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….

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): congenital heart defects and ectodermal dysplasia (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 55 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 295 total — 2 pathogenic, 8 likely-pathogenic
• GTEx eGene: eQTL in 18 tissues, sQTL in 12 (q < 0.05)
• Phenotypes (HPO): 29
• ChEMBL bioactivity: 26 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.76 (unconstrained)
• 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

MANE Select: ENST00000331968

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 3, TSL 4: 1, TSL 5: 2

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.

Highest expression (Bgee): ventricular zone, seminal vesicle, thoracic aorta, ascending aorta, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKD1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	5.3e-41	+0.84	14:29656454:A:G
Cells EBV-transformed lymphocytes	eqtl	7.8e-34	+0.86	14:29835170:C:CAT
Artery Tibial	sqtl	4.5e-18	+0.52	14:29677386:C:T
Spleen	eqtl	1.4e-15	+0.43	14:29835170:C:CAT
Nerve Tibial	sqtl	3.8e-11	+0.50	14:29653718:G:T
Cells Cultured fibroblasts	eqtl	2.7e-10	+0.19	14:30203284:A:C
Esophagus Muscularis	sqtl	7.3e-10	+0.46	14:29648196:AT:A
Artery Aorta	sqtl	1.1e-04	+0.45	14:29648196:AT:A
Adipose Subcutaneous	sqtl	3.5e-04	+0.32	14:29597723:A:G
Stomach	sqtl	1.4e-03	+0.48	14:29648196:AT:A
Lung	sqtl	2.2e-03	+0.37	14:29648196:AT:A
Stomach	eqtl	3.0e-03	-0.33	14:29927416:G:GCCCGGA
Nerve Tibial	eqtl	3.3e-03	+0.17	14:29836655:A:G
Colon Sigmoid	sqtl	4.0e-03	+0.43	14:29648897:G:A
Pancreas	eqtl	4.7e-03	+0.27	14:29605117:G:A
Muscle Skeletal	eqtl	5.3e-03	+0.15	14:30159179:T:C
Brain Cerebellar Hemisphere	eqtl	7.8e-03	-0.49	14:29822598:C:T
Colon Transverse	eqtl	8.6e-03	+0.09	14:29940197:C:T
Breast Mammary Tissue	eqtl	9.9e-03	+0.28	14:30146141:G:A
Brain Putamen basal ganglia	eqtl	1.0e-02	-0.24	14:29855771:C:A

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

showing 100 of 286 tissues 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
right ovary	UBERON:0002118	83.15	gold quality
metanephric glomerulus	UBERON:0004736	83.11	gold quality
left adrenal gland cortex	UBERON:0035825	82.62	gold quality
left adrenal gland	UBERON:0001234	82.45	gold quality
right lung	UBERON:0002167	82.42	gold quality
cartilage tissue	UBERON:0002418	82.41	gold quality
sural nerve	UBERON:0015488	82.31	gold quality
adrenal gland	UBERON:0002369	82.11	gold quality
kidney	UBERON:0002113	81.89	gold quality
adrenal cortex	UBERON:0001235	81.85	gold quality
right adrenal gland cortex	UBERON:0035827	81.81	gold quality
right adrenal gland	UBERON:0001233	81.80	gold quality
germinal epithelium of ovary	UBERON:0001304	81.70	gold quality
adult mammalian kidney	UBERON:0000082	81.67	gold quality
tibia	UBERON:0000979	81.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.46	gold quality
cortex of kidney	UBERON:0001225	81.27	gold quality
visceral pleura	UBERON:0002401	81.13	gold quality
embryo	UBERON:0000922	80.99	gold quality
calcaneal tendon	UBERON:0003701	80.90	gold quality
endometrium	UBERON:0001295	80.85	gold quality
kidney epithelium	UBERON:0004819	80.75	gold quality
left uterine tube	UBERON:0001303	80.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.29	gold quality
trigeminal ganglion	UBERON:0001675	80.26	gold quality
lower esophagus	UBERON:0013473	80.25	gold quality
omental fat pad	UBERON:0010414	80.19	gold quality
peritoneum	UBERON:0002358	80.18	gold quality
gall bladder	UBERON:0002110	79.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.81	gold quality
upper lobe of left lung	UBERON:0008952	79.79	gold quality
upper lobe of lung	UBERON:0008948	79.70	gold quality
myometrium	UBERON:0001296	79.59	gold quality
mucosa of stomach	UBERON:0001199	79.39	gold quality
adipose tissue	UBERON:0001013	78.74	gold quality
urinary bladder	UBERON:0001255	78.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.60	gold quality
body of uterus	UBERON:0009853	78.58	gold quality
smooth muscle tissue	UBERON:0001135	78.47	gold quality
nephron tubule	UBERON:0001231	78.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	78.44	gold quality
uterus	UBERON:0000995	78.40	gold quality
lower lobe of lung	UBERON:0008949	78.25	gold quality
right atrium auricular region	UBERON:0006631	78.21	gold quality
connective tissue	UBERON:0002384	78.18	gold quality
lung	UBERON:0002048	78.06	gold quality
caudate nucleus	UBERON:0001873	78.03	gold quality
pericardium	UBERON:0002407	77.82	gold quality
corpus callosum	UBERON:0002336	77.79	gold quality
body of pancreas	UBERON:0001150	77.68	gold quality
corpus epididymis	UBERON:0004359	77.61	gold quality
cauda epididymis	UBERON:0004360	77.57	gold quality
left lobe of thyroid gland	UBERON:0001120	77.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.13	gold quality
putamen	UBERON:0001874	77.04	gold quality
pancreas	UBERON:0001264	77.03	gold quality
thyroid gland	UBERON:0002046	77.01	gold quality
spinal cord	UBERON:0002240	77.01	gold quality
right lobe of thyroid gland	UBERON:0001119	76.99	gold quality
adenohypophysis	UBERON:0002196	76.99	gold quality
female reproductive system	UBERON:0000474	76.92	gold quality
dorsal root ganglion	UBERON:0000044	76.90	gold quality
tendon	UBERON:0000043	76.88	gold quality
islet of Langerhans	UBERON:0000006	76.50	gold quality
cardiac atrium	UBERON:0002081	76.48	gold quality
endocervix	UBERON:0000458	75.84	gold quality
pituitary gland	UBERON:0000007	75.79	gold quality
right frontal lobe	UBERON:0002810	75.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.49	gold quality
amygdala	UBERON:0001876	75.42	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Basal ganglia	tissue	20.6	medium
Putamen	tissue	20.4
Hippocampus	tissue	17.7	medium
Nucleus accumbens	tissue	14.4
Hypothalamus	tissue	13.7
Hippocampal formation	tissue	13.3
Ventral forebrain	tissue	13.3
Spinal cord	tissue	12.9
Postcentral gyrus	tissue	12.9
Periaqueductal gray	tissue	12.2
Locus coeruleus	tissue	12.1
Septum	tissue	12.0
Substantia nigra	tissue	11.9
Midbrain	tissue	11.7
Medulla oblongata	tissue	11.6
Pons	tissue	11.2
Amygdala	tissue	11.1
Prefrontal cortex	tissue	11.0
Cerebral cortex	tissue	11.0	medium
Motor cortex	tissue	11.0
Thalamus	tissue	11.0
Insular cortex	tissue	10.9
Choroid plexus	tissue	10.7
Caudate putamen	tissue	10.3
Retrosplenial and cingulate cortex	tissue	9.9
Retrosplenial cortex	tissue	9.9
Entorhinal cortex	tissue	9.7
Superior colliculi	tissue	9.5
Temporal cortex	tissue	9.5
Occipital cortex	tissue	8.8
Somatosensory cortex	tissue	8.6
Corpus callosum	tissue	8.4
Cerebellum	tissue	7.4	medium
Olfactory bulb	tissue	7.3
Frontal cortex	tissue	6.4
Testis	tissue	5.4	medium
Prostate	tissue	4.3	low
Parathyroid gland	tissue	3.8	medium
Seminal vesicle	tissue	3.6	low
Ovary	tissue	2.9	medium
Kidney	tissue	2.9	medium
Smooth muscle	tissue	2.4	low
Gallbladder	tissue	1.9	medium
Adrenal gland	tissue	1.9	medium
Retina	tissue	1.8
Thyroid gland	tissue	1.8	medium
Adipose tissue	tissue	1.7	not detected
Urinary bladder	tissue	1.6	high
Endometrium 1	tissue	1.6	medium
Tongue	tissue	1.6
Lung	tissue	1.5	medium
Pituitary gland	tissue	1.2
Vagina	tissue	1.2	medium
Fallopian tube	tissue	1.2	low
Cervix	tissue	1.0	low
Heart muscle	tissue	1.0	medium
Appendix	tissue	1.0	medium
Esophagus	tissue	0.9	medium
Placenta	tissue	0.9	medium
Pancreas	tissue	0.8	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal funiculus (white matter) (22.9), Cervical spinal cord, dorsal horn (20.6), Area postrema (20.4), Periaquaductal grey, dorsal (20.3), Medial olivary nucleus (20.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

Targeting PRKD1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 77 miRNAs:

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

gnomAD constraint: pLI 3e-09, LOEUF 0.762, missense Z 0.973 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000331968 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:29,577,241–29,663,719	739 / 861.9	0.86	no
14:29,663,720–29,927,403	275 / 248.6	1.11	no
14:29,927,404–29,927,512	34 / 54.8	0.62	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity Not yet evaluated (unscored). 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

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkd1	ENSDARG00000075949
mus_musculus	Prkd1	ENSMUSG00000002688
rattus_norvegicus	Prkd1	ENSRNOG00000004165
drosophila_melanogaster	PKD	FBGN0038603
caenorhabditis_elegans		WBGENE00011254
caenorhabditis_elegans		WBGENE00018620
caenorhabditis_elegans		WBGENE00018621

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99879) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased leukocyte cell number	1
abnormal heart rate	1
increased circulating insulin level	1
increased heart weight	1
cardiac fibrosis	1
abnormal heart left ventricle morphology	1
increased mean corpuscular hemoglobin	1
increased cardiac muscle contractility	1
increased mean corpuscular hemoglobin concentration	1
perinatal lethality, incomplete penetrance	1
embryonic lethality, incomplete penetrance	1
embryonic lethality during organogenesis, incomplete penetrance	1
lethality throughout fetal growth and development, incomplete penetrance	1
increased myelin sheath thickness	1
increased susceptibility to induction of seizure by inducing agent	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A6N9I4	96.7%	Diamond
Xenopus laevis	Q32N25	95.6%	Diamond
Xenopus tropicalis	A4IJ06	95.2%	Diamond
Mesocricetus auratus	Q64398	94.2%	Diamond
Caenorhabditis briggsae	A8XWC4	84.3%	Diamond
Dictyostelium discoideum	Q55CY9	62.2%	Diamond
Schizosaccharomyces pombe 972h-	Q09746	53.7%	Diamond
Aspergillus nidulans FGSC A4	P0C1B1	49.2%	Diamond
Arabidopsis thaliana	Q94C95	45.1%	Diamond
Saccharomyces cerevisiae S288C	P39009	40.9%	Diamond
Equine herpesvirus type 1 (strain AB4P)	P28926	100.0%	Diamond
Equine herpesvirus 1 (strain V592)	P84390	100.0%	Diamond
Equine herpesvirus type 1 (strain Kentucky A)	P32516	99.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
G2E3-AS1	ncRNA	105370431
LINC02327	ncRNA	102724917
LINC02326	ncRNA	105370425
LINC03199	ncRNA	102724934

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, H0YHL5, H0YHS9, Q15139

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. Acts as a regulator of social behavior by mediating phosphorylation of OXTR, enhancing G(q)-dependent G protein-coupled receptor signaling.

