PRKD1

Summary

PRKD1 (protein kinase D1, HGNC:9407) is a protein-coding gene on chromosome 14q12, encoding Serine/threonine-protein kinase D1 (Q15139). Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kapp…. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion.

Source: NCBI Gene 5587 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant polycystic kidney disease (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 73
• Clinical variants (ClinVar): 7,269 total — 1553 pathogenic, 499 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes — 26 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9407
Approved symbol	PRKD1
Name	protein kinase D1
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	PKD1, PKCM, PKD, PKC-mu
Ensembl gene	ENSG00000184304
Ensembl biotype	protein_coding
OMIM	605435
Entrez	5587

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 4 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000331968, ENST00000415220, ENST00000468370, ENST00000490795, ENST00000546371, ENST00000549503, ENST00000551644, ENST00000616995, ENST00000651571, ENST00000651616, ENST00000691338, ENST00000691517

RefSeq mRNA: 3 — MANE Select: NM_002742 NM_001330069, NM_001348390, NM_002742

CCDS: CCDS81796, CCDS9637

Canonical transcript exons

ENST00000331968 — 18 exons

Exon	Start	End
ENSE00001293875	29629041	29629093
ENSE00001294844	29624152	29624258
ENSE00001301698	29578275	29578360
ENSE00001302896	29630742	29631021
ENSE00001307947	29636290	29636494
ENSE00001313496	29626484	29626556
ENSE00001315972	29599656	29599817
ENSE00001321203	29725536	29725674
ENSE00001323321	29632869	29632946
ENSE00001326847	29597491	29597758
ENSE00001525893	29927249	29927847
ENSE00001632519	29634418	29634541
ENSE00001721247	29599027	29599125
ENSE00001759247	29666077	29666208
ENSE00003612005	29638489	29638566
ENSE00003639700	29663699	29663859
ENSE00003694211	29638694	29638904
ENSE00003899353	29576479	29577456

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 91.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0441 / max 85.0508, expressed in 1306 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142712	5.1090	1225
142710	1.4943	741
142711	0.2559	145
142709	0.1849	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	91.73	gold quality
seminal vesicle	UBERON:0000998	89.29	gold quality
thoracic aorta	UBERON:0001515	87.13	gold quality
ascending aorta	UBERON:0001496	87.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.46	gold quality
adrenal tissue	UBERON:0018303	86.30	gold quality
saphenous vein	UBERON:0007318	86.27	gold quality
descending thoracic aorta	UBERON:0002345	86.25	gold quality
aorta	UBERON:0000947	86.24	gold quality
right coronary artery	UBERON:0001625	85.84	gold quality
popliteal artery	UBERON:0002250	85.67	gold quality
prostate gland	UBERON:0002367	85.66	gold quality
tibial artery	UBERON:0007610	85.66	gold quality
renal medulla	UBERON:0000362	85.43	gold quality
stromal cell of endometrium	CL:0002255	85.04	gold quality
parietal pleura	UBERON:0002400	85.01	gold quality
left coronary artery	UBERON:0001626	84.97	gold quality
blood vessel layer	UBERON:0004797	84.86	gold quality
metanephros	UBERON:0000081	84.79	gold quality
ganglionic eminence	UBERON:0004023	84.72	gold quality
coronary artery	UBERON:0001621	84.24	gold quality
metanephros cortex	UBERON:0010533	84.13	gold quality
renal glomerulus	UBERON:0000074	83.71	gold quality
tibial nerve	UBERON:0001323	83.63	gold quality
testis	UBERON:0000473	83.61	gold quality
right testis	UBERON:0004534	83.60	gold quality
ovary	UBERON:0000992	83.57	gold quality
left ovary	UBERON:0002119	83.51	gold quality
pleura	UBERON:0000977	83.42	gold quality
left testis	UBERON:0004533	83.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	3082.97
E-GEOD-131882	yes	2734.86
E-ENAD-27	yes	105.76
E-ANND-3	yes	9.34
E-GEOD-99795	no	370.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

77 targeting PRKD1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Involvement of protein kinase D in Fc gamma-receptor activation of the NADPH oxidase in neutrophils (PMID:11903052)
• REVIEW: multifunctional role of PKD in processes such as cell proliferation, apoptosis, immune cell regulation, tumor cell invasion and regulation of Golgi vesicle fission. (PMID:11978539)
• study shows that PKD is rapidly activated by a wide variety of platelet agonists through a PKC-dependent pathway; activation of PKD enables phosphorylation of a distinct set of substrates to those targeted by PKC in platelets (PMID:12393506)
• This protein is associated with the COP9 signalosome. (PMID:12628923)
• PKD has a tyrosine phosphorylation-dependent activation, an event which contributes to the release of the autoinhibitory PKD PH domain leading to kinase activation and downstream responses (PMID:12637538)
• Data suggest that epidermal growth factor (EGF) stimulated c-Jun N-terminal kinase phosphorylation of c-Jun is uncoupled from protein kinase D suppression in cancer cells. (PMID:12646240)
• PKCmu activation is associated with a unique signaling pathway coupling TCR ligation with T cell proliferation. (PMID:12778467)
• Results demonstrate down regulation of protein kinase C mu at transcription and translational level, respectively, in AI C4-2 cells compared to its parental androgen dependent (AD) LNCaP prostate cancer cells. (PMID:12859948)
• PKCmu kinase domain binds to metallothionein 2A and may have a role in prostate cancer (PMID:14550308)
• protein kinase C mu has a role in calpain-mediated proteolysis for arachidonic acid-stimulated adhesion of tumor cells to collagen type IV (PMID:14607845)
• specificity of different PKD isoforms in regulating protein trafficking from the trans-Golgi network (PMID:14743217)
• Data show that activation of protein kinase D in response to oxidative stress requires two sequential signaling events, mediated by protein kinase Cdelta (PMID:15024053)
• Doxorubicin-mediated apoptosis induces activation of PKD1 through a novel mechanism involving the caspase-mediated proteolysis (PMID:15093611)
• PKD activation plays a central role in NT peptide secretion; upstream regulators of PKD include PKC-alpha and -delta and Rho/ROK (PMID:15123666)
• Ser(82) in the human heat shock protein Hsp27 is a novel substrate for PKD (PMID:15728188)
• PKD is a critical mediator in H2O2- but not TNF-induced ASK1-JNK signaling (PMID:15755722)
• PRKC-dependent PRKD1 activation modulates ERK signal pathway and endothelial cell proliferation by vascular endothelial growth factor A. (PMID:16006559)
• Protein kinase D-mediated MnSOD expression promotes increased survival of cells upon release of mitochondrial reactive oxygen species (PMID:16166634)
• PKD1 stimulates GAL4-CREB-mediated transcription in a Ser-133-dependent manner, activates CRE-responsive promoters (PMID:17389598)
• Phosphorylation of TLR5 by PKD may be one of the proximal elements in the cellular response to flagellin, and that this event contributes to p38 MAPK activation and production of inflammatory cytokines in epithelial cells. (PMID:17442957)
• Fission of transport carriers at the trans-Golgi network is dependent on specifically PLCbeta3, which is necessary to activate PKCeta and PKD in that Golgi compartment, via diacylglycerol production. (PMID:17492941)
• Neurotensin induces a striking increase in Hsp27 phosphorylation on Ser-82 in PANC-1 cells through convergent p38 MAPK, PKD, and PKD2 signaling. (PMID:17570131)
• Regulation of secretory transport by PKD-mediated phosphorylation of CERT is reported. (PMID:17591919)
• PKD is a physiologically relevant enzyme for SPHK2 phosphorylation, which leads to its nuclear export for subsequent cellular signaling. (PMID:17635916)
• these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress. (PMID:17703233)
• Data suggest that PKD1 phosphorylation at Tyr95 generates a binding motif for PKCdelta, and that oxidative stress-mediated PKCdelta/PKD interaction results in PKD1 activation loop phosphorylation and activation. (PMID:17804414)
• functional significance of combined dysregulation of PKD1 and E-cadherin in prostate cancer; their effect on cell growth is mediated by beta-catenin. (PMID:17979146)
• review: novel functions for PKD-mediated pathways in the heart and the circulation. (PMID:18239146)
• antidifferentiative role of PRKD1 in normal human keratinocytes, contrary to the prodiferentiative role of PRKD1 in human hTert keratinocytes (PMID:18259765)
• Protein kinase D-HDAC5 pathway plays an important role in VEGF regulation of gene transcription and angiogenesis (PMID:18332134)
• These findings identify a novel pathway for vascular endothelial growth factor-induced HSP27 serine 82 phosphorylation via PKC-mediated PKD activation and direct phosphorylation of HSP27 by PKD. (PMID:18440775)
• These data demonstrate for the first time that PKD1 can influence AR function in prostate cancer cells. (PMID:18602367)
• identify PKD1 as a key signaling modulator in TLR9-mediated macrophage activation (PMID:18641342)
• PKD activation is induced by DGKzeta, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells. (PMID:18694729)
• the PKD serine/threonine kinase is one of the signaling molecules through which integrin-mediated cell attachment controls Bit1 activity and anoikis (PMID:18703509)
• CID755673 inhibited the known biological actions of PKD1 (PMID:18829454)
• findings show protein kinase D phosphorylates Par-1b on S400 to positively regulate 14-3-3 binding and to negatively regulate membrane association (PMID:19011111)
• exposes a novel role for Ser916 and/or Ser748 autophosphorylation to terminate the cellular PKD1 signaling response (PMID:19029298)
• After disruption of cell-cell contacts, PKD1 relayed RhoA activation to the induction of the transcription factor NF-kappaB. (PMID:19173301)
• Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokines in endothelial cells. (PMID:19176759)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkd1	ENSDARG00000075949
mus_musculus	Prkd1	ENSMUSG00000002688
rattus_norvegicus	Prkd1	ENSRNOG00000004165
drosophila_melanogaster	PKD	FBGN0038603
caenorhabditis_elegans		WBGENE00012019
caenorhabditis_elegans	dkf-1	WBGENE00012352

Paralogs (2): PRKD2 (ENSG00000105287), PRKD3 (ENSG00000115825)

Protein

Protein identifiers

Serine/threonine-protein kinase D1 — Q15139 (reviewed: Q15139)

Alternative names: Protein kinase C mu type, Protein kinase D, nPKC-D1, nPKC-mu

All UniProt accessions (7): A0A494C0Q1, A0A494C196, F8VZ98, F8WBA3, Q15139, H0YHL5, H0YHS9

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells. Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection.

Subunit / interactions. Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with MAPK13. Interacts with DAPK1 in an oxidative stress-regulated manner. Interacts with USP28; the interaction induces phosphorylation of USP28 and activated KRAS-mediated stabilization of ZNF304. Interacts with AKAP13 (via C-terminal domain).

Subcellular location. Cytoplasm. Cell membrane. Golgi apparatus. trans-Golgi network.

Post-translational modifications. Phosphorylated at Ser-397 and Ser-401 by MAPK13 during regulation of insulin secretion in pancreatic beta cells. Phosphorylated by DAPK1. Phosphorylated at Tyr-95 and by ABL at Tyr-463, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-738/Ser-742 by PKRD. Phosphorylated on Ser-910 upon S.enterica infection in macrophages.

Disease relevance. Congenital heart defects and ectodermal dysplasia (CHDED) [MIM:617364] An autosomal dominant syndrome characterized by atrial and/or ventricular septal congenital heart defects and variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth. Patients manifest developmental disabilities ranging from motor delay and delayed speech to global developmental retardation. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-742 and phosphorylation of Ser-738 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-463 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress.

Induction. Up-regulated by the intestine-specific transcription factor CDX1 in an activated KRAS-dependent manner in colorectal cancer (CRC) cells.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.

