	5.6110	1716
34540	0.5391	286
34542	0.1386	38
34543	0.0217	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.26	gold quality
right testis	UBERON:0004534	95.21	gold quality
testis	UBERON:0000473	93.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.91	gold quality
ventricular zone	UBERON:0003053	93.79	gold quality
cortical plate	UBERON:0005343	93.64	gold quality
spinal cord	UBERON:0002240	93.10	gold quality
ganglionic eminence	UBERON:0004023	92.78	gold quality
caudate nucleus	UBERON:0001873	92.38	gold quality
amygdala	UBERON:0001876	92.30	gold quality
putamen	UBERON:0001874	92.23	gold quality
prefrontal cortex	UBERON:0000451	91.91	gold quality
cingulate cortex	UBERON:0003027	91.67	gold quality
anterior cingulate cortex	UBERON:0009835	91.60	gold quality
monocyte	CL:0000576	91.49	gold quality
right adrenal gland cortex	UBERON:0035827	91.49	gold quality
nucleus accumbens	UBERON:0001882	91.39	gold quality
right adrenal gland	UBERON:0001233	91.32	gold quality
mononuclear cell	CL:0000842	91.13	gold quality
leukocyte	CL:0000738	91.00	gold quality
hypothalamus	UBERON:0001898	90.89	gold quality
left adrenal gland	UBERON:0001234	90.85	gold quality
right frontal lobe	UBERON:0002810	90.83	gold quality
sperm	CL:0000019	90.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.52	gold quality
left adrenal gland cortex	UBERON:0035825	90.46	gold quality
medial globus pallidus	UBERON:0002477	90.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.31	gold quality
substantia nigra	UBERON:0002038	90.18	gold quality
granulocyte	CL:0000094	90.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-5	no	2.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting PDE6D, 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-3924	100.00	72.09	2394
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-11181-3P	99.75	66.38	2205

Literature-anchored findings (GeneRIF, showing 9)

• Data show that PDEdelta activity augments K/Hras signalling by enriching Ras at the plasma membrane. (PMID:22179043)
• findings indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network that is involved in JBTS and NPHP but independent of the ones previously defined by NPHP and MKS proteins (PMID:23150559)
• RPGR is acting as a scaffold protein recruiting cargo-loaded PDE6D and Arl3 to release lipidated cargo into cilia. (PMID:23559067)
• Study identifies PDE6D as a novel Joubert syndrome gene and provides the first evidence of prenyl-binding-dependent trafficking in ciliopathies. (PMID:24166846)
• Studies indicate that the binding of UNC119 and PDE6D, to the lipid-modified ciliary cargo and the specific release of the cargo in the cilia by the ciliary small G-protein Arl3 in a GTP-dependent manner. (PMID:27911709)
• PDE6delta binds selectively to the C-terminus of RPGR and that this interaction is critical for RPGR’s localization to cilia. (PMID:28172980)
• The variant was confirmed by Sanger sequencing and found at the heterozygous state in both parents. A review of the literature pertaining to the role of PDE6D in Joubert syndrome is discussed. (PMID:30423442)
• Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects. (PMID:35422065)
• PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia. (PMID:36672247)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde6d	ENSDARG00000074892
mus_musculus	Pde6d	ENSMUSG00000026239
rattus_norvegicus	Pde6d	ENSRNOG00000018610
drosophila_melanogaster	PrBP	FBGN0032059
caenorhabditis_elegans		WBGENE00003966

Protein

Protein identifiers

Retinal rod rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit delta — O43924 (reviewed: O43924)

Alternative names: Protein p17

All UniProt accessions (4): O43924, B8ZZK5, C9IZ52, Q6IB24

UniProt curated annotations — full annotation on UniProt →

Function. Promotes the release of prenylated target proteins from cellular membranes. Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location. Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E. Required for RAB28 localization to the cone cell outer segments in the retina. Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.