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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, CAMK Ser/Thr protein kinases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the circulatory system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol

Antibody reliability (HPA): IH uncertain · IF supported

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)

Position	Role
706	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
589–597	ATP
612	ATP

Post-translational modifications (18)

Type	Positions
Phosphoserine	205, 208, 219, 223, 345, 397, 401, 448, 473, 548, 738, 742, 910
Phosphotyrosine	432, 463, 502, 749, 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 coexpressed with abl.
432	decreased phosphorylation level when coexpressed with src in hela cells. unchanged phosphorylation level when coexpressed with abl …
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 coexpressed with abl …
612	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

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

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 (50): 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), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of sarcomere organization (GO:0060298), transepithelial transport (GO:0070633), cellular response to hydroperoxide (GO:0071447), cellular response to norepinephrine stimulus (GO:0071874), positive regulation of peptide hormone secretion (GO:0090277), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), cellular response to angiotensin (GO:1904385), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), cellular response to endothelin (GO:1990859), positive regulation of endothelial cell chemotaxis (GO:2001028), regulation of integrin-mediated signaling pathway (GO:2001044), immune system process (GO:0002376), protein phosphorylation (GO:0006468), response to norepinephrine (GO:0071873)

GO Molecular Function (16): protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), diacylglycerol-dependent, calcium-independent serine/threonine kinase activity (GO:0004699), 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

3 top-level categories:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

showing 60 of 75 GO namespaces:

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
animal gross anatomical part developmental process	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
positive regulation of cell projection organization	1
regulation of skeletal muscle contraction by calcium ion signaling	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
cellular developmental process	1
cellular response to starvation	1
response to amino acid starvation	1
response to oxidative stress	1
cellular response to chemical stress	1
signal transduction	1
protein serine/threonine kinase activity	1
diacylglycerol-dependent serine/threonine kinase activity	1
protein kinase binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transition metal ion binding	1
transferase activity, transferring phosphorus-containing groups	1
phosphatidylinositol 3-kinase regulator activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 30 of 78 annotations. The rest are phylogenetic / computational / electronic (IEA).

30 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi organization	BP	mutant phenotype
cellular response to amino acid starvation	BP	mutant phenotype
cellular response to hydroperoxide	BP	mutant phenotype
cellular response to oxidative stress	BP	direct assay
cellular response to vascular endothelial growth factor stimulus	BP	mutant phenotype
intracellular signal transduction	BP	mutant phenotype
positive regulation of angiogenesis	BP	mutant phenotype
positive regulation of autophagy	BP	mutant phenotype
positive regulation of blood vessel endothelial cell migration	BP	mutant phenotype
positive regulation of canonical NF-kappaB signal transduction	BP	mutant phenotype
positive regulation of endothelial cell chemotaxis	BP	mutant phenotype
positive regulation of endothelial cell migration	BP	mutant phenotype
positive regulation of endothelial cell proliferation	BP	genetic interaction
positive regulation of neuron projection development	BP	mutant phenotype
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	mutant phenotype
protein autophosphorylation	BP	direct assay
transepithelial transport	BP	direct assay
vascular endothelial growth factor receptor signaling pathway	BP	mutant phenotype
Golgi apparatus	CC	direct assay
autophagosome membrane	CC	direct assay
cytosol	CC	direct assay
plasma membrane	CC	direct assay
trans-Golgi network	CC	direct assay
diacylglycerol-dependent serine/threonine kinase activity	MF	direct assay
identical protein binding	MF	physical interaction
kinase activity	MF	direct assay
phosphatidylinositol 3-kinase activator activity	MF	direct assay
protein serine kinase activity	MF	genetic interaction
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,586 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKD1	PKD1	P98161	854
PRKD1	PKD1L3	Q7Z443	786
PRKD1	PKD2	Q13563	771
PRKD1	PKD1L1	Q8TDX9	731
PRKD1	ANKS6	Q68DC2	727
PRKD1	KIAA0319L	Q8IZA0	715
PRKD1	SSH1	Q8WYL5	699
PRKD1	PLEK2	Q9NYT0	638
PRKD1	PKHD1	P08F94	630
PRKD1	PLEK	P08567	626
PRKD1	HDAC5	Q9UQL6	606
PRKD1	HSPB1	P04792	590
PRKD1	PI4KB	P78405	584
PRKD1	NPHP3	Q7Z494	579
PRKD1	RHOA	P06749	578

