PRKCG

Summary

PRKCG (protein kinase C gamma, HGNC:9402) is a protein-coding gene on chromosome 19q13.42, encoding Protein kinase C gamma type (P05129). Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functio….

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5582 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 14 (Definitive, GenCC)
• Clinical variants (ClinVar): 382 total — 20 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002739

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9402
Approved symbol	PRKCG
Name	protein kinase C gamma
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	PKCC, MGC57564, PKCγ
Ensembl gene	ENSG00000126583
Ensembl biotype	protein_coding
OMIM	176980
Entrez	5582

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000263431, ENST00000419486, ENST00000474397, ENST00000479081, ENST00000682028, ENST00000682268, ENST00000682676, ENST00000682902, ENST00000683513

RefSeq mRNA: 2 — MANE Select: NM_002739 NM_001316329, NM_002739

CCDS: CCDS12867, CCDS92683

Canonical transcript exons

ENST00000263431 — 18 exons

Exon	Start	End
ENSE00000724715	53892509	53892643
ENSE00000724731	53892988	53893075
ENSE00000895287	53906317	53906457
ENSE00000895297	53900611	53900749
ENSE00000895298	53900419	53900481
ENSE00000895299	53900233	53900324
ENSE00000895302	53898440	53898628
ENSE00000954002	53906707	53907652
ENSE00001245692	53891674	53891830
ENSE00001245754	53882197	53882664
ENSE00001245768	53904635	53904742
ENSE00001744994	53903073	53903153
ENSE00003013572	53889886	53890017
ENSE00003527101	53884161	53884243
ENSE00003546867	53883163	53883194
ENSE00003583896	53897959	53898111
ENSE00003607622	53893362	53893391
ENSE00003672181	53889638	53889749

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 93.11.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2837 / max 370.9603, expressed in 283 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177427	3.6096	276
177428	0.4306	88
177429	0.1855	66
208920	0.0580	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	93.11	gold quality
nucleus accumbens	UBERON:0001882	92.75	gold quality
prefrontal cortex	UBERON:0000451	91.76	gold quality
amygdala	UBERON:0001876	89.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.50	gold quality
cingulate cortex	UBERON:0003027	89.15	gold quality
anterior cingulate cortex	UBERON:0009835	88.93	gold quality
caudate nucleus	UBERON:0001873	88.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.29	gold quality
frontal cortex	UBERON:0001870	87.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.30	gold quality
Ammon’s horn	UBERON:0001954	87.07	gold quality
oocyte	CL:0000023	86.66	gold quality
neocortex	UBERON:0001950	86.44	gold quality
temporal lobe	UBERON:0001871	85.65	gold quality
telencephalon	UBERON:0001893	85.40	gold quality
cerebral cortex	UBERON:0000956	85.30	gold quality
putamen	UBERON:0001874	84.99	gold quality
cerebellar cortex	UBERON:0002129	83.62	gold quality
cerebellar hemisphere	UBERON:0002245	83.62	gold quality
entorhinal cortex	UBERON:0002728	82.62	gold quality
forebrain	UBERON:0001890	82.02	gold quality
cerebellum	UBERON:0002037	81.28	gold quality
brain	UBERON:0000955	80.75	gold quality
superior frontal gyrus	UBERON:0002661	80.54	gold quality
central nervous system	UBERON:0001017	80.06	gold quality
secondary oocyte	CL:0000655	79.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.99	gold quality
postcentral gyrus	UBERON:0002581	74.54	gold quality
hypothalamus	UBERON:0001898	74.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, EGR1, FOS, HR, IRF1, JUN, MYC, NