PRKCD

Summary

PRKCD (protein kinase C delta, HGNC:9399) is a protein-coding gene on chromosome 3p21.1, encoding Protein kinase C delta type (Q05655). Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic prote….

The protein encoded by this gene is a member of the protein kinase C family of serine- and threonine-specific protein kinases. The encoded protein is activated by diacylglycerol and is both a tumor suppressor and a positive regulator of cell cycle progression. Also, this protein can positively or negatively regulate apoptosis. Defects in this gene are a cause of autoimmune lymphoproliferative syndrome.

Source: NCBI Gene 5580 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 599 total — 13 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes — 49 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_006254

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9399
Approved symbol	PRKCD
Name	protein kinase C delta
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163932
Ensembl biotype	protein_coding
OMIM	176977
Entrez	5580

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 38 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000330452, ENST00000394729, ENST00000464818, ENST00000477794, ENST00000478843, ENST00000487897, ENST00000650739, ENST00000650940, ENST00000651505, ENST00000652449, ENST00000654719, ENST00000697588, ENST00000697589, ENST00000697590, ENST00000883491, ENST00000883492, ENST00000883493, ENST00000928336, ENST00000928337, ENST00000928338, ENST00000928339, ENST00000928340, ENST00000949457, ENST00000949458, ENST00000949459, ENST00000949460, ENST00000949461, ENST00000949462, ENST00000949463, ENST00000949464, ENST00000949465, ENST00000949466, ENST00000949467, ENST00000949468, ENST00000949469, ENST00000949470, ENST00000949471, ENST00000949472, ENST00000949473, ENST00000949474, ENST00000949475, ENST00000949476

RefSeq mRNA: 7 — MANE Select: NM_006254 NM_001316327, NM_001354676, NM_001354678, NM_001354679, NM_001354680, NM_006254, NM_212539

CCDS: CCDS2870

Canonical transcript exons

ENST00000330452 — 19 exons

Exon	Start	End
ENSE00001079749	53181444	53181606
ENSE00001079750	53179577	53179776
ENSE00001079751	53186604	53186695
ENSE00001079752	53183121	53183206
ENSE00001079754	53187340	53187402
ENSE00001079755	53185927	53186027
ENSE00001079756	53181701	53181732
ENSE00001079757	53186167	53186340
ENSE00001079760	53188720	53188858
ENSE00001079761	53185604	53185700
ENSE00001079762	53184874	53184974
ENSE00001079764	53189873	53190001
ENSE00001079766	53189058	53189246
ENSE00001079767	53183452	53183581
ENSE00001297556	53161209	53161428
ENSE00001321750	53192108	53192717
ENSE00001339281	53165104	53165215
ENSE00003784881	53181207	53181267
ENSE00003851003	53178404	53178537

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8011 / max 981.7375, expressed in 1799 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36913	21.7824	1793
36914	2.9025	971
36918	1.5323	211
36915	1.3837	286
36916	0.1785	46
36919	0.0217	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.31	gold quality
mononuclear cell	CL:0000842	98.00	gold quality
leukocyte	CL:0000738	97.96	gold quality
granulocyte	CL:0000094	97.73	gold quality
right adrenal gland cortex	UBERON:0035827	95.82	gold quality
right uterine tube	UBERON:0001302	95.74	gold quality
mucosa of transverse colon	UBERON:0004991	95.69	gold quality
right adrenal gland	UBERON:0001233	95.63	gold quality
left adrenal gland	UBERON:0001234	95.20	gold quality
left adrenal gland cortex	UBERON:0035825	95.03	gold quality
right lobe of thyroid gland	UBERON:0001119	94.90	gold quality
left lobe of thyroid gland	UBERON:0001120	94.53	gold quality
rectum	UBERON:0001052	93.83	gold quality
adrenal cortex	UBERON:0001235	93.68	gold quality
upper lobe of left lung	UBERON:0008952	93.66	gold quality
adrenal gland	UBERON:0002369	93.55	gold quality
blood	UBERON:0000178	93.36	gold quality
gall bladder	UBERON:0002110	93.28	gold quality
spleen	UBERON:0002106	93.22	gold quality
right lung	UBERON:0002167	93.10	gold quality
thyroid gland	UBERON:0002046	92.95	gold quality
upper lobe of lung	UBERON:0008948	92.77	gold quality
bone marrow cell	CL:0002092	92.65	gold quality
body of stomach	UBERON:0001161	92.59	gold quality
lower esophagus mucosa	UBERON:0035834	92.39	gold quality
endometrium epithelium	UBERON:0004811	92.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.14	gold quality
transverse colon	UBERON:0001157	91.98	gold quality
skin of abdomen	UBERON:0001416	91.60	gold quality
right coronary artery	UBERON:0001625	91.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	522.67
E-ANND-3	yes	17.79
E-MTAB-9067	yes	11.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATF2, AZU1, ESR1, JUN, NFKB, PDGFB, SP1

miRNA regulators (miRDB)

47 targeting PRKCD, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-510-3P	99.54	70.06	2965

Literature-anchored findings (GeneRIF, showing 40)

• PKC-delta selectively inhibits H2 histamine receptor-mediated activation of nonselective cation channels in differentiating granulocytic cells. (PMID:11466390)
• Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta. (PMID:11676480)
• role in regulation of eosinophil NADPH oxidase activity (PMID:11748588)
• that the PKC delta pathway plays an important role int the control of human keratinocyte migration (PMID:11822877)
• activation by type I interferons and mediation of Stat1 phosphorylation on serine 727 (PMID:11839738)
• Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta. (PMID:11864971)
• Switch chimeras, containing the C1B from epsilonPKC in the context of deltaPKC (delta(epsilonC1B)) and vice versa (epsilon(deltaC1B)), were generated and tested for their translocation in response to ceramide and arachidonic acid. (PMID:11877428)
• Phosphorylation of MUC1 by PKCdelta increases binding of MUC1 and beta-catenin in vitro and in vivo. (PMID:11877440)
• results indicate that PKCdelta plays a crucial role in activating anticancer drug-induced apoptosis signaling by amplifying the ceramide-mediated mitochondrial amplification loop. (PMID:11901191)
• PMA activated the promoter activity of the 12(S)-lipoxygenase gene in cells PKCdelta but not PKCalpha, indicating that PKCdelta played the functional role in mediating the gene activation of 12(S)-lipoxygenase induced by PMA. (PMID:11914583)
• intracellular Cl(-) (Cl) regulates the activity of protein kinase C (PKC)-delta and thus the activation of Na-K-Cl cotransport (PMID:11943682)
• PLD1 is threonine-phosphorylated in human-airway epithelial cells by a PKCdelta dependent mechanism (PMID:12014986)
• PKC delta expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox. (PMID:12056906)
• Novel isoforms regulate human keratinocyte differentiation by activating a p38 delta mitogen-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha. (PMID:12080077)
• REVIEW:Interaction of protein kinase C isozymes with membranes containing anionic phospholipids utilizing fluorescent phorbol esters to probe the properties of the C1 domains (PMID:12093536)
• contributes to apoptosis by regulating p73beta protein (PMID:12097319)
• role for the PKC-delta isoenzyme in regulating HLA class II-mediated apoptosis of mature dendritic cells (PMID:12147630)
• Data show that protein kinase C delta (PKC delta) is located downstream of RhoA and that active RhoA and PKCdelta are both necessary for leukotriene D(4)-induced stress-fibre formation. (PMID:12154081)
• Role of nuclear PKC delta in mediating caspase-3-upregulation in Jurkat T leukemic cells exposed to ionizing radiation (PMID:12210761)
• Activation is required for oxidant-induced disruption of both the microtubule cytoskeleton and permeability barrier of intestinal epithelia (PMID:12235228)
• PKC delta associates with IL6ST via Stat3 and enhances Stat3-gp130 interaction (PMID:12361954)
• PKC mediates VEGF-induced Akt activation in a novel signal transduction pathway through which Akt can be regulated by growth factors acting through receptor protein tyrosine kinases, and may play an essential role in VEGF-stimulated angiogenesis. (PMID:12377207)
• PKCdelta functions in the activation of SAPK through a Lyn –> PKCdelta –> MEKK1 –> MKK7 –> SAPK signaling cascade in response to DNA damage (PMID:12377781)
• inhibits p300 intrinsic histone acetyltransferase activity after phosphorylation at serine 89 (PMID:12379484)
• tyrosine phosphorylation and activity of PKCdelta were dependent on PI-3K activity in B-CLL cells, and survival signals might be mediated via PKCdelta (PMID:12393602)
• Down-regulation of hydrogen peroxide-induced activation of this enzyme in N-acetylglucosaminyltransferase III-transfected HeLaS3 cells (PMID:12427758)
• Protein kinase C delta-NF-kappaB signaling regulates VCAM1 stimulation by thrombin in endothelial cells (PMID:12493764)
• selective modulation of PKC delta may regulate TNF-R1 signaling in intestinal epithelium. (PMID:12505880)
• protein kinase c delta regulates apoptosis [review] (PMID:12510148)
• affects on JunB expression and monocyte differentiation (PMID:12522006)
• Il-2 and polysaccharide K increased expression of protein kinase C delta. (PMID:12536241)
• This protein is responsible for constitutive and DNA damage-induced phosphorylation of rad9 protein. (PMID:12628935)
• Phosphorylated PKCdelta, but not total PKCdelta, in dorsal root ganglion was decreased in diabetic rats. Decrease in phosphorylated PKCdelta is partly causes impaired neurite outgrowth in diabetes, and PKCdelta plays role in diabetic neuropathy. (PMID:12634498)
• PLS3 is a downstream effector of PKC-delta in the mitochondria. (PMID:12649167)
• data suggest that nuclear translocation and kinase activity of protein kinase C-delta are both necessary for saturated fatty acid-induced apoptosis (PMID:12663471)
• Data suggest that phosphorylation of protein kinase C delta may act as a negative feedback mechanism to limit the overall activation of the CD98 pathway. (PMID:12729789)
• Mediation of tumor growth factor beta-1 induced collagen I expression in glomerular mesangial cells. (PMID:12759229)
• PKC delta regulates airway epithelial cell expression of NF-kappa B-dependent proinflammatory genes IL-8, GM-CSF, RANTES, and ICAM-1. (PMID:12759450)
• The novel varepsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in the signaling pathways involved in thrombin-induced human platelet P-selectin expression (PMID:12783114)
• PKC-delta has a role in EGF protection of tumor cells from TNF-alpha-induced apoptosis (PMID:12795334)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcda	ENSDARG00000009208
danio_rerio	prkcdb	ENSDARG00000070651
mus_musculus	Prkcd	ENSMUSG00000021948
rattus_norvegicus	Prkcd	ENSRNOG00000016346

Paralogs (5): PRKCQ (ENSG00000065675), AKT2 (ENSG00000105221), AKT3 (ENSG00000117020), PDPK1 (ENSG00000140992), AKT1 (ENSG00000142208)

Protein

Protein identifiers

Protein kinase C delta type — Q05655 (reviewed: Q05655)

Alternative names: Tyrosine-protein kinase PRKCD, nPKC-delta

All UniProt accessions (8): Q05655, A0A494BZX2, A0A494C125, A0A494C1T7, A0A8V8TMH8, C9J9P1, C9JZU8, C9K0E3

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment. Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis. Phosphorylates SMPD1 which induces SMPD1 secretion.

Subunit / interactions. Interacts with PDPK1 (via N-terminal region). Interacts with RAD9A. Interacts with CDCP1. Interacts with MUC1. Interacts with VASP. Interacts with CAVIN3. Interacts with PRKD2 (via N-terminus and zing-finger domain 1 and 2) in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation. Interacts with PLSC3; interaction is enhanced by UV irradiation. Interacts with PRKCH upstream open reading frame 2; the interaction leads to inhibition of kinase activity.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus. Cell membrane. Mitochondrion. Endomembrane system.

Post-translational modifications. Autophosphorylated and/or phosphorylated at Thr-507, within the activation loop; phosphorylation at Thr-507 is not a prerequisite for enzymatic activity. Autophosphorylated at Ser-299, Ser-302 and Ser-304. Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3. Phosphorylated at Tyr-313, Tyr-334 and Tyr-567; phosphorylation of Tyr-313 and Tyr-567 following thrombin or zymosan stimulation potentiates its kinase activity. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylated at Tyr-313 through a SYK and SRC mechanism downstream of C-type lectin receptors activation, promoting its activation. Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation.

Disease relevance. Autoimmune lymphoproliferative syndrome 3 (ALPS3) [MIM:615559] A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-507 (activation loop of the kinase domain), Ser-645 (turn motif) and Ser-664 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine. Inhibited by PRKCH upstream open reading frame 2.

Domain organisation. The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor. The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner.

Miscellaneous. Antiapoptotic isoform, resistant to caspase-3 cleavage.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q05655-1	1	yes
Q05655-2	2, PKCdeltaVIII

RefSeq proteins (7): NP_001303256, NP_001341605, NP_001341607, NP_001341608, NP_001341609, NP_006245, NP_997704 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014376	Prot_kin_PKC_delta	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR027436	PKC_delta	Family
IPR034667	nPKC_delta	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00433, PF21494

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), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• 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 (69 total): modified residue 23, strand 14, sequence variant 6, site 5, chain 3, domain 3, helix 3, binding site 2, mutagenesis site 2, sequence conflict 2, turn 2, zinc finger region 2, splice variant 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1YRK	X-RAY DIFFRACTION	1.7
2YUU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05655-F1	81.29	0.46

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 (6): 48 (interaction with phosphotyrosine-containing peptide); 62 (interaction with phosphotyrosine-containing peptide); 67 (interaction with phosphotyrosine-containing peptide); 123 (interaction with phosphotyrosine-containing peptide); 329–330 (cleavage; by caspase-3); 473 (proton acceptor)

Ligand- & substrate-binding residues (2): 378; 355–363

Post-translational modifications (23): 43, 50, 64, 130, 141, 155, 218, 299, 302, 304, 307, 313, 334, 374, 451, 503, 506, 507, 567, 645 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
299	loss of phosphorylation.
507	no effect on kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

48 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-111933	Calmodulin induced events
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1489509	DAG and IP3 signaling
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-418597	G alpha (z) signalling events
R-HSA-450520	HuR (ELAVL1) binds and stabilizes mRNA
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases
R-HSA-6798695	Neutrophil degranulation
R-HSA-877300	Interferon gamma signaling
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-109581	Apoptosis
R-HSA-109582	Hemostasis
R-HSA-111885	Opioid Signalling
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-1227986	Signaling by ERBB2
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis

MSigDB gene sets: 805 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CELL_CHEMOTAXIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (46): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), DNA damage response (GO:0006974), signal transduction (GO:0007165), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), immunoglobulin mediated immune response (GO:0016064), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), termination of signal transduction (GO:0023021), negative regulation of actin filament polymerization (GO:0030837), positive regulation of superoxide anion generation (GO:0032930), regulation of actin cytoskeleton organization (GO:0032956), negative regulation of glial cell apoptotic process (GO:0034351), cellular response to UV (GO:0034644), intracellular signal transduction (GO:0035556), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), B cell proliferation (GO:0042100), neutrophil activation (GO:0042119), positive regulation of protein import into nucleus (GO:0042307), defense response to bacterium (GO:0042742), negative regulation of MAPK cascade (GO:0043409), regulation of mRNA stability (GO:0043488), positive regulation of DNA repair (GO:0045739), negative regulation of insulin receptor signaling pathway (GO:0046627), negative regulation of inflammatory response (GO:0050728), protein stabilization (GO:0050821), negative regulation of filopodium assembly (GO:0051490), cell chemotaxis (GO:0060326), cellular response to hydrogen peroxide (GO:0070301), protein kinase C signaling (GO:0070528), cellular response to fatty acid (GO:0071398), cellular response to hydroperoxide (GO:0071447), negative regulation of platelet aggregation (GO:0090331), cellular senescence (GO:0090398), phospholipase C/protein kinase C signal transduction (GO:0141212), positive regulation of phospholipid scramblase activity (GO:1900163), cellular response to angiotensin (GO:1904385), regulation of ceramide biosynthetic process (GO:2000303), positive regulation of ceramide biosynthetic process (GO:2000304), positive regulation of glucosylceramide catabolic process (GO:2000753)

GO Molecular Function (19): protein kinase activity (GO:0004672), 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), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), protein tyrosine kinase activator activity (GO:0030296), insulin receptor substrate binding (GO:0043560), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (16): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), nuclear matrix (GO:0016363), azurophil granule lumen (GO:0035578), endolysosome (GO:0036019), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
Apoptotic execution phase	1
CaM pathway	1
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Signaling by ERBB2	1
Intracellular signaling by second messengers	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
GPCR downstream signalling	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
VEGFA-VEGFR2 Pathway	1
C-type lectin receptors (CLRs)	1
RHO GTPase Effectors	1
Innate Immune System	1
Interferon Signaling	1
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
cytoplasm	4
protein kinase activity	3
intracellular membrane-bounded organelle	3
protein phosphorylation	2
intracellular anatomical structure	2
protein tyrosine kinase activity	2
catalytic activity	2
protein binding	2
nuclear lumen	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intrinsic apoptotic signaling pathway	1
B cell mediated immunity	1
peptidyl-serine modification	1
peptidyl-threonine modification	1
negative regulation of signal transduction	1
actin filament polymerization	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
regulation of superoxide anion generation	1
superoxide anion generation	1
positive regulation of reactive oxygen species metabolic process	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
glial cell apoptotic process	1
regulation of glial cell apoptotic process	1
negative regulation of apoptotic process	1

Protein interactions and networks

STRING

2888 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCD	RIPK4	P57078	893
PRKCD	CEL	P19835	801
PRKCD	STAT3	P40763	786
PRKCD	SRC	P12931	728
PRKCD	CASP3	P42574	715
PRKCD	GAB2	Q9UQC2	698
PRKCD	SYK	P43405	694
PRKCD	SHC1	P29353	692
PRKCD	HSP90AA1	P07900	686
PRKCD	CDCP1	Q9H5V8	678
PRKCD	CAVIN3	Q969G5	678
PRKCD	CYCS	P00001	661
PRKCD	DVL1	O14640	655
PRKCD	RACK1	P25388	611
PRKCD	CTNNB1	P35222	611

IntAct

125 interactions, top by confidence:

A	B	Type	Score
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
PRKCD	FYN	psi-mi:“MI:0915”(physical association)	0.740
PRKCD	FYN	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
FYN	PRKCD	psi-mi:“MI:2364”(proximity)	0.740
FYN	PRKCD	psi-mi:“MI:0915”(physical association)	0.740
PRKCD	IL32	psi-mi:“MI:0403”(colocalization)	0.730
IL32	PRKCD	psi-mi:“MI:0915”(physical association)	0.730
PRKCD	IL32	psi-mi:“MI:0915”(physical association)	0.730
TOP2A	PRKCD	psi-mi:“MI:0915”(physical association)	0.680
PRKCD	TOP2A	psi-mi:“MI:0915”(physical association)	0.680
PRKCD	TOP2A	psi-mi:“MI:0914”(association)	0.680
PRKCD	TOP2A	psi-mi:“MI:0407”(direct interaction)	0.680
PRKCD	TOP2A	psi-mi:“MI:0217”(phosphorylation reaction)	0.680
CDCP1	PRKCD	psi-mi:“MI:0403”(colocalization)	0.670
CDCP1	PRKCD	psi-mi:“MI:0915”(physical association)	0.670
PRKCD	CDCP1	psi-mi:“MI:0915”(physical association)	0.670
CARD11	PRKCD	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (273): PRKCD (Affinity Capture-Western), EP300 (Biochemical Activity), FLI1 (Biochemical Activity), PRKCD (Affinity Capture-Western), DIABLO (Affinity Capture-Western), PRKCD (Affinity Capture-Western), PTGES3 (Co-fractionation), PRKCD (Synthetic Lethality), DAB2 (Biochemical Activity), RPL37A (Affinity Capture-MS), TKT (Affinity Capture-MS), ZNF131 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), DHX16 (Affinity Capture-MS), PRPF4B (Affinity Capture-MS)

ESM2 similar proteins: A0A2I0BVG8, A0A509AHB6, A0A509AKL0, A5K0N4, A8X6H1, A8X6H4, A8XNJ6, O15865, O61267, O64629, O94737, P05130, P07278, P09215, P21901, P23298, P24723, P28867, P42680, P54644, P62343, P62344, P62345, P81900, P90980, Q05655, Q13237, Q26619, Q2PJ68, Q54CY9, Q54QB1, Q55GV3, Q5BKK4, Q5F3L1, Q5PU49, Q61410, Q64595, Q64617, Q6GLY8, Q6GPN6

Diamond homologs: A0JNJ1, A1CEK6, A1DFN5, A2QW93, A4RF61, A6QLK6, A7A261, F1LRS8, O35179, O35964, O43307, O74749, O75791, O75886, O88811, O89100, O93436, P02549, P07751, P09215, P09216, P10830, P13395, P16054, P16086, P16546, P23298, P24723, P28867, P29355, P32793, P34885, P38753, P43603, P53281, P62993, P62994, P70297, P87379, P97306

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
PTPN1	down-regulates	PRKCD	dephosphorylation
PRKCD	“up-regulates activity”	ITGB2	phosphorylation
PRKCD	up-regulates	MUC1	phosphorylation
PRKCD	down-regulates	GSK3A	phosphorylation
PRKCD	up-regulates	PEBP1	phosphorylation
PRKCD	up-regulates	PRKD1	phosphorylation
PRKCD	down-regulates	IRS1	phosphorylation
PRKCD	“down-regulates activity”	IRS1	phosphorylation
PRKCD	down-regulates	DAB2	phosphorylation
PRKCD	up-regulates	PRKCD	phosphorylation
PRKCD	down-regulates	LIMK2	phosphorylation
PRKCD	up-regulates	RPS3	phosphorylation
PRKCD	down-regulates	YWHAB	phosphorylation
PRKCD	up-regulates	PLSCR3	phosphorylation
PRKCD	up-regulates	TP53	phosphorylation
PRKCD	up-regulates	STAT3	phosphorylation
PRKCD	up-regulates	SHC1	phosphorylation
PRKCD	unknown	SHC1	phosphorylation
PRKCD	up-regulates	MYBPC3	phosphorylation
PRKCD	down-regulates	C5AR1	phosphorylation
PRKCD	up-regulates	MAPK8	phosphorylation
PRKCD	up-regulates	DNM1L	phosphorylation
PRKCD	up-regulates	SMPD1	phosphorylation
PRKCD	up-regulates	STAT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
VEGFA-VEGFR2 Pathway	7	17.1×	1e-04
Transcriptional regulation by RUNX1	5	12.8×	4e-03
CLEC7A (Dectin-1) signaling	5	12.5×	4e-03
Downstream TCR signaling	5	11.3×	6e-03
RHOA GTPase cycle	6	7.9×	6e-03
RHO GTPase Effectors	6	7.2×	7e-03
Signaling by Receptor Tyrosine Kinases	7	6.3×	6e-03
Axon guidance	7	5.5×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
T cell receptor signaling pathway	5	10.7×	9e-03
negative regulation of gene expression	8	7.8×	2e-03
DNA damage response	10	7.5×	7e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — NHL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	7
Uncertain significance	213
Likely benign	267
Benign	56

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1070386	NC_000003.11:g.(?53125899)(53226302_?)del	Pathogenic
1072331	NM_006254.4(PRKCD):c.1301del (p.Asp434fs)	Pathogenic
1320322	NM_006254.4(PRKCD):c.571+2dup	Pathogenic
1320323	NM_006254.4(PRKCD):c.1384C>T (p.Gln462Ter)	Pathogenic
1320324	NM_006254.4(PRKCD):c.642del (p.Asn214fs)	Pathogenic
1454573	NM_006254.4(PRKCD):c.285C>A (p.Cys95Ter)	Pathogenic
1458167	NM_006254.4(PRKCD):c.1300dup (p.Asp434fs)	Pathogenic
157674	NM_006254.4(PRKCD):c.1528G>A (p.Gly510Ser)	Pathogenic
2128407	NM_006254.4(PRKCD):c.1182del (p.Met395fs)	Pathogenic
3650412	NM_006254.4(PRKCD):c.1542T>G (p.Tyr514Ter)	Pathogenic
4713023	NM_006254.4(PRKCD):c.1318C>T (p.Gln440Ter)	Pathogenic
89076	NM_006254.4(PRKCD):c.1352+1G>A	Pathogenic
958249	NM_006254.4(PRKCD):c.571C>T (p.Gln191Ter)	Pathogenic
2028257	NM_006254.4(PRKCD):c.1743+2T>A	Likely pathogenic
2068571	NM_006254.4(PRKCD):c.788-1G>T	Likely pathogenic
2909516	NM_006254.4(PRKCD):c.571+1G>A	Likely pathogenic
3391052	NM_006254.4(PRKCD):c.1073G>A (p.Gly358Asp)	Likely pathogenic
3652522	NM_006254.4(PRKCD):c.657+1G>A	Likely pathogenic
4845698	NM_006254.4(PRKCD):c.769C>T (p.Gln257Ter)	Likely pathogenic
541623	NM_006254.4(PRKCD):c.788-2A>G	Likely pathogenic

SpliceAI

2724 predictions. Top by Δscore:

Variant	Effect	Δscore
3:53161424:GGGAG:G	donor_gain	1.0000
3:53161425:GGAGG:G	donor_gain	1.0000
3:53178535:CAGG:C	donor_loss	1.0000
3:53178537:GGTA:G	donor_loss	1.0000
3:53178538:GTA:G	donor_loss	1.0000
3:53178539:T:A	donor_loss	1.0000
3:53179572:T:A	acceptor_gain	1.0000
3:53179572:TGCA:T	acceptor_loss	1.0000
3:53179573:GCAG:G	acceptor_loss	1.0000
3:53179574:CAG:C	acceptor_gain	1.0000
3:53179575:A:AG	acceptor_gain	1.0000
3:53179575:AG:A	acceptor_loss	1.0000
3:53179575:AGA:A	acceptor_gain	1.0000
3:53179575:AGAGC:A	acceptor_gain	1.0000
3:53179576:G:GA	acceptor_gain	1.0000
3:53179576:GA:G	acceptor_gain	1.0000
3:53179576:GAG:G	acceptor_gain	1.0000
3:53179576:GAGC:G	acceptor_gain	1.0000
3:53179576:GAGCG:G	acceptor_gain	1.0000
3:53179765:GC:G	donor_gain	1.0000
3:53179766:C:G	donor_gain	1.0000
3:53179774:TGGGT:T	donor_loss	1.0000
3:53179775:GG:G	donor_gain	1.0000
3:53179776:GG:G	donor_gain	1.0000
3:53179777:G:GC	donor_loss	1.0000
3:53179777:G:GG	donor_gain	1.0000
3:53179778:T:A	donor_loss	1.0000
3:53181187:T:A	acceptor_gain	1.0000
3:53181188:G:A	acceptor_gain	1.0000
3:53181194:T:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000234770 (3:53164320 C>T), RS1000565700 (3:53164578 G>A), RS1000614219 (3:53182544 T>C), RS1000642261 (3:53170452 G>A), RS1000694818 (3:53170094 A>C), RS1000809454 (3:53176423 C>T), RS1001110018 (3:53188255 C>G,T), RS1001491598 (3:53193045 C>T), RS1001528686 (3:53187913 G>A), RS1001545607 (3:53169730 G>A), RS1001735042 (3:53163928 T>C), RS1001955931 (3:53187548 C>G), RS1001996490 (3:53169408 G>A), RS1002142823 (3:53181975 T>C), RS1002631746 (3:53184568 A>G,T)

Disease associations

OMIM: gene MIM:176977 | disease phenotypes: MIM:615559

GenCC curated gene-disease

Disease	Classification	Inheritance
autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD	Strong	Autosomal recessive
common variable immunodeficiency	Supportive	Autosomal dominant
autosomal systemic lupus erythematosus type 16	Supportive	Autosomal dominant
autoimmune lymphoproliferative syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
systemic lupus erythematosus	Definitive	AR

Mondo (4): autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD (MONDO:8000024), common variable immunodeficiency (MONDO:0015517), autosomal systemic lupus erythematosus type 16 (MONDO:0013743), autoimmune lymphoproliferative syndrome (MONDO:0017979)

Orphanet (2): Autoimmune lymphoproliferative syndrome (Orphanet:3261), EBV-induced lymphoproliferative disease due to PRKCD deficiency (Orphanet:664711)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000100	Nephrotic syndrome
HP:0000403	Recurrent otitis media
HP:0001369	Arthritis
HP:0001433	Hepatosplenomegaly
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001890	Autoimmune hemolytic anemia
HP:0001954	Recurrent fever
HP:0001973	Autoimmune thrombocytopenia
HP:0002240	Hepatomegaly
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002729	Follicular hyperplasia
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002960	Autoimmunity
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003774	Stage 5 chronic kidney disease
HP:0005404	Increased total B cell count
HP:0005421	Decreased circulating complement C3 concentration
HP:0005523	Lymphoproliferative disorder
HP:0008940	Generalized lymphadenopathy
HP:0010702	Increased circulating immunoglobulin concentration
HP:0011108	Recurrent sinusitis
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012177	Abnormal natural killer cell physiology
HP:0012578	Membranous nephropathy

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001241_15	Bipolar disorder	2.000000e-06
GCST001728_7	Ulcerative colitis	1.000000e-08
GCST006396_5	Disrupted circadian rhythm (low relative amplitude of rest-activity cycles)	4.000000e-07
GCST008161_34	Waist circumference adjusted for body mass index	8.000000e-07
GCST90020024_1218	A body shape index	5.000000e-10
GCST90020025_1352	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020025_1353	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_150	Waist-hip index	2.000000e-08
GCST90020027_251	Waist-hip index	2.000000e-08
GCST90020029_1203	Waist circumference adjusted for body mass index	4.000000e-08
GCST90020029_1204	Waist circumference adjusted for body mass index	6.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D056735	Autoimmune Lymphoproliferative Syndrome	C15.604.515.138; C16.320.089; C20.111.288; C20.683.515.124
D017074	Common Variable Immunodeficiency	C20.673.330

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL2996 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

49 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 403,740 (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
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1667969	SAR-407899 FREE BASE	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL2386889	SCH-900776	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Delta subfamily

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.42	pKi
bryostatin 1	Activation	9.36	pKi
10-Me-Aplog-1	Activation	9.34	pKi
sotrastaurin	Inhibition	8.89	pIC50
Gö 6983	Inhibition	8.0	pIC50
balanol	Inhibition	7.8	pIC50
compound 23 [PMID: 35816678]	Inhibition	7.15	pIC50
ruboxistaurin	Inhibition	6.6	pIC50
7-hydroxystaurosporine	Inhibition	6.23	pIC50
enzastaurin	Inhibition	6.0	pIC50
rottlerin	Inhibition	5.52	pIC50
CC-90005	Inhibition	5.35	pIC50

Binding affinities (BindingDB)

141 measured of 166 human assays (167 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
[(1S,4S,5S,6R,9S,10S,12R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11-trimethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.1 nM	US-9409931: 3-O-acyl-ingenol analogues
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
[(4R,5R,6S,9S,10S,12R,14R)-6-hydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.2 nM	US-9409931: 3-O-acyl-ingenol analogues
CHEMBL4435580	IC50	0.22 nM
NSC_4179	KI	0.27 nM
Butyric acid (1aS,1bS,4aS,7aS,8R,9S,9aR)-9-butyryloxy-4a,7b-dihydroxy-3-((R)-hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl ester	KD	0.28 nM
NSC_6437389	KI	0.29 nM
NSC_105100	KI	0.35 nM
CHEMBL4587471	IC50	0.36 nM
Bryostatin	KD	0.44 nM
CAS_159320	KI	0.45 nM
CHEMBL4575056	EC50	0.6 nM
bryostatin 1	KD	0.73 nM
[(1S,4S,5R,9S,10S,12R,14R)-5-hydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.8 nM	US-9409931: 3-O-acyl-ingenol analogues
maleimide derivative, 12	IC50	0.9 nM
Staurosporine	KD	1.7 nM
AEB071	IC50	2.1 nM
maleimide derivative, 10	IC50	2.2 nM
2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl)maleimide	IC50	2.3 nM
5-vinyl-3-pyridinecarbonitrile, 12b	IC50	2.5 nM
5-vinyl-3-pyridinecarbonitrile, 37	IC50	3.4 nM
Phorbol ester (PDBU)	KD	3.4 nM
5-vinyl-3-pyridinecarbonitrile, 14b	IC50	5.8 nM
[(1S,4R,5S,9S,10S,12R,14R)-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	6 nM	US-9409931: 3-O-acyl-ingenol analogues
maleimide derivative, 11	IC50	7.1 nM
5-vinyl-3-pyridinecarbonitrile, 14a	IC50	8 nM
B8-DL-B8 (low PS)	KI	10.8 nM
CAS_454217	KI	12.9 nM
maleimide derivative, 9	IC50	15 nM
5-vinyl-3-pyridinecarbonitrile, 22	IC50	15 nM
5-vinyl-3-pyridinecarbonitrile, 13b	IC50	16 nM
5-vinyl-3-pyridinecarbonitrile, 14c	IC50	18 nM
5-vinyl-3-pyridinecarbonitrile, 23	IC50	18 nM
Sapintoxin D	KI	18.2 nM
2-{[2,6-dihydroxy-4-({[(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	22 nM
5-vinyl-3-pyridinecarbonitrile, 13a	IC50	22 nM
5-vinyl-3-pyridinecarbonitrile, 19	IC50	26 nM
5-vinyl-3-pyridinecarbonitrile, 13c	IC50	27 nM
5-vinyl-3-pyridinecarbonitrile, 16	IC50	28 nM
5-vinyl-3-pyridinecarbonitrile, 20	IC50	29 nM
2-{[2,6-dihydroxy-4-({[(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	30 nM
5-vinyl-3-pyridinecarbonitrile, 18	IC50	33 nM
(-)-Indolactam V (low PS)	KI	38 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	40 nM
2-({2,6-dihydroxy-4-[({2-[(4-hydroxybenzene)amido]cyclopentyl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	40 nM
5-vinyl-3-pyridinecarbonitrile, 12a	IC50	43 nM

ChEMBL bioactivities

1363 potent at pChembl≥5 of 1495 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
10.00	IC50	0.1	nM	CHEMBL2151411
9.96	Ki	0.11	nM	CHEMBL5172923
9.89	IC50	0.128	nM	STAUROSPORINE
9.89	IC50	0.13	nM	CHEMBL3741746
9.89	IC50	0.129	nM	STAUROSPORINE
9.89	Kd	0.129	nM	CHEMBL5653589
9.87	ED50	0.136	nM	CHEMBL5653589
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
9.71	Kd	0.193	nM	CHEMBL27768
9.71	IC50	0.193	nM	STAUROSPORINE
9.70	Ki	0.2	nM	DEBROMOAPLYSIATOXIN
9.66	IC50	0.22	nM	CHEMBL4435580
9.49	Ki	0.32	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
9.49	Ki	0.32	nM	CHEMBL417692
9.44	IC50	0.36	nM	CHEMBL4587471
9.40	IC50	0.4	nM	CHEMBL1996510
9.39	Ki	0.41	nM	APLYSIATOXIN
9.36	Ki	0.44	nM	BRYOSTATIN 1
9.34	Ki	0.46	nM	CHEMBL2148108
9.34	Ki	0.46	nM	CHEMBL399981
9.28	Kd	0.53	nM	CHEMBL27768
9.26	EC50	0.55	nM	CHEMBL4587471
9.26	Ki	0.55	nM	CHEMBL265998
9.22	IC50	0.6	nM	CHEMBL2153750
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.10	Ki	0.8	nM	PHORBOL MYRISTATE ACETATE
9.10	Ki	0.8	nM	CHEMBL160375
9.10	Ki	0.8	nM	CHEMBL159233
9.10	Ki	0.8	nM	CHEMBL351103
9.10	Ki	0.8	nM	CHEMBL27768
9.10	Ki	0.8	nM	CHEMBL285801
9.05	IC50	0.9	nM	CHEMBL427118
9.05	IC50	0.9	nM	CHEMBL52529
9.05	Ki	0.9	nM	CHEMBL137386
9.05	IC50	0.9	nM	CHEMBL48636
9.00	IC50	1	nM	CHEMBL2151415
9.00	Kd	1	nM	CHEMBL27768
9.00	IC50	1	nM	CHEMBL48636
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL52529
9.00	IC50	1	nM	CHEMBL71331
9.00	Kd	1	nM	CHEMBL337834
8.99	Ki	1.03	nM	CHEMBL27768