IntAct

Human interaction partners of PRKD1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
C1QBP	physical association	0.640	9
PRKD3	association	0.640	2
MT2A	physical association	0.590	7
MAPK13	physical association	0.590	5
CDH1	colocalization	0.570	7
HSP90AB1	physical association	0.520	2
ARFIP1	phosphorylation reaction	0.440	2
MARK2	phosphorylation reaction	0.440	1
PKM	phosphorylation reaction	0.440	1
PRKCE	phosphorylation reaction	0.440	1
MYO1C	association	0.350	1
NHERF2	physical association	0.000	1
YAP1	physical association	0.000	1

BioGRID (223 interactions; top human partners by supporting records): AKAP13 (Reconstituted Complex; 4 records), C1QBP (Affinity Capture-Western; 4 records), HDAC5 (Affinity Capture-Western; 4 records), NOS1 (Affinity Capture-Western; 4 records), YWHAQ (Affinity Capture-MS; 4 records), BTK (Affinity Capture-Western; 3 records), HSPB1 (Affinity Capture-MS; 3 records), PRKD2 (Affinity Capture-MS; 3 records), PRKD3 (Affinity Capture-MS; 3 records), USP28 (Affinity Capture-Western; 3 records), YWHAZ (Reconstituted Complex; 3 records), ADAP1 (Reconstituted Complex; 2 records), BAD (Affinity Capture-Western; 2 records), COPS7A (Affinity Capture-Western; 2 records), FUCA1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 36 of 97 signaling 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
MAPK13	down-regulates	PRKD1	phosphorylation
PRKD1	up-regulates	CTNNB1	phosphorylation
PRKD1	down-regulates	HDAC5	phosphorylation
PRKD1	up-regulates	ARFIP1	phosphorylation
ABL1	unknown	PRKD1	phosphorylation
SRC	“up-regulates activity”	PRKD1	phosphorylation
PRKD1	“down-regulates activity”	PLCG1	phosphorylation
ABL1	“up-regulates activity”	PRKD1	phosphorylation
PRKD1	“up-regulates activity”	PKD2	phosphorylation
PRKD1	“up-regulates activity”	ATP7B	phosphorylation
PRKD1	“up-regulates activity”	REM1	phosphorylation
PRKD1	“up-regulates activity”	PIK3R1	phosphorylation
PRKD1	“up-regulates activity”	MFF	phosphorylation
PRKD1	“down-regulates activity”	KCNH2	phosphorylation
PRKD1	“up-regulates quantity by stabilization”	KAT7	phosphorylation
PRKD1	“up-regulates activity”	RABEP1	phosphorylation

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for PRKD1: 295 ClinVar records (10 pathogenic / likely pathogenic); 55 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	8
Uncertain significance	201
Likely benign	51
Benign	13

Top pathogenic / likely-pathogenic (10)

Showing all 10 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
803014	NM_002742.3(PRKD1):c.1316G>A (p.Arg439Gln)	Likely pathogenic	criteria provided, single submitter	1
1691270	NM_002742.3(PRKD1):c.1905+2T>A	Likely pathogenic	criteria provided, single submitter	1
3064443	NM_002742.3(PRKD1):c.265-1G>T	Likely pathogenic	criteria provided, single submitter	1
3783367	NM_002742.3(PRKD1):c.1841T>C (p.Ile614Thr)	Likely pathogenic	criteria provided, single submitter	1
3893293	NM_002742.3(PRKD1):c.1906-1G>T	Likely pathogenic	criteria provided, single submitter	1
4278079	NM_002742.3(PRKD1):c.2026_2038del (p.Gly676fs)	Likely pathogenic	criteria provided, single submitter	1
4688159	NM_002742.3(PRKD1):c.1807C>T (p.Arg603Cys)	Likely pathogenic	criteria provided, single submitter	1
4819140	NM_002742.3(PRKD1):c.1783G>A (p.Gly595Arg)	Likely pathogenic	criteria provided, single submitter	1
375740	NM_002742.3(PRKD1):c.1774G>A (p.Gly592Arg)	Pathogenic	no assertion criteria provided	1
375741	NM_002742.3(PRKD1):c.896T>G (p.Leu299Trp)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRKD1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 2,971):

Position(s)	Effect	Δscore	Sites
14:29577457–29577458	acceptor_loss	1.0000	5
14:29578273–29578274	donor_loss	1.0000	6
14:29578361–29578362	acceptor_loss	1.0000	5
14:29578376	acceptor_gain	1.0000
14:29599126–29599127	acceptor_loss	1.0000	6
14:29599654–29599655	donor_loss	1.0000	5
14:29599818–29599819	acceptor_loss	1.0000	4
14:29624150–29624151	donor_loss	1.0000	6
14:29624259–29624260	acceptor_loss	1.0000	4
14:29624260–29624261	acceptor_gain	1.0000	2

AlphaMissense

3,013 missense substitutions predicted likely pathogenic (of 6,048 scored), across 601 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M659	9	0.988	0.999
M648	9	0.946	0.993
M666	9	0.936	0.997
M407	9	0.914	0.987
M166	9	0.908	0.998
M766	9	0.887	0.998
M669	9	0.866	0.981
D706	8	1.000	1.000
N711	8	1.000	1.000
D727	8	1.000	1.000
D765	8	0.999	1.000
H106	8	0.998	1.000
H185	8	0.998	0.999
D665	8	0.998	1.000
H147	8	0.997	0.999
H271	8	0.997	1.000
H309	8	0.997	0.999
F728	8	0.997	1.000
F739	8	0.997	1.000
H704	8	0.996	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.42e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000218
Thyroid Carcinoma (TCGA)	unfavorable	0.000348

Disease associations

OMIM: gene MIM:605435 | disease phenotypes: MIM:617364

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital heart defects and ectodermal dysplasia	Definitive	Autosomal dominant	4
congenital heart defects, multiple types	Moderate	Autosomal recessive
congenital heart disease	Moderate	Autosomal recessive	2
complex neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

2 validity classifications:

Disease	Classification	Inheritance
congenital heart disease	Limited	AD
congenital heart disease	Limited	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Ectodermal dysplasia	green
Fetal anomalies	green
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

Mondo (4): congenital heart defects and ectodermal dysplasia (MONDO:0044303), congenital heart defects, multiple types (MONDO:0000119), complex neurodevelopmental disorder (MONDO:0100038), congenital heart disease (MONDO:0005453)

HPO phenotypes

29 phenotypes (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

GWAS associations

showing 30 of 55 associations:

Study	Trait	p-value
GCST010989_161	Body size at age 10	1e-20
GCST010988_46	Adult body size	6e-18
GCST011494_8	Daytime nap	1e-14
GCST008647_41	Urinary sodium excretion	1e-11
GCST000830_33	Body mass index	6e-11
GCST002783_535	Body mass index	9e-11
GCST002783_61	Body mass index	2e-10
GCST006269_1114	General cognitive ability	2e-10
GCST006624_82	Systolic blood pressure	4e-10
GCST006803_54	Schizophrenia	4e-10
GCST008595_82	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	4e-10
GCST006269_9	General cognitive ability	8e-10
GCST002783_92	Body mass index	4e-9
GCST005316_460	Intelligence (MTAG)	4e-9
GCST005316_459	Intelligence (MTAG)	7e-9
GCST002539_30	Schizophrenia	1e-8
GCST004557_206	Body mass index	1e-8
GCST009524_186	Household income (MTAG)	1e-8
GCST010988_47	Adult body size	1e-8
GCST004557_186	Body mass index	2e-8
GCST004557_21	Body mass index	2e-8
GCST006940_1	Neurociticism	2e-8
GCST008152_18	Weight	2e-8
GCST002783_397	Body mass index	3e-8
GCST004065_67	Waist circumference	3e-8
GCST004557_60	Body mass index	3e-8
GCST007325_1	General risk tolerance (MTAG)	3e-8
GCST008575_13	IgM levels	5e-8
GCST007201_391	Schizophrenia	6e-8
GCST008162_96	Hip circumference	8e-8

EFO canonical traits (from GWAS)

19 canonical traits:

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: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

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 518,375 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

26 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL939	GEFITINIB	4	119,425
CHEMBL1863513	INGENOL MEBUTATE	4	1,527
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL180022	NERATINIB	4	9,891
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL535	SUNITINIB	4	80,232
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL38380	FASUDIL	3	12,137
CHEMBL603469	LESTAURTINIB	3
CHEMBL265502	SURAMIN	3	37,133
CHEMBL495727	AT-9283	2	1,442
CHEMBL513909	BI-2536	2	932
CHEMBL28509	EDELFOSINE	2	10,657
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,427
CHEMBL1721885	SU-014813	2	375
CHEMBL574737	UCN-01	2	2,319
CHEMBL3137336	UPROSERTIB	2	1,706
CHEMBL574738	AST-487	1
CHEMBL296468	BMS-387032	1
CHEMBL494089	GSK-690693	1
CHEMBL1908397	KW-2449	1
CHEMBL3128043	PF-03758309	1
CHEMBL4169078	SRA-737	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs57803087	linagliptin, saxagliptin, sitagliptin, vildagliptin	Efficacy	Allele G is associated with increased response to linagliptin, saxagliptin, sitagliptin or vildagliptin in people with Diabetes Mellitus, Type 2 as compared to allele A.	PMID:28160554

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)

373 measured of 560 human assays (583 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4442196	IC50	0.09 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4524153	KI	0.16 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL6144731	KD	0.18 nM
CHEMBL3741746	EC50	0.19 nM
CHEMBL4435580	IC50	0.22 nM
10-[(3S)-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	KI	0.29 nM	US-9034866: Tricyclic compounds and methods of use therefor
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	KI	0.29 nM	US-9034866: Tricyclic compounds and methods of use therefor
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	KI	0.3 nM	US-9034866: Tricyclic compounds and methods of use therefor
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	KI	0.31 nM	US-9034866: Tricyclic compounds and methods of use therefor
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
4-(1-Piperazin-1-yl[2,6]naphthyridin-3-yl)pyridin-2-yl](tetrahydropyran-4-yl)amine	IC50	0.4 nM
CHEMBL4587471	EC50	0.55 nM
CHEMBL4575056	EC50	0.6 nM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	IC50	1 nM	US-8530652: Pyrrolopyrazoles, potent kinase inhibitors
10-[(3R)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-ynyl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide	KI	1 nM	US-9034866: Tricyclic compounds and methods of use therefor
1-[3-(2-Cyclohexylaminopyridin-4-yl)[2,6]naphthyridin-1-yl]-piperidine-4-carboxylic Acid Piperidin-4-ylamide	IC50	1 nM
{4-[1-(4-Isobutylpiperazin-1-yl)[2,6]naphthyridin-3-yl]pyridin-2-yl}(tetrahydropyran-4-yl)amine	IC50	1 nM
N-(2-(pyrrolidin-1-yl)ethyl)-1-(3-(2-(tetrahydro-2H-pyran-4-ylamino)pyridin-4-yl)-2,6-naphthyridin-1-yl)piperidine-4-carboxamide	IC50	1 nM
1-[3-(2-Cyclohexylaminopyridin-4-yl)[2,6]naphthyridin-1-yl]piperidine-4-carboxylic Acid(2-Pyrrolidin-1-ylethyl)amide	IC50	1 nM
1-{3-[2-(Tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic Acid(2-Pyrrolidin-1-ylethyl)-amide	IC50	1 nM
2’-Phenylamino-6-piperazin-1-yl[2,4’]bipyridinyl-4-carboxylic Acid Methyl Amide	IC50	1 nM
Cyclohexyl-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)[2,4’]bipyridinyl-2’-yl]amine	IC50	1 nM
CHEMBL5440043	IC50	1 nM
CHEMBL5419827	IC50	1 nM
CHEMBL5428541	IC50	1 nM
Compound K-252a(epi)	IC50	1.2 nM
Staurosporine	KD	1.7 nM
Cyclohexyl-{4-[1-(4-methylpiperazin-1-yl)[2,6]naphthyridin-3-yl]pyridin-2-yl}amine	IC50	2 nM
Cyclohexyl-{4-[1-(4-cyclopropylmethylpiperazin-1-yl)[2,6]naphthyridin-3-yl]pyridin-2-yl}amine	IC50	2 nM
1-{3-[2-(Tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic Acid Amide	IC50	2 nM
1-{3-[2-(Tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic Acid Isobutylamide	IC50	2 nM
1-{3-[2-(Tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic Acid(2-Hydroxyethyl)amide	IC50	2 nM
Isopropyl-[6-piperazin-1-yl-4-(1H-pyrazol-4-yl)[2,4’]bipyridinyl-2’-yl]amine	IC50	2 nM
6-(piperazin-1-yl)-4-(4H-pyrazol-4-yl)-N-(tetrahydro-2H-pyran-4-yl)-2,4’-bipyridin-2’-amine	IC50	2 nM
CHEMBL83790	IC50	2.2 nM
2-({4-[3-(4-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}amino)propan-1-ol	IC50	3 nM
Cyclohexyl-{4-[1-((cis-3,5-dimethylpiperazin-1-yl)[2,6]naphthyridin-3-yl]pyridin-2-yl}amine	IC50	3 nM
1-[3-(2-Cyclohexylaminopyridin-4-yl)[2,6]naphthyridin-1-yl]piperidine-4-carboxylic Acid Methylamide	IC50	3 nM
1-{3-[2-(Tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylicAcidEthylamide	IC50	3 nM
1-{3-[2-(Tetrahydropyran-4-ylamino)pyridin-4-yl][2,6]naphthyridin-1-yl}piperidine-4-carboxylic Acid Isopropylamide	IC50	3 nM
corilagin	EC50	3.2 nM
CEP-701	KD	3.4 nM
2-Amino-1-(4-{3-[2-(tetrahydropyran-4-ylamino)pyridin-4-yl]-[2,6]naphthyridin-1-yl}piperazin-1-yl)ethanone	IC50	5 nM
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
Staurosporine, 8	IC50	6.5 nM
2’-(1-Methyl-1H-pyrazol-3-ylamino)-6-piperazin-1-yl[2,4’]bipyridinyl-4-carboxylic Acid Amide	IC50	7 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

398 with measured affinity, of 2109 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	affects localization, increases expression, affects phosphorylation, affects reaction, decreases reaction (+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)	affects cotreatment, decreases expression	1
12-deoxyphorbolphenylacetate-20-acetate	affects localization	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	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	affects cotreatment, decreases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 600 trials:

NCT	Phase	Status	Title
NCT00668824	Phase 4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	Phase 4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	Phase 4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	Phase 4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	Phase 4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	Phase 4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	Phase 4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	Phase 4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	Phase 4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	Phase 4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	Phase 4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	Phase 4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	Phase 4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRKD1 across ~30M SureChEMBL compounds — explore on Sugi Predict.