RefSeq proteins (3): NP_001316998, NP_001335319, NP_002733* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015727	Protein_Kinase_C_mu-related	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020454	DAG/PE-bd	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR057764	Ubiquitin_PRKD1-3_N	Domain

Pfam: PF00069, PF00130, PF00169, PF25525

Enzyme classification (BRENDA):

• EC 2.7.11.13 — protein kinase C (BRENDA: 25 organisms, 203 substrates, 258 inhibitors, 20 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FKKQGSFAKKK	0.0166–0.0599	10
ATP	0.0001–0.0828	4
N6-PHENYL-ATP	0.0124	1
S6-(229-239) PEPTIDE	0.0036	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (49 total): modified residue 18, sequence variant 11, mutagenesis site 9, domain 2, zinc finger region 2, sequence conflict 2, binding site 2, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15139-F1	68.99	0.25

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): 706 (proton acceptor)

Ligand- & substrate-binding residues (2): 589–597; 612

Post-translational modifications (18): 205, 208, 219, 223, 345, 397, 401, 432, 448, 463, 473, 502, 548, 738, 742, 749, 910, 95

Mutagenesis-validated functional residues (9):

Position	Phenotype
157	increase in ability to bind phorbol ester, loss of ability to bind dag.
281	no effect on ability to bind phorbol ester, slight increase in ability to bind dag.
432	decreased phosphorylation level when coexpressed with src in hela cells. unchanged phosphorylation level when coexpresse
463	constitutive activation and constitutive phosphorylation of s-738 and s-742.
463	decreased phosphorylation level when coexpressed with either src or abl in hela cells. decreased kinase activity.
502	loss of activation.
502	decreased phosphorylation level when coexpressed with src in hela cells. unchanged phosphorylation level when coexpresse
612	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis
R-HSA-1430728	Metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 939 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, MODULE_97, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_METANEPHROS_DEVELOPMENT

GO Biological Process (53): angiogenesis (GO:0001525), positive regulation of endothelial cell proliferation (GO:0001938), apoptotic process (GO:0006915), inflammatory response (GO:0006954), Golgi organization (GO:0007030), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), integrin-mediated signaling pathway (GO:0007229), nervous system development (GO:0007399), positive regulation of autophagy (GO:0010508), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), regulation of keratinocyte proliferation (GO:0010837), positive regulation of neuron projection development (GO:0010976), regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril (GO:0014723), sphingolipid biosynthetic process (GO:0030148), cell differentiation (GO:0030154), cellular response to amino acid starvation (GO:0034198), cellular response to oxidative stress (GO:0034599), intracellular signal transduction (GO:0035556), cellular response to vascular endothelial growth factor stimulus (GO:0035924), positive regulation of protein import into nucleus (GO:0042307), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of blood vessel endothelial cell migration (GO:0043536), innate immune response (GO:0045087), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of angiogenesis (GO:0045766), positive regulation of cell size (GO:0045793), negative regulation of endocytosis (GO:0045806), positive regulation of transcription by RNA polymerase II (GO:0045944), protein autophosphorylation (GO:0046777), positive regulation of protein export from nucleus (GO:0046827), vascular endothelial growth factor receptor signaling pathway (GO:0048010), Golgi vesicle transport (GO:0048193), defense response to Gram-negative bacterium (GO:0050829), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), regulation of release of sequestered calcium ion into cytosol (GO:0051279), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of sarcomere organization (GO:0060298), transepithelial transport (GO:0070633)

GO Molecular Function (15): protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), protein kinase C binding (GO:0005080), ATP binding (GO:0005524), zinc ion binding (GO:0008270), kinase activity (GO:0016301), heat shock protein binding (GO:0031072), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), phosphatidylinositol 3-kinase activator activity (GO:0141038), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (12): autophagosome membrane (GO:0000421), nucleus (GO:0005634), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), cell cortex (GO:0005938), Z disc (GO:0030018), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
intracellular anatomical structure	2
protein kinase activity	2
protein binding	2
intracellular membrane-bounded organelle	2
cell periphery	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
organelle organization	1
endomembrane system organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
cell surface receptor signaling pathway	1
system development	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
keratinocyte proliferation	1
regulation of epithelial cell proliferation	1
regulation of neuron projection development	1
neuron projection development	1

Protein interactions and networks

STRING

1838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKD1	PKD1	P98161	893
PRKD1	HCLS1	P14317	854
PRKD1	CTTN	Q14247	853
PRKD1	PXN	P49023	843
PRKD1	ARF1	P10947	836
PRKD1	PKD2	Q13563	827
PRKD1	AKAP13	Q12802	806
PRKD1	PKD1L3	Q7Z443	785
PRKD1	ANKS6	Q68DC2	763
PRKD1	PKHD1	P08F94	733
PRKD1	PKD1L1	Q8TDX9	730
PRKD1	SSH1	Q8WYL5	724
PRKD1	TLN2	Q9Y4G6	717
PRKD1	TLN1	Q9Y490	711
PRKD1	KIAA0319L	Q8IZA0	690

IntAct

72 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
PRKD2	PRKD3	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PRKD3	PRKD1	psi-mi:“MI:0914”(association)	0.640
PRKD1	PRKD3	psi-mi:“MI:0914”(association)	0.640
C1QBP	PRKD1	psi-mi:“MI:0915”(physical association)	0.640
PRKD1	C1QBP	psi-mi:“MI:0915”(physical association)	0.640
C1QBP	PRKD1	psi-mi:“MI:0403”(colocalization)	0.640
PRKD1	C1QBP	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
MT2A	PRKD1	psi-mi:“MI:0915”(physical association)	0.590
PRKD1	MT2A	psi-mi:“MI:0915”(physical association)	0.590
PRKD1	MT2A	psi-mi:“MI:0403”(colocalization)	0.590
MAPK13	PRKD1	psi-mi:“MI:0915”(physical association)	0.590
PRKD1	MAPK13	psi-mi:“MI:0915”(physical association)	0.590
MAPK13	PRKD1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
PRKD1	CDH1	psi-mi:“MI:0403”(colocalization)	0.570
PRKD1	CDH1	psi-mi:“MI:0915”(physical association)	0.570
CDH1	PRKD1	psi-mi:“MI:0915”(physical association)	0.570

BioGRID (221): BAD (Affinity Capture-Western), PRKD1 (Affinity Capture-Western), PRKD1 (Reconstituted Complex), PRKD1 (Affinity Capture-MS), PRKD1 (Affinity Capture-Western), TFAP2A (Biochemical Activity), PRKD1 (Affinity Capture-Western), NOS1 (Two-hybrid), NOS1 (Reconstituted Complex), NOS1 (Biochemical Activity), PRKD1 (Affinity Capture-Western), USP28 (Affinity Capture-Western), USP28 (Biochemical Activity), PRKD1 (Affinity Capture-MS), PRKD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A2AWA9, A6QQZ7, A8KBF6, O55047, O88506, O95747, P20936, P23727, P26450, P27986, P31016, P78352, Q08CW1, Q08E27, Q12959, Q15139, Q15700, Q1ECX4, Q28C55, Q5PYH5, Q5PYH6, Q5PYH7, Q5R372, Q5R495, Q5R685, Q5R6Y5, Q5RAN1, Q5RCW6, Q5SRX1, Q5T2T1, Q5U2Y3, Q5ZIL4, Q5ZMW5, Q62101, Q62108, Q62696, Q63622, Q68FK8

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8WXF6, E9PT87, F1M0Z1, G4SLH0, O02827, O08875, O43293, O44997, O54784, O60229, O62305, O70150, O75962, O88764, O94768, O94806, P07313, P08414, P10911, P13234, P18652, P18653, P18654, P20689, P22216, P25323, P29294, P51812, P53355, P97924, Q00168, Q0KHT7, Q0KL02, Q14012, Q15139, Q15418

SIGNOR signaling

97 interactions.

A	Effect	B	Mechanism
PRKD1	down-regulates	RIN1	phosphorylation
PRKD1	unknown	RIN1	phosphorylation
PRKD1	“up-regulates activity”	PPP1R14A	phosphorylation
PRKCD	up-regulates	PRKD1	phosphorylation
PRKD1	down-regulates	HDAC7	phosphorylation
PRKD1	up-regulates	CDH1	phosphorylation
PRKD1	down-regulates	PIP4K2A	phosphorylation
PRKD1	up-regulates	PI4KB	phosphorylation
PRKD1	up-regulates	TLR5	phosphorylation
PRKD1	down-regulates	CERT1	phosphorylation
SRC	up-regulates	PRKD1	phosphorylation
PRKD1	down-regulates	BAD	phosphorylation
PRKD1	down-regulates	CTTN	phosphorylation
PRKD1	“down-regulates activity”	SNAI1	phosphorylation
PRKD1	down-regulates	DLC1	phosphorylation
PRKD1	down-regulates	OSBP	phosphorylation
PRKD1	down-regulates	SSH1	phosphorylation
PRKD1	up-regulates	CACNA1C	phosphorylation
PRKD1	up-regulates	PTRH2	phosphorylation
PRKD1	up-regulates	PRKD1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
intracellular signal transduction	8	7.1×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — CHOL, COADREAD, PRAD.

Clinical variants and AI predictions

ClinVar

7269 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1553
Likely pathogenic	499
Uncertain significance	3488
Likely benign	817
Benign	146

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013090	NM_001009944.3(PKD1):c.11263C>T (p.Gln3755Ter)	Pathogenic
1030954	NM_001009944.3(PKD1):c.5637C>A (p.Tyr1879Ter)	Pathogenic
1034359	NM_001009944.3(PKD1):c.8043_8046del (p.Ser2682fs)	Pathogenic
1048640	NM_001009944.3(PKD1):c.8333dup (p.Glu2779fs)	Pathogenic
1048641	NM_001009944.3(PKD1):c.5290G>T (p.Glu1764Ter)	Pathogenic
1048642	NM_001009944.3(PKD1):c.3931dup (p.Ala1311fs)	Pathogenic
1048645	NM_001009944.3(PKD1):c.5856del (p.Asn1954fs)	Pathogenic
1048760	NM_001009944.3(PKD1):c.499del (p.Gly168fs)	Pathogenic
1050228	NM_001009944.3(PKD1):c.8791+40_10050+3del	Pathogenic
1064647	NM_001009944.3(PKD1):c.11723T>C (p.Leu3908Pro)	Pathogenic
1077162	NM_001009944.3(PKD1):c.10527_10528del (p.Glu3509fs)	Pathogenic
1172882	NM_001009944.3(PKD1):c.1606+1G>A	Pathogenic
1177416	NM_001009944.3(PKD1):c.10219del (p.Ser3407fs)	Pathogenic
1177417	NM_001009944.3(PKD1):c.6282G>A (p.Trp2094Ter)	Pathogenic
1177427	NM_001009944.3(PKD1):c.10358dup (p.Ser3454fs)	Pathogenic
1179034	NM_001009944.3(PKD1):c.4743dup (p.Trp1582fs)	Pathogenic
1179054	NM_001009944.3(PKD1):c.160_166del (p.Arg54fs)	Pathogenic
1179066	NM_001009944.3(PKD1):c.10516del (p.Glu3506fs)	Pathogenic
1179071	NM_001009944.3(PKD1):c.9691G>T (p.Glu3231Ter)	Pathogenic
1179072	NM_001009944.3(PKD1):c.9683dup (p.Leu3229fs)	Pathogenic
1179075	NM_001009944.3(PKD1):c.659del (p.Gly220fs)	Pathogenic
1179077	NM_001009944.3(PKD1):c.6424C>T (p.Gln2142Ter)	Pathogenic
1179078	NM_001009944.3(PKD1):c.628_631dup (p.Ser211fs)	Pathogenic
1179089	NM_001009944.3(PKD1):c.272C>A (p.Ser91Ter)	Pathogenic
1179093	NM_001009944.3(PKD1):c.2054_2055del (p.Glu685fs)	Pathogenic
1179105	NM_001009944.3(PKD1):c.1326del (p.Ala443fs)	Pathogenic
1179107	NM_001009944.3(PKD1):c.10168C>T (p.Gln3390Ter)	Pathogenic
1179124	NM_001009944.3(PKD1):c.601dup (p.His201fs)	Pathogenic
1179125	NM_001009944.3(PKD1):c.5968_5969del (p.Arg1990fs)	Pathogenic
1179154	NM_001009944.3(PKD1):c.12383_12387del (p.Glu4128fs)	Pathogenic

SpliceAI

5228 predictions. Top by Δscore:

Variant	Effect	Δscore
14:29577452:TAGTC:T	acceptor_gain	1.0000
14:29577454:GTC:G	acceptor_gain	1.0000
14:29577455:TC:T	acceptor_gain	1.0000
14:29577456:CC:C	acceptor_gain	1.0000
14:29577456:CCTGA:C	acceptor_loss	1.0000
14:29577457:C:CC	acceptor_gain	1.0000
14:29577457:CTG:C	acceptor_loss	1.0000
14:29577458:T:A	acceptor_loss	1.0000
14:29578270:TTTA:T	donor_loss	1.0000
14:29578271:TTA:T	donor_loss	1.0000
14:29578272:TA:T	donor_loss	1.0000
14:29578274:C:CA	donor_loss	1.0000
14:29578356:AATGG:A	acceptor_gain	1.0000
14:29578357:ATGG:A	acceptor_gain	1.0000
14:29578358:TGG:T	acceptor_gain	1.0000
14:29578359:GG:G	acceptor_gain	1.0000
14:29578359:GGCT:G	acceptor_loss	1.0000
14:29578360:GCT:G	acceptor_loss	1.0000
14:29578361:C:A	acceptor_loss	1.0000
14:29578361:C:CC	acceptor_gain	1.0000
14:29578362:T:A	acceptor_loss	1.0000
14:29578376:A:T	acceptor_gain	1.0000
14:29599122:GTATC:G	acceptor_loss	1.0000
14:29599123:TAT:T	acceptor_gain	1.0000
14:29599123:TATCT:T	acceptor_loss	1.0000
14:29599124:ATC:A	acceptor_loss	1.0000
14:29599125:TCTGT:T	acceptor_loss	1.0000
14:29599126:C:A	acceptor_loss	1.0000
14:29599126:C:CC	acceptor_gain	1.0000
14:29599127:T:C	acceptor_loss	1.0000

AlphaMissense

6048 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:29578316:G:T	R827S	1.000
14:29578336:A:G	L820P	1.000
14:29597512:A:G	W805R	1.000
14:29597512:A:T	W805R	1.000
14:29597531:G:C	F798L	1.000
14:29597531:G:T	F798L	1.000
14:29597533:A:G	F798L	1.000
14:29597576:A:C	F783L	1.000
14:29597576:A:T	F783L	1.000
14:29597578:A:G	F783L	1.000
14:29597580:G:T	P782Q	1.000
14:29597582:G:C	F781L	1.000
14:29597582:G:T	F781L	1.000
14:29597584:A:G	F781L	1.000
14:29597589:C:T	G779D	1.000
14:29597591:G:C	S778R	1.000
14:29597591:G:T	S778R	1.000
14:29597593:T:G	S778R	1.000
14:29597595:A:G	L777P	1.000
14:29597597:G:C	S776R	1.000
14:29597597:G:T	S776R	1.000
14:29597599:T:G	S776R	1.000
14:29597616:C:T	G770E	1.000
14:29597617:C:A	G770W	1.000
14:29597617:C:G	G770R	1.000
14:29597617:C:T	G770R	1.000
14:29597624:C:A	W767C	1.000
14:29597624:C:G	W767C	1.000
14:29597626:A:G	W767R	1.000
14:29597626:A:T	W767R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003167 (14:29691474 A>G), RS1000010028 (14:29695222 G>A,T), RS1000010613 (14:29856093 G>T), RS1000013018 (14:29768720 A>C), RS1000026754 (14:29609719 T>TA,TC), RS1000031183 (14:29896367 C>T), RS1000040118 (14:29644151 A>G), RS1000052836 (14:29654971 A>G), RS1000060173 (14:29685736 G>C), RS1000063024 (14:29781357 T>C), RS1000075480 (14:29776625 C>A), RS1000077492 (14:29817358 C>A), RS1000088899 (14:29690335 T>C), RS1000119867 (14:29735562 C>T), RS1000119974 (14:29690018 C>A)

Disease associations

OMIM: gene MIM:605435 | disease phenotypes: MIM:173900, MIM:617364, MIM:613095, MIM:613254, MIM:191100, MIM:606690, MIM:607341, MIM:616371, MIM:119800, MIM:607086, MIM:610805, MIM:620442, MIM:300804, MIM:600666, MIM:174050, MIM:167000, MIM:600057, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive polycystic kidney disease	Definitive	Autosomal recessive
polycystic kidney disease 1	Definitive	Autosomal dominant
congenital heart defects and ectodermal dysplasia	Strong	Autosomal dominant
Caroli disease	Strong	Autosomal dominant
autosomal dominant polycystic kidney disease	Strong	Autosomal dominant
congenital heart defects, multiple types	Moderate	Autosomal recessive
congenital heart disease	Moderate	Autosomal recessive
complex neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (4)

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

Disease	Classification	Inheritance
autosomal dominant polycystic kidney disease	Definitive	AD
congenital heart disease	Limited	AD
congenital heart disease	Limited	AR
autosomal recessive polycystic kidney disease	Definitive	AR

Mondo (44): polycystic kidney disease 1 (MONDO:0008263), congenital heart defects and ectodermal dysplasia (MONDO:0044303), autosomal dominant polycystic kidney disease (MONDO:0004691), bile duct cancer (MONDO:0003059), hereditary ataxia (MONDO:0100309), kidney failure (MONDO:0001106), polycystic kidney disease 2 (MONDO:0013131), tuberous sclerosis 2 (MONDO:0013199), prostate cancer (MONDO:0008315), polycystic kidney disease (MONDO:0020642), tuberous sclerosis (MONDO:0001734), lymphangioleiomyomatosis (MONDO:0011705), isolated focal cortical dysplasia type II (MONDO:0011818), pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (MONDO:0014612), 46 XY differences of sex development (MONDO:0020040)

Orphanet (22): Autosomal dominant polycystic kidney disease (Orphanet:730), Hereditary ataxia (Orphanet:183518), Tuberous sclerosis complex (Orphanet:805), Familial prostate cancer (Orphanet:1331), Isolated focal cortical dysplasia type II (Orphanet:268994), Lymphangioleiomyomatosis (Orphanet:538), Idiopathic pulmonary fibrosis (Orphanet:2032), 46,XY difference of sex development (Orphanet:98085), Familial clubfoot with or without associated lower limb anomalies (Orphanet:199315), Familial aortic dissection (Orphanet:229), Renal or urinary tract malformation (Orphanet:93545), Multicystic dysplastic kidney (Orphanet:1851), Inherited cancer-predisposing syndrome (Orphanet:140162), Orofaciodigital syndrome type 6 (Orphanet:2754), Autosomal recessive polycystic kidney disease (Orphanet:731)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000639	Nystagmus
HP:0000687	Widely spaced teeth
HP:0000691	Microdontia
HP:0000750	Delayed speech and language development
HP:0000958	Dry skin
HP:0000963	Thin skin
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001328	Specific learning disability
HP:0001808	Fragile nails
HP:0001869	Deep plantar creases
HP:0002007	Frontal bossing
HP:0002209	Sparse scalp hair
HP:0002650	Scoliosis
HP:0003577	Congenital onset
HP:0005280	Depressed nasal bridge
HP:0005709	2-3 toe cutaneous syndactyly
HP:0006323	Premature loss of primary teeth
HP:0006695	Atrioventricular canal defect
HP:0007018	Attention deficit hyperactivity disorder
HP:0009890	High anterior hairline
HP:0010747	Medial flaring of the eyebrow
HP:0011304	Broad thumb
HP:0011968	Feeding difficulties
HP:0000822	Hypertension

GWAS associations

73 associations (top):

Study	Trait	p-value
GCST000830_33	Body mass index	6.000000e-11
GCST001762_252	Obesity-related traits	9.000000e-06
GCST002021_5	Body mass index	2.000000e-06
GCST002539_20	Schizophrenia	1.000000e-08
GCST002783_11	Body mass index	6.000000e-07
GCST002783_22	Body mass index	3.000000e-08
GCST002783_369	Body mass index	9.000000e-11
GCST002783_456	Body mass index	3.000000e-07
GCST002783_491	Body mass index	4.000000e-09
GCST002783_502	Body mass index	2.000000e-10
GCST003074_17	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	7.000000e-07
GCST003177_1	Childhood body mass index	7.000000e-07
GCST004065_11	Waist circumference	1.000000e-06
GCST004065_22	Waist circumference	3.000000e-08
GCST004162_33	Carotid plaque burden	4.000000e-06
GCST004495_74	BMI (adjusted for smoking behaviour)	1.000000e-06
GCST004497_30	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004557_105	Body mass index	2.000000e-08
GCST004557_206	Body mass index	3.000000e-08
GCST004557_236	Body mass index	2.000000e-08
GCST004557_24	Body mass index	1.000000e-08
GCST004558_102	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004558_156	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-07
GCST004558_175	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004558_21	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004559_100	Body mass index in physically active individuals	9.000000e-06
GCST004559_133	Body mass index in physically active individuals	5.000000e-06
GCST004559_53	Body mass index in physically active individuals	4.000000e-06
GCST005231_59	Major depressive disorder	7.000000e-06
GCST005316_526	Intelligence (MTAG)	7.000000e-09

EFO canonical traits (25, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0003939	energy intake
EFO:0007707	cerebral amyloid deposition measurement
EFO:0006501	carotid plaque build
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004337	intelligence
EFO:0006335	systolic blood pressure
EFO:0007660	neuroticism measurement
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0004338	body weight
EFO:0004784	self reported educational attainment
EFO:0009282	sodium measurement
EFO:0004874	memory performance
EFO:0008354	cognitive function measurement
EFO:0009695	household income
EFO:0009819	comparative body size at age 10, self-reported
EFO:0011015	educational attainment
EFO:0007828	daytime rest measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count
EFO:0004833	neutrophil count
EFO:0006941	grip strength measurement

MeSH disease descriptors (29)

Descriptor	Name	Tree numbers
D001660	Biliary Tract Diseases	C06.130
D016767	Caroli Disease	C06.130.120.127.500; C06.198.184.500; C16.131.077.245.250; C16.131.314.184.500; C16.320.184.250
D003025	Clubfoot	C05.330.488.655.063; C05.330.495.681.063; C05.660.585.512.380.813.063; C16.131.621.585.512.500.681.063
D003240	Connective Tissue Diseases	C17.300
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D006391	Hemangioma	C04.557.645.375
D006973	Hypertension	C14.907.489
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D052177	Kidney Diseases, Cystic	C12.050.351.968.419.403; C12.200.777.419.403; C12.950.419.403
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D018192	Lymphangioleiomyomatosis	C04.557.375.460.465; C04.557.450.692.500; C15.604.515.562.465; C20.683.515.710.465
D021782	Multicystic Dysplastic Kidney	C12.050.351.875.558; C12.050.351.968.419.403.750; C12.200.706.629; C12.200.777.419.403.750; C12.800.629; C12.950.419.403.750; C16.131.939.629
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
D051437	Renal Insufficiency	C12.050.351.968.419.780; C12.200.777.419.780; C12.950.419.780
D014402	Tuberous Sclerosis	C04.445.810; C04.651.800; C04.700.700; C10.500.507.400.750; C10.562.850; C10.574.500.865; C16.131.666.507.400.750; C16.320.400.880; C16.320.700.700
C562834	Aortic Aneurysm, Familial Thoracic 1 (supp.)
C566906	Cakut (supp.)
C537067	Focal cortical dysplasia of Taylor (supp.)
C531684	Hereditary spinal ataxia (supp.)
C567582	Joubert Syndrome 10 (supp.)
C536326	Polycystic kidney disease, type 1 (supp.)
C566021	Tuberous Sclerosis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL3863 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

26 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 510,148 (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
CHEMBL1863513	INGENOL MEBUTATE	4	1,475
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL180022	NERATINIB	4	9,404
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2	10,540
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL574737	UCN-01	2	2,217
CHEMBL1721885	SU-014813	2	363
CHEMBL495727	AT-9283	2	1,376
CHEMBL513909	BI-2536	2	895
CHEMBL1908397	KW-2449	1
CHEMBL296468	BMS-387032	1
CHEMBL3128043	PF-03758309	1
CHEMBL4169078	SRA-737	1
CHEMBL494089	GSK-690693	1
CHEMBL574738	AST-487	1

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs57803087	PRKD1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase D (PKD) family

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
compound 13c [PMID: 20684591]	Inhibition	9.22	pIC50
CRT 0066101	Inhibition	9.0	pIC50
BPKDi	Inhibition	9.0	pIC50
Gö 6976	Inhibition	7.7	pIC50
kb-NB142-70	Inhibition	7.55	pIC50
NIK SMI1	Inhibition	7.12	pKi

Binding affinities (BindingDB)

29 measured of 79 human assays (79 total across all organisms); most potent 29 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4442196	IC50	0.09 nM
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL4435580	IC50	0.22 nM
CHEMBL4587471	IC50	0.36 nM
CHEMBL4575056	EC50	0.6 nM
Staurosporine	KD	1.7 nM
kb-NB142-70	IC50	28.3 nM
PD-146626	IC50	82.5 nM
kb-NB165-92	IC50	111 nM
kb-NB165-31	IC50	114 nM
kb-NB184-02	IC50	193 nM
(2-amino-6-nitro-1,3-benzothiazol-7-yl)amine	IC50	410 nM
SCH772984	IC50	580 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
BMS-387072	KD	1800 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
3-ethyl-6-methoxy-1H-benzo[de]cinnoline	IC50	3280 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM
3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinamide;hydrochloride	IC50	6630 nM
6-(2-methyl-2,3-dihydro-1H-indol-1-yl)-5-nitro-4-pyrimidinamine	IC50	8220 nM
4-amino-7-(3,4-dihydroxy-5-methylol-tetrahydrofuran-2-yl)pyrrolo[2,3-d]pyrimidine-5-carboxamide;hydrate	IC50	12100 nM
CHEMBL411351	IC50	15000 nM
CHEMBL3215313	IC50	17000 nM
CHEMBL81478	IC50	30000 nM

ChEMBL bioactivities

496 potent at pChembl≥5 of 582 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	STAUROSPORINE
10.05	IC50	0.09	nM	CHEMBL4442196
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	IC50	0.15	nM	CHEMBL4528495
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.72	EC50	0.19	nM	CHEMBL3741746
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.40	IC50	0.4	nM	CHEMBL1215711
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	CHEMBL1214998
9.22	IC50	0.6	nM	STAUROSPORINE
9.05	Ki	0.9	nM	CHEMBL4113471
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL5440043
9.00	IC50	1	nM	CHEMBL5419827
9.00	IC50	1	nM	CHEMBL5428541
9.00	IC50	1	nM	CHEMBL1215710
9.00	IC50	1	nM	CHEMBL1215712
9.00	IC50	1	nM	CHEMBL1214711
9.00	IC50	1	nM	CHEMBL1214712
9.00	IC50	1	nM	CHEMBL1214860
9.00	IC50	1	nM	CHEMBL1215363
9.00	IC50	1	nM	CHEMBL1214999
9.00	IC50	1	nM	CHEMBL1215000
9.00	IC50	1	nM	CHEMBL1215001
9.00	IC50	1	nM	CHEMBL1215002
9.00	IC50	1	nM	CHEMBL1215074
9.00	IC50	1	nM	CHEMBL1215075
8.87	IC50	1.35	nM	STAUROSPORINE
8.82	IC50	1.5	nM	STAUROSPORINE
8.77	IC50	1.7	nM	CHEMBL291126
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL1215641
8.70	IC50	2	nM	CHEMBL1215643
8.70	IC50	2	nM	CHEMBL1214788
8.70	IC50	2	nM	CHEMBL1214858
8.70	IC50	2	nM	CHEMBL1214859
8.70	IC50	2	nM	CHEMBL1215220
8.66	IC50	2.2	nM	CHEMBL83790
8.57	IC50	2.7	nM	STAUROSPORINE
8.52	IC50	3	nM	STAUROSPORINE
8.52	IC50	3	nM	CHEMBL1215640
8.52	IC50	3	nM	CHEMBL1214710
8.52	IC50	3	nM	CHEMBL1214789
8.52	IC50	3	nM	CHEMBL1214857