Subunit / interactions. Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains (PDE6A and PDE6B) and two inhibitory chains (gamma); has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane. Interacts with prenylated GRK1 and GRK7. Interacts with prenylated Ras family members, including RAP2A and RAP2C. Interacts with prenylated RHEB and NRAS. Interacts with prenylated HRAS and KRAS. Interacts with RAB13 (prenylated form); dissociates RAB13 from membranes. Interacts with prenylated INPP5E. Interacts with RAB28 (prenylated form); the interaction promotes RAB28 delivery to the photoreceptor outer segments. Interacts with RPGR. Interacts with ARL2. Interacts with ARL3; the interaction occurs specifically with the GTP-bound form of ARL3. Interaction with ARL2 and ARL3 promotes release of farnesylated cargo proteins.

Subcellular location. Cytoplasm. Cytosol. Cytoplasmic vesicle membrane. Cytoskeleton. Cilium basal body.

Tissue specificity. Widely expressed. Detected in various tissues including spleen, prostate gland, testis, ovary, small intestine, colon, retina, and peripheral blood.

Disease relevance. Joubert syndrome 22 (JBTS22) [MIM:615665] A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PDE6D/unc-119 family.

RefSeq proteins (2): NP_001277947, NP_002592* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008015	PDED_dom	Domain
IPR014756	Ig_E-set	Homologous_superfamily
IPR017287	Rhodop-sen_GMP-Pdiesterase_dsu	Family
IPR037036	PDED_dom_sf	Homologous_superfamily

Pfam: PF05351

UniProt features (19 total): strand 9, helix 4, turn 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

40 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5ML3	X-RAY DIFFRACTION	1.4
4JV8	X-RAY DIFFRACTION	1.45
7Q9Q	X-RAY DIFFRACTION	1.45
7PAD	X-RAY DIFFRACTION	1.49
5ML2	X-RAY DIFFRACTION	1.6
9HMC	X-RAY DIFFRACTION	1.65
3T5G	X-RAY DIFFRACTION	1.7
4JVB	X-RAY DIFFRACTION	1.75
1KSH	X-RAY DIFFRACTION	1.8
9RP6	X-RAY DIFFRACTION	1.8
5F2U	X-RAY DIFFRACTION	1.85
7PAE	X-RAY DIFFRACTION	1.85
7Q9S	X-RAY DIFFRACTION	1.85
4JV6	X-RAY DIFFRACTION	1.87
5ML6	X-RAY DIFFRACTION	1.87
4JHP	X-RAY DIFFRACTION	1.9
5TAR	X-RAY DIFFRACTION	1.9
9RP7	X-RAY DIFFRACTION	1.9
5X72	X-RAY DIFFRACTION	1.95
7QF9	X-RAY DIFFRACTION	1.95
5YAV	X-RAY DIFFRACTION	1.99
5TB5	X-RAY DIFFRACTION	2
5YAW	X-RAY DIFFRACTION	2.03
7PAC	X-RAY DIFFRACTION	2.05
3T5I	X-RAY DIFFRACTION	2.1
5E8F	X-RAY DIFFRACTION	2.1
5NAL	X-RAY DIFFRACTION	2.2
7Q9U	X-RAY DIFFRACTION	2.24
5X74	X-RAY DIFFRACTION	2.25
1KSG	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43924-F1	96.40	0.94

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5624958	ARL13B-mediated ciliary trafficking of INPP5E
R-HSA-9648002	RAS processing

MSigDB gene sets: 413 (showing top): RRAGTTGT_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AP2_Q3, GOMF_GTPASE_BINDING, EFC_Q6, MODULE_205, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, ATTACAT_MIR3803P, KEGG_PURINE_METABOLISM, GOBP_SENSORY_PERCEPTION, MORF_AATF, DANG_BOUND_BY_MYC, CTAWWWATA_RSRFC4_Q2

GO Biological Process (2): visual perception (GO:0007601), sensory perception of light stimulus (GO:0050953)

GO Molecular Function (3): GTPase inhibitor activity (GO:0005095), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1
RAF/MAP kinase cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
sensory perception of light stimulus	1
sensory perception	1
GTPase activity	1
enzyme inhibitor activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1114 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE6D	ALDH7A1	P49419	817
PDE6D	UNC119	Q13432	799
PDE6D	ARL13B	Q3SXY8	789
PDE6D	RPGR	Q92834	733
PDE6D	ARL3	P36405	727
PDE6D	RCC1L	Q96I51	722
PDE6D	GRK1	Q15835	674
PDE6D	PDE6A	P16499	670
PDE6D	RPGRIP1L	Q68CZ1	669
PDE6D	RPGRIP1	Q96KN7	667
PDE6D	PDE6C	P51160	646
PDE6D	CEP164	Q9UPV0	638
PDE6D	RAB13	P51153	636
PDE6D	UNC119B	A6NIH7	633
PDE6D	CEP41	Q9BYV8	610

IntAct

97 interactions, top by confidence:

A	B	Type	Score
ARL2	PDE6D	psi-mi:“MI:0915”(physical association)	0.960
PDE6D	ARL2	psi-mi:“MI:0915”(physical association)	0.960
ARL2	PDE6D	psi-mi:“MI:0407”(direct interaction)	0.960
PDE6D	ARL2	psi-mi:“MI:0407”(direct interaction)	0.960
PDE6D	ARL3	psi-mi:“MI:0914”(association)	0.920
PDE6D	ARL3	psi-mi:“MI:0915”(physical association)	0.920
PDE6D	ARL3	psi-mi:“MI:0407”(direct interaction)	0.920
RPGR	PDE6D	psi-mi:“MI:0407”(direct interaction)	0.860
PDE6D	RPGR	psi-mi:“MI:0407”(direct interaction)	0.860
PDE6D	RPGR	psi-mi:“MI:0915”(physical association)	0.860
PDE6D	ARL16	psi-mi:“MI:0915”(physical association)	0.790
ARL16	PDE6D	psi-mi:“MI:0915”(physical association)	0.790

BioGRID (96): PDE6D (Two-hybrid), ARL16 (Two-hybrid), PDE6D (Affinity Capture-MS), RHOB (Two-hybrid), RHOA (Two-hybrid), RAD23A (Two-hybrid), PDE6D (Two-hybrid), RAP1A (Two-hybrid), RAP2B (Two-hybrid), PDE6D (Two-hybrid), PDE6D (Two-hybrid), PDE6D (Affinity Capture-MS), PDE6D (Affinity Capture-MS), PDE6D (Affinity Capture-MS), PDE6D (Affinity Capture-MS)

ESM2 similar proteins: A0A5K1K8Y8, A8BCK6, A8N3G7, A8NSH0, A8NSH3, B0WS18, B3N7D5, B4GJ61, B4HYQ2, B4JDZ5, B4KG03, B4LSE6, B4N7S9, B4NXG9, B4Q785, B7G620, C0HLX7, C0HM19, H2KZU7, O43924, O55057, O61931, P18517, P20302, P28958, P34607, P52440, P84399, P86860, Q06100, Q09605, Q17FF6, Q18268, Q197B9, Q206Z5, Q20952, Q23652, Q24592, Q29JT7, Q3E841

Diamond homologs: B0WS18, B3N7D5, B4GJ61, B4HYQ2, B4JDZ5, B4KG03, B4LSE6, B4N7S9, B4NXG9, B4Q785, O43924, O55057, Q17FF6, Q18268, Q29JT7, Q7PZ66, Q95142, Q9VLJ0, Q9XT54, Q8C4B4, A6NIH7, O19177, Q10658, Q13432, Q17297, Q3SYR2, Q62885, Q66JA9, Q6INE2, Q90Z08, Q9XYQ2, Q9Z2R6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	27
Likely benign	35
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
100773	NM_002601.4(PDE6D):c.140-1G>A	Pathogenic
1382726	NM_002601.4(PDE6D):c.114del (p.Ser39fs)	Pathogenic
1414071	NM_002601.4(PDE6D):c.66del (p.Arg23fs)	Pathogenic
1683781	NM_002601.4(PDE6D):c.46A>T (p.Lys16Ter)	Pathogenic
2001656	NM_002601.4(PDE6D):c.342del (p.Glu114fs)	Pathogenic
2181645	NM_002601.4(PDE6D):c.181C>T (p.Arg61Ter)	Pathogenic
2424497	NC_000002.11:g.(?232645755)(232645824_?)del	Pathogenic
917951	NM_002601.4(PDE6D):c.257del (p.Cys86fs)	Likely pathogenic

SpliceAI

1207 predictions. Top by Δscore:

Variant	Effect	Δscore
2:231781087:C:CA	donor_gain	1.0000
2:231781101:T:TA	donor_gain	1.0000
2:231733034:C:CC	acceptor_gain	0.9900
2:231737185:A:AC	donor_gain	0.9900
2:231737186:C:CC	donor_gain	0.9900
2:231737288:CCATT:C	acceptor_gain	0.9900
2:231737289:CATTC:C	acceptor_gain	0.9900
2:231738135:CGGG:C	acceptor_gain	0.9900
2:231739198:TATGA:T	acceptor_gain	0.9900
2:231781052:C:CA	donor_gain	0.9900
2:231781063:A:AC	donor_gain	0.9900
2:231781064:C:CC	donor_gain	0.9900
2:231781882:TGGTA:T	donor_loss	0.9900
2:231781883:GGT:G	donor_loss	0.9900
2:231781884:G:GC	donor_loss	0.9900
2:231781884:G:GG	donor_gain	0.9900
2:231781885:T:A	donor_loss	0.9900
2:231733030:CCCA:C	acceptor_gain	0.9800
2:231733031:CCA:C	acceptor_gain	0.9800
2:231733031:CCAC:C	acceptor_gain	0.9800
2:231733032:CAC:C	acceptor_gain	0.9800
2:231739203:C:CC	acceptor_gain	0.9800
2:231781064:CA:C	donor_gain	0.9800
2:231781146:CT:C	donor_gain	0.9800
2:231733032:CA:C	acceptor_gain	0.9700
2:231737293:C:CC	acceptor_gain	0.9700
2:231781064:CAG:C	donor_gain	0.9700
2:231781102:C:A	donor_gain	0.9700
2:231781059:GGATA:G	donor_loss	0.9600
2:231781060:GATAC:G	donor_loss	0.9600

AlphaMissense

992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:231737239:A:G	S107P	1.000
2:231737245:A:G	W105R	1.000
2:231737245:A:T	W105R	1.000
2:231737268:A:T	V97E	1.000
2:231738051:A:G	L76P	1.000
2:231738083:A:C	F65L	1.000
2:231738083:A:T	F65L	1.000
2:231738084:A:G	F65S	1.000
2:231738085:A:G	F65L	1.000
2:231738102:A:T	V59E	1.000
2:231738117:A:G	L54P	1.000
2:231738132:A:T	V49D	1.000
2:231739143:C:A	W32C	1.000
2:231739143:C:G	W32C	1.000
2:231739145:A:G	W32R	1.000
2:231739145:A:T	W32R	1.000
2:231739174:A:G	L22P	1.000
2:231732978:A:G	S143P	0.999
2:231733006:A:C	F133L	0.999
2:231733006:A:T	F133L	0.999
2:231733008:A:G	F133L	0.999
2:231733019:A:T	I129K	0.999
2:231733031:C:A	G125V	0.999
2:231733032:C:A	G125W	0.999
2:231737249:A:C	N103K	0.999
2:231737249:A:T	N103K	0.999
2:231737256:G:A	S101F	0.999
2:231737257:A:G	S101P	0.999
2:231737274:C:A	G95V	0.999
2:231737276:A:C	F94L	0.999

dbSNP variants (sampled 300 via entrez): RS1000034235 (2:231760644 T>C), RS1000084577 (2:231779031 A>T), RS1000150134 (2:231777694 A>C), RS1000185232 (2:231771861 G>T), RS1000300564 (2:231738686 C>T), RS1000343071 (2:231765185 A>T), RS1000462359 (2:231733742 T>C), RS1000476095 (2:231778763 T>C), RS1000487883 (2:231758327 A>C), RS1000562132 (2:231773911 A>G), RS1000569828 (2:231754664 G>A), RS1000633445 (2:231762283 T>C,G), RS1000737295 (2:231774224 T>C), RS1000744007 (2:231748018 C>T), RS1000772088 (2:231767269 T>C)

Disease associations

OMIM: gene MIM:602676 | disease phenotypes: MIM:615665

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 22	Strong	Autosomal recessive
orofaciodigital syndrome type 6	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Moderate	AR

Mondo (2): Joubert syndrome 22 (MONDO:0014297), orofaciodigital syndrome type 6 (MONDO:0010176)