PubChem BioAssay actives

983 with measured affinity, of 2993 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149078: Binding affinity to human PRKCD incubated for 45 mins by Kinobead based pull down assay	kd	0.0001	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-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	1531839: Inhibition of human PKCdelta using ERMRPRKRQGSVRRRV as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0001	uM
(10S,13S)-5-[(3R)-3,7-dimethylocta-1,6-dien-3-yl]-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4,6,8(15)-tetraen-11-one	1942299: Inhibition of [3H]-PDBu binding to PKCdelta C1B domain (unknown origin) by competitive binding assay	ki	0.0001	uM
[(1R,6R,13R,14R,15S)-13-butanoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5,8-dioxo-14-tetracyclo[8.5.0.02,6.011,13]pentadec-3-enyl] 2-(methylamino)benzoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	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] 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
[(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
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-butanoyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	1138942: Binding affinity to PKC-delta C1B domain (unknown origin)	kd	0.0002	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S,5S)-5-(3-hydroxyphenyl)-5-methoxypentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687832: Inhibition of [3H]PDBu binding to PKCdelta C1B domain	ki	0.0002	uM
[(1R,6R,13R,14R,15S)-13-butanoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5,8-dioxo-14-tetracyclo[8.5.0.02,6.011,13]pentadec-3-enyl] butanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	kd	0.0002	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S)-5-(3-hydroxyphenyl)pentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	768063: Displacement of [3H]PDBu from PKCdelta C1B domain (unknown origin)	ki	0.0003	uM
(6S,9S,14R,17R)-17-ethenyl-6-(hydroxymethyl)-10,14,17-trimethyl-9,14-di(propan-2-yl)-2,7,10-triazatetracyclo[9.7.1.04,19.013,18]nonadeca-1(18),3,11(19),12-tetraen-8-one	163528: Displacement of [3H]PDBu from recombinant Protein kinase C delta	ki	0.0003	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0004	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
(1S,3R,4S,5S,9R,13S,14R)-3-[(2S,5S)-5-(2-bromo-5-hydroxyphenyl)-5-methoxypentan-2-yl]-13-hydroxy-9-[(1R)-1-hydroxyethyl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	517266: Inhibition of [3H]PDBu binding to PKC delta C1B peptide	ki	0.0004	uM
[(1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,21R,23R,25S)-25-acetyloxy-1,11,21-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl] (2E,4E)-octa-2,4-dienoate	374768: Displacement of [3H]PDBu from human recombinant PKCdelta expressed in Sf9 cells by liquid scintillation counting	ki	0.0004	uM
(10S,13S)-3-hexyl-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4(15),5,7-tetraen-11-one	312187: Displacement of [3H]PDBu from PKCdelta C1B domain	ki	0.0005	uM
(1R,3R,4R,5S,9R,13R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-4,16,16-trimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687832: Inhibition of [3H]PDBu binding to PKCdelta C1B domain	ki	0.0005	uM
[(1R,2R,6S,10S,11R,13S,14R,15R)-13-butanoyloxy-1-hydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	163680: Displacement of 3[H]PDBu from Protein kinase C delta C1b domain	ki	0.0006	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0006	uM
(2S,5S)-2-decyl-5-(hydroxymethyl)-1-methyl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	155742: Binding affinity for human recombinant protein kinase C delta	ki	0.0008	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-5-octyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4,6,8(15)-tetraen-11-one	163526: Displacement of [3H]- PDBu from recombinant PKC delta expressed in baculovirus	ki	0.0008	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate	220518: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C delta	ki	0.0008	uM
(2S,5S)-5-(hydroxymethyl)-1-methyl-2-tetradecyl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	155742: Binding affinity for human recombinant protein kinase C delta	ki	0.0008	uM
(2S,5S)-2-dodecyl-5-(hydroxymethyl)-1-methyl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	155742: Binding affinity for human recombinant protein kinase C delta	ki	0.0008	uM
2-[2,6-dihydroxy-4-[2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163378: Evaluated against recombinant human Protein kinase C delta	ic50	0.0009	uM
[(4E)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	238839: Binding affinity for isolated C1b domain of protein kinase C-delta	ki	0.0009	uM
N-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-8-yl]-N’-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-9-yl]tetradecanediamide	163510: Binding affinity for human Protein kinase C delta	kd	0.0010	uM
2-[2,6-dihydroxy-4-[(1R,2R)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163505: Inhibitory concentration against recombinant human Protein kinase C delta isozyme	ic50	0.0010	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0010	uM
3-[6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0012	uM
[(4Z)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	0.0012	uM
[(1S,17R,19S,21E,22S)-8-(2,6-dimethoxyphenyl)-1-hydroxy-17-(hydroxymethyl)-21-(2-methoxy-2-oxoethylidene)-2,2-dimethyl-5,15-dioxo-4,12,16,23-tetraoxatricyclo[17.3.1.06,11]tricosa-6(11),7,9-trien-22-yl] octanoate	1634646: Inhibition of [3H]PDBu binding to recombinant full length human PKCdelta expressed in baculovirus expression system incubated for 5 mins by scintillation counting method	ki	0.0013	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1437219: Inhibition of PKCdelta (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0013	uM
(1S,3R,5R,9R,13R)-3-[4-(3-hydroxy-4-iodophenyl)butyl]-9-(hydroxymethyl)-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	746975: Inhibition of [3H]PDBu binding to PKCdelta-C1B domain peptide (unknown origin)	ki	0.0013	uM
[(4E)-2-(hydroxymethyl)-4-[(4-hydroxyphenyl)methylidene]-5-oxooxolan-2-yl]methyl 4-methyl-3-propan-2-ylpentanoate	265548: Binding affinity to PKCdeltaC1b in presence of phospholipid	ki	0.0014	uM
[(4Z)-4-[[4-(dimethylamino)phenyl]methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 4-nitrobenzoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	0.0015	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
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0018	uM
(2S,5S)-9-decyl-5-(hydroxymethyl)-1-methyl-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	163511: Displacement of [3H]-PDBu from human recombinant Protein kinase C delta	ki	0.0018	uM
[(1S,17R,19S,21E,22S)-8-[2,6-di(propan-2-yloxy)phenyl]-1-hydroxy-17-(hydroxymethyl)-21-(2-methoxy-2-oxoethylidene)-2,2-dimethyl-5,15-dioxo-4,12,16,23-tetraoxatricyclo[17.3.1.06,11]tricosa-6(11),7,9-trien-22-yl] octanoate	1634646: Inhibition of [3H]PDBu binding to recombinant full length human PKCdelta expressed in baculovirus expression system incubated for 5 mins by scintillation counting method	ki	0.0019	uM
[(1R,3S,7S,8E,11S,12S,13E,17R,21R,23S)-11,21-dihydroxy-17-[(1R)-1-hydroxyethyl]-13-(2-methoxy-2-oxoethylidene)-10,10-dimethyl-19-oxo-6,18,27,28,29-pentaoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl] octanoate	163677: Displacement of [3H]PDBu from protein kinase C delta C1b domain	ki	0.0025	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-4-(4-methylpiperazin-1-yl)but-1-enyl]pyridine-3-carbonitrile	1799293: PKC IMAP Kinase Assay from Article 10.1016/j.bmc.2009.10.020: “5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCtheta: optimization of enzymatic and functional activity.”	ic50	0.0025	uM
3-(5-chloro-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690000: Inhibition of PKCdelta by scintillation proximity assay	ic50	0.0025	uM
[(1S,4S,5S,6R,9S,10R,12R,14R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 2-(methylamino)benzoate	1063167: Activation of PKCdelta (unknown origin) after 40 mins	ec50	0.0025	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	decreases activity, increases expression, increases localization, affects reaction, decreases reaction (+8 more)	18
rottlerin	increases phosphorylation, increases activity, increases cleavage, decreases activity, increases expression (+3 more)	8
Tretinoin	increases activity, affects expression, affects cotreatment, decreases expression, decreases reaction (+2 more)	7
sodium arsenite	decreases reaction, decreases phosphorylation, increases reaction, increases phosphorylation, decreases expression (+2 more)	6
Quercetin	affects localization, decreases reaction, increases phosphorylation, increases activity, increases localization (+2 more)	4
bisindolylmaleimide I	decreases reaction, increases expression, decreases expression, affects phosphorylation, affects reaction	3
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases activity, increases cleavage, increases reaction, increases ubiquitination, increases phosphorylation (+1 more)	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, decreases reaction, increases phosphorylation, increases activity, increases localization (+2 more)	3
Curcumin	increases phosphorylation, increases reaction, increases expression, affects reaction, decreases reaction	3
Estradiol	affects cotreatment, decreases expression	3
diphenyleneiodonium	affects localization, decreases reaction, increases localization	2
bisphenol B	decreases expression, increases expression	2
NSC606985	increases activity, increases cleavage, increases reaction, affects reaction, decreases expression (+1 more)	2
Bortezomib	affects cotreatment, increases activity, increases cleavage, increases reaction	2
Wortmannin	increases phosphorylation, increases activity, increases localization, decreases reaction	2
Arsenic Trioxide	increases activity, increases cleavage, affects cotreatment	2
Acetylcysteine	decreases reaction, increases phosphorylation, increases localization	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Doxorubicin	increases reaction, increases activity, increases response to substance, decreases reaction, increases cleavage	2
Glutathione	decreases reaction, increases phosphorylation	2
Plant Extracts	affects cotreatment, increases expression, increases activity	2
1-Methyl-4-phenylpyridinium	decreases expression, increases expression	2
Aflatoxin B1	increases expression	2
FR900359	affects phosphorylation	1
daidzein	decreases expression	1
triphenyl phosphate	affects expression	1
2-amino-4-hydroxy-6-formylpteridine	affects localization	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
2-butenal	increases expression, increases reaction	1

ChEMBL screening assays

804 unique, capped per target: 790 binding, 14 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

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C5	Abcam HeLa PRKCD KO	Cancer cell line	Female
CVCL_B3EV	Abcam HEK293T PRKCD KO	Transformed cell line	Female
CVCL_D1U3	Abcam U-87MG PRKCD KO	Cancer cell line	Male
CVCL_TG82	HAP1 PRKCD (-) 1	Cancer cell line	Male
CVCL_TG83	HAP1 PRKCD (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT01489618	PHASE2	TERMINATED	Prime Boost Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02579967	PHASE2	RECRUITING	Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
NCT03663933	PHASE2	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation
NCT04339777	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
NCT04925375	PHASE2	RECRUITING	Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
NCT05593588	PHASE2	ENROLLING_BY_INVITATION	Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency
NCT06897358	PHASE2	ACTIVE_NOT_RECRUITING	Leniolisib for Immune Dysregulation in CVID
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT06730126	PHASE2	RECRUITING	Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients
NCT00263237	PHASE1	COMPLETED	STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT00004695	Not specified	COMPLETED	Randomized Study of Polyethylene-Glycol-Conjugated Interleukin 2 in Patients With Common Variable Immunodeficiency
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00015431	Not specified	COMPLETED	Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
NCT00661401	Not specified	COMPLETED	Specific IgG Antibody in Patients With Primary Antibody Deficiencies Treated With Subcutaneous Immunoglobulin
NCT00943514	Not specified	RECRUITING	Natural History of Bronchiectasis
NCT01196702	Not specified	COMPLETED	Lymphocyte Immunophenotyping in Common Variable Immunodeficiency
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01981785	Not specified	UNKNOWN	Investigation of Immune Disorders and Deficiencies
NCT02960399	Not specified	TERMINATED	Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
NCT03188419	Not specified	COMPLETED	Breadth of Donor Options for People With Inherited Diseases Requiring Allogeneic Hematopoietic Stem Cell Transplant in the Era of Alternative Donor Transplants Using Post-Transplantation Cyclophosphamide
NCT03211689	Not specified	COMPLETED	The Impact of Exercise on Stress, Fatigue, and Quality of Life in Individuals With Primary Immunodeficiency Disease
NCT03534479	Not specified	COMPLETED	Human IgGs and Endothelial Function in Vivo in Humans
NCT05310604	Not specified	COMPLETED	Early Detection of Primary Antibody Deficiencies in Primary Care Facilities by an Algorithm Driven Selection of Serologic Testing in Individuals at Risk.
NCT05321407	Not specified	ACTIVE_NOT_RECRUITING	COVID-19 Vaccine Responses in PIDD Subjects
NCT05481554	Not specified	UNKNOWN	Composition and Function of Gut Microbiota in Porto-sinusoidal Vascular Disease Associated With Variable Common Immunodeficiency