PubChem BioAssay actives

394 with measured affinity, of 2095 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
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-22-acetyloxy-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] naphthalene-2-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,25R)-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-22-oxo-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	165147: Inhibition Protein kinase C (PKC)	ic50	0.0001	uM
3-cyclopropyl-10-[(3S)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-ynyl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0002	uM
3-N-methyl-10-[3-methyl-3-(5-methyl-1,3-oxazol-2-yl)but-1-ynyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2,3-dicarboxamide	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-nitrobenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-propan-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
3-cyclopropyl-10-[3-methyl-3-(5-methyl-1,3-oxazol-2-yl)but-1-ynyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-methoxybenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
3-cyclopropyl-9-fluoro-10-[(3R)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-ynyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0002	uM
10-[(3R)-3-hydroxy-3-(5-methyl-1,3-oxazol-2-yl)but-1-ynyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] pyridine-4-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0004	uM
N-(oxan-4-yl)-4-(1-piperazin-1-yl-2,6-naphthyridin-3-yl)pyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0004	uM
N-cyclohexyl-4-(1-piperazin-1-yl-2,6-naphthyridin-3-yl)pyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0006	uM
10-[(3R)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-ynyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0009	uM
2-[4-[[(2S)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol	1964575: Inhibition of PKD1 (unknown origin)	ic50	0.0010	uM
2-piperazin-1-yl-6-(2-piperidin-1-yl-4-pyridinyl)pyridine-4-carboxamide	1964575: Inhibition of PKD1 (unknown origin)	ic50	0.0010	uM
4-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)-2-pyridinyl]-N-propan-2-ylpyridin-2-amine	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
N-(oxan-4-yl)-4-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)-2-pyridinyl]pyridin-2-amine	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
4-[1-[4-(2-methylpropyl)piperazin-1-yl]-2,6-naphthyridin-3-yl]-N-(oxan-4-yl)pyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
4-[1-[4-(aminomethyl)piperidin-1-yl]-2,6-naphthyridin-3-yl]-N-cyclohexylpyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
1-[3-[2-(cyclohexylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]-N-(2-pyrrolidin-1-ylethyl)piperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]-N-(2-pyrrolidin-1-ylethyl)piperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
1-[3-[2-(cyclohexylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]-N-piperidin-4-ylpiperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
4-[2-(cyclohexylamino)-4-pyridinyl]-6-piperazin-1-yl-2,3-dihydropyrrolo[3,4-c]pyridin-1-one	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
2-(2-anilino-4-pyridinyl)-6-piperazin-1-ylpyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
2-[2-(oxan-4-ylamino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
2-piperazin-1-yl-6-[2-(propan-2-ylamino)-4-pyridinyl]pyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
2-[2-[(1-methylpyrazol-3-yl)amino]-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
2-[2-(2-chloroanilino)-4-pyridinyl]-6-piperazin-1-ylpyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
N-cyclohexyl-4-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)-2-pyridinyl]pyridin-2-amine	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0010	uM
3-[6-amino-5-(6-ethoxynaphthalen-2-yl)-3-pyridinyl]-N-[2-(dimethylamino)ethyl]benzamide	1964575: Inhibition of PKD1 (unknown origin)	ic50	0.0010	uM
(15R,16R,18S)-16-(hydroxymethyl)-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-3,5-dione	155717: In vitro inhibition of protein kinase C (PKC)	ic50	0.0017	uM
N-cyclohexyl-4-[1-(4-methylpiperazin-1-yl)-2,6-naphthyridin-3-yl]pyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0020	uM
2-[2-(cyclohexylamino)-4-pyridinyl]-6-[[(3R)-pyrrolidin-3-yl]amino]pyridine-4-carboxamide	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0020	uM
N-cyclohexyl-4-[1-[4-(cyclopropylmethyl)piperazin-1-yl]-2,6-naphthyridin-3-yl]pyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0020	uM
1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]piperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0020	uM
N-(2-methylpropyl)-1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]piperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0020	uM
N-(2-hydroxyethyl)-1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]piperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0020	uM
N-cyclohexyl-4-[1-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2,6-naphthyridin-3-yl]pyridin-2-amine	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0030	uM
1-[3-[2-(cyclohexylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]-N-methylpiperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0030	uM
N-ethyl-1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]piperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0030	uM
1-[3-[2-(oxan-4-ylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]-N-propan-2-ylpiperidine-4-carboxamide	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0030	uM
(2R)-4-[3-(2-aminopyrimidin-4-yl)-2-ethoxybenzimidazol-5-yl]-2-(5-methyl-1,3-oxazol-2-yl)but-3-yn-2-ol	1511444: Inhibition of full length GST-tagged human PRKD1 expressed in Baculovirus expression system using ATP as substrate incubated for 1 to 2 hrs by transcreener ADP assay based fluorescence correlation spectroscopic analysis	ki	0.0036	uM
N-[(1R)-1-cyanoethyl]-3-[5-[4-[(propan-2-ylamino)methyl]phenyl]-1H-pyrazol-3-yl]benzamide	580268: Inhibition of human PKD1 by TR-FRET assay	ic50	0.0037	uM
N-cyclohexyl-4-[6-piperazin-1-yl-4-(1H-pyrazol-5-yl)-2-pyridinyl]pyridin-2-amine	500132: Inhibition of PKD1 by TR-FRET assay	ic50	0.0040	uM
[1-[3-[2-(cyclohexylamino)-4-pyridinyl]-2,6-naphthyridin-1-yl]piperidin-4-yl]-(4-hydroxypiperidin-1-yl)methanone	500088: Inhibition of PKD1 by TR-FRET assay	ic50	0.0040	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	increases expression, affects phosphorylation, affects reaction, decreases reaction, increases phosphorylation (+1 more)	6
Benzo(a)pyrene	decreases expression, increases methylation	3
bisphenol A	decreases methylation, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Resveratrol	decreases phosphorylation, decreases activity	2
Air Pollutants	decreases expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
tributyltin	increases phosphorylation	1
ingenol dibenzoate	increases activity	1
butyraldehyde	decreases expression	1
manganese chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
12-deoxyphorbolphenylacetate-20-acetate	affects localization	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butyltin	increases phosphorylation	1
bisindolylmaleimide I	affects phosphorylation, affects reaction	1
perfluorooctane sulfonic acid	increases phosphorylation	1
thymeleatoxin	affects localization	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide	affects phosphorylation, affects reaction	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression, increases reaction	1
CRT 0066101	decreases reaction, increases phosphorylation	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1

ChEMBL screening assays

660 unique, capped per target: 650 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000235	Binding	Activation of PKC in PMA-stimulated human LNCAP cells assessed as ERK phosphorylation at 1 nM to 10 uM by Western blot relative to PMA	Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths. — J Med Chem
CHEMBL688555	Functional	Retained protein kinase C activity in the presence of 1.25 uM compound	Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C. — J Med Chem

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Q6	Abcam K-562 PRKD1 KO	Cancer cell line	Female
CVCL_D2LS	Abcam Raji PRKD1 KO	Cancer cell line	Male
CVCL_D7YM	Ubigene A-549 PRKD1 KO	Cancer cell line	Male
CVCL_D9PR	Ubigene HEK293 PRKD1 KO	Transformed cell line	Female
CVCL_TG96	HAP1 PRKD1 (-) 1	Cancer cell line	Male
CVCL_TG97	HAP1 PRKD1 (-) 2	Cancer cell line	Male
CVCL_WQ42	Abcam Jurkat PRKD1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00414440	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT03273413	PHASE4	ACTIVE_NOT_RECRUITING	Statin Therapy in Patients With Early Stage ADPKD
NCT03949894	PHASE4	COMPLETED	Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01256047	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy
NCT01969110	PHASE4	UNKNOWN	Additional Effects of Perioperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT04782258	PHASE3	RECRUITING	A Study to See Iftolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years Old withAutosomal Recessive Polycystic Kidney Disease (ARPKD)
NCT04786574	PHASE3	WITHDRAWN	A Study to See if Tolvaptan Can Delay Dialysis in Infants and Children Who at Enrollment Are 28 Days to Less Than 12 Weeks Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00309283	PHASE3	COMPLETED	Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study
NCT00346918	PHASE3	COMPLETED	Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)