Orphanet (1): Orofaciodigital syndrome type 6 (Orphanet:2754)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000089	Renal hypoplasia
HP:0000104	Renal agenesis
HP:0000175	Cleft palate
HP:0000180	Lobulated tongue
HP:0000190	Abnormal oral frenulum morphology
HP:0000199	Tongue nodules
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000550	Undetectable electroretinogram
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000175_5	Height	1.000000e-06
GCST001959_2	Eating disorders (purging via substances)	7.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536531	Orofaciodigital syndrome 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2095220 (SELECTIVITY GROUP), CHEMBL2097163 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3860 (SINGLE PROTEIN), CHEMBL4523623 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630727 (PROTEIN-PROTEIN INTERACTION), CHEMBL5482984 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 281,797 (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
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1496	ROSUVASTATIN	4	41,471
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)

Binding affinities (BindingDB)

12 measured of 13 human assays (13 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5092661	KI	8.6 nM
CHEMBL5084153	KI	9.3 nM
CHEMBL5089219	KI	14 nM
CHEMBL5094121	KI	26 nM
CHEMBL5077941	KI	29 nM
CHEMBL5086138	KI	39 nM
CHEMBL5079726	KI	41 nM
CHEMBL5083136	KI	44 nM
CHEMBL5087129	KI	45 nM
CHEMBL5072868	KI	49 nM
CHEMBL5084808	KI	132 nM
CHEMBL5082602	KI	147 nM

ChEMBL bioactivities

307 potent at pChembl≥5 of 316 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.11	Kd	0.077	nM	CHEMBL3286930
10.00	IC50	0.1	nM	CHEMBL5081214
9.96	Kd	0.11	nM	CHEMBL4472979
9.90	IC50	0.1259	nM	CHEMBL5080391
9.80	IC50	0.1585	nM	CHEMBL5087564
9.69	Kd	0.203	nM	CHEMBL4472979
9.60	IC50	0.2512	nM	CHEMBL5094110
9.55	Kd	0.28	nM	CHEMBL6172356
9.54	Kd	0.29	nM	CHEMBL6176693
9.52	Kd	0.3	nM	CHEMBL5594211
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.49	Kd	0.32	nM	CHEMBL6174102
9.46	Kd	0.35	nM	CHEMBL6152045
9.39	Kd	0.41	nM	CHEMBL6175400
9.30	IC50	0.5	nM	SILDENAFIL
9.22	Kd	0.6	nM	CHEMBL4061005
9.22	Kd	0.6	nM	CHEMBL6169152
9.17	Kd	0.67	nM	CHEMBL6168427
9.09	Kd	0.82	nM	CHEMBL6172236
9.00	IC50	1	nM	VARDENAFIL
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742
8.96	Kd	1.1	nM	CHEMBL3286929
8.89	Kd	1.3	nM	CHEMBL5595916
8.82	Kd	1.5	nM	CHEMBL5595364
8.80	Kd	1.6	nM	CHEMBL5592316
8.78	Kd	1.65	nM	CHEMBL6174703
8.70	Kd	2	nM	CHEMBL4061005
8.66	IC50	2.2	nM	CHEMBL2414311
8.66	Kd	2.2	nM	CHEMBL1387422
8.64	Kd	2.3	nM	CHEMBL4090695
8.58	Kd	2.64	nM	CHEMBL6160928
8.58	Kd	2.65	nM	CHEMBL6176765
8.42	Kd	3.8	nM	CHEMBL1387422
8.40	Kd	4	nM	CHEMBL4061982
8.40	Kd	4	nM	CHEMBL4082888
8.40	Kd	4	nM	CHEMBL5595347
8.35	Kd	4.5	nM	CHEMBL4073926
8.35	Kd	4.5	nM	CHEMBL5591954
8.29	Kd	5.16	nM	CHEMBL4061005
8.22	Kd	6	nM	CHEMBL3286915
8.22	Kd	6	nM	CHEMBL5592414
8.22	Kd	6	nM	CHEMBL5583878
8.22	Kd	6	nM	CHEMBL5592494
8.15	Kd	7	nM	CHEMBL3286909
8.15	Kd	7	nM	CHEMBL3286914
8.15	Kd	7	nM	CHEMBL3286917
8.14	Kd	7.2	nM	CHEMBL5591087
8.13	IC50	7.4	nM	CHEMBL2180942

PubChem BioAssay actives

295 with measured affinity, of 563 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
4-N-[(4-chlorophenyl)methyl]-4-N-cyclopentyl-1-N-[[2-(methylamino)pyrimidin-4-yl]methyl]-1-N-(piperidin-4-ylmethyl)benzene-1,4-disulfonamide	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	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
[(2S)-2-(2-phenylbenzimidazol-1-yl)-2-piperidin-4-ylethyl] 1-(1-benzylbenzimidazol-2-yl)piperidine-4-carboxylate	1154662: Binding affinity to PDE-delta (unknown origin) by SPR analysis	kd	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
methyl 4-[4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]piperidin-1-yl]-2-nitrobenzoate	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	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]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
3-[1-[3-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]propanoyl]piperidin-4-yl]-2-(2-fluorophenyl)-1,2-dihydroquinazolin-4-one	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0006	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
1-benzyl-2-[4-[(2S)-2-(2-phenylbenzimidazol-1-yl)-2-piperidin-4-ylethoxy]phenyl]benzimidazole	1154661: Binding affinity to PDE-delta (unknown origin) by time-resolved fluorescence anisotropic analysis	kd	0.0011	uM
methyl 4-[4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]piperidin-1-yl]benzoate	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0013	uM
N-[7-[[1-(4-bromo-2-nitrophenyl)piperidin-4-yl]methyl-ethylamino]-7-oxoheptyl]-4-fluoro-N-propan-2-ylbenzamide	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0015	uM
methyl 3-amino-4-[4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]piperidin-1-yl]benzoate	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0016	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
4-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]-N-(2-phenylpropyl)butanamide	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0022	uM
(2R)-2-(2-fluorophenyl)-3-[2-[4-[(2R)-2-(2-fluorophenyl)-4-oxo-1,2-dihydroquinazolin-3-yl]piperidin-1-yl]ethyl]-1,2-dihydroquinazolin-4-one	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0023	uM
2-(2-fluorophenyl)-3-[6-[2-(2-fluorophenyl)-4-oxo-1,2-dihydroquinazolin-3-yl]hexyl]-1,2-dihydroquinazolin-4-one	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0040	uM
3-[1-[3-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]propyl]piperidin-4-yl]-2-(2-fluorophenyl)-1,2-dihydroquinazolin-4-one	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0040	uM
N-cyclopentyl-N-[7-[ethyl-[[2-(methylamino)pyrimidin-4-yl]methyl]amino]-7-oxoheptyl]-4-fluorobenzamide	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0040	uM
6-fluoro-2-(2-fluorophenyl)-3-[2-[4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]phenoxy]ethyl]-1,2-dihydroquinazolin-4-one	1455769: Inhibition of atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0045	uM
4-[4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]piperidin-1-yl]-2-nitrobenzoic acid	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0045	uM
N-[7-[ethyl-[[2-(methylamino)pyrimidin-4-yl]methyl]amino]-7-oxoheptyl]-4-fluoro-N-propan-2-ylbenzamide	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0060	uM
methyl 4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]benzoate	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0060	uM
2-amino-4-[4-[[ethyl-[7-[(4-fluorobenzoyl)-propan-2-ylamino]heptanoyl]amino]methyl]piperidin-1-yl]benzoic acid	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0060	uM
2-(2-methylbenzimidazol-1-yl)ethyl 1-(1-benzylbenzimidazol-2-yl)piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0060	uM
[(2S)-2-(2-phenylbenzimidazol-1-yl)-2-piperidin-4-ylethyl] 1-[1-(thiophen-3-ylmethyl)benzimidazol-2-yl]piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0070	uM
2-(2-phenylimidazol-1-yl)ethyl 1-(1-benzylbenzimidazol-2-yl)piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0070	uM
1-benzyl-2-[4-[2-(2-phenylimidazol-1-yl)ethoxy]phenyl]benzimidazole	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0070	uM
7-[[4-benzyl-5-(2-methylpropyl)-1,2,4-triazol-3-yl]sulfanyl]-N-ethyl-N-[[2-(methylamino)pyrimidin-4-yl]methyl]heptanamide	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0072	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-(2-fluorophenyl)-3-[5-[2-(2-fluorophenyl)-4-oxo-1,2-dihydroquinazolin-3-yl]pentyl]-1,2-dihydroquinazolin-4-one	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0080	uM
4-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]-N-[8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]amino]octyl]butanamide	1658930: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0080	uM
[(2S)-2-piperidin-4-yl-2-(2-propan-2-ylbenzimidazol-1-yl)ethyl] 1-[1-(thiophen-3-ylmethyl)benzimidazol-2-yl]piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0080	uM
N-(1-adamantylmethyl)-N’-[4-[2-[4-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]butanoylamino]ethyl]phenyl]pentanediamide	1819699: Binding affinity to PDE delta (unknown origin) assessed as dissociation constant measured after 2 hrs by fluorescence polarization assay	ki	0.0086	uM
2-(2-fluorophenyl)-3-[7-[2-(2-fluorophenyl)-4-oxo-1,2-dihydroquinazolin-3-yl]heptyl]-1,2-dihydroquinazolin-4-one	1475929: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0090	uM
2-(2-fluorophenyl)-3-[2-[4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]phenoxy]ethyl]-1,2-dihydroquinazolin-4-one	1455769: Inhibition of atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0090	uM
4-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]-N-[8-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]octyl]butanamide	1658930: Inhibition of Atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0090	uM
N-cyclopentyl-4-fluoro-N-[7-[[2-(methylamino)pyrimidin-4-yl]methyl-(piperidin-4-ylmethyl)amino]-7-oxoheptyl]benzamide	2115757: Displacement of fluorescein-labeled Atorvastatin from N-terminal His6 tagged human recombinant PDE6D extracted from Escherichia coli BL21 star (DE3) pLysS assessed as dissociation constant by fluorescence polarization assay	kd	0.0090	uM
[2-(2-phenylbenzimidazol-1-yl)-2-piperidin-4-ylethyl] 1-[1-(thiophen-3-ylmethyl)benzimidazol-2-yl]piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0090	uM
[(2S)-2-(2-ethylbenzimidazol-1-yl)-2-piperidin-4-ylethyl] 1-[1-(thiophen-3-ylmethyl)benzimidazol-2-yl]piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0090	uM
2-(2-fluorophenyl)-6-methyl-3-[2-[4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]phenoxy]ethyl]-1,2-dihydroquinazolin-4-one	1455769: Inhibition of atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0093	uM
N-(1-adamantylmethyl)-4-[3,4-dimethyl-2-(4-methylphenyl)-7-oxopyrazolo[3,4-d]pyridazin-6-yl]butanamide	1819699: Binding affinity to PDE delta (unknown origin) assessed as dissociation constant measured after 2 hrs by fluorescence polarization assay	ki	0.0093	uM
4-[3,4-dimethyl-2-(4-methylphenyl)-7H-pyrazolo[3,4-d]pyridazin-6-yl]-N-(2-phenylpropyl)butanamide	2005778: Binding affinity to PDEdelta (unknown origin) assessed as dissociation constant incubated for overnight by fluorescence polarization assay	kd	0.0093	uM
2-(2-fluorophenyl)-7-methoxy-3-[2-[4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]phenoxy]ethyl]-1,2-dihydroquinazolin-4-one	1455769: Inhibition of atrovastatin-PEG3-FITC binding to PDEdelta (unknown origin) incubated for 60 mins by fluorescence anisotropy assay	kd	0.0098	uM
[2-(2-phenylbenzimidazol-1-yl)-2-piperidin-4-ylethyl] 1-(1-benzylbenzimidazol-2-yl)piperidine-4-carboxylate	1154659: Binding affinity to His6-tagged PDE-delta (unknown origin) measured every 3 mins by fluorescence polarization assay	kd	0.0100	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	4
sodium arsenite	increases expression, affects expression	2
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

147 unique, capped per target: 145 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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC68	HAP1 PDE6D (-) 1	Cancer cell line	Male
CVCL_XR47	HAP1 PDE6D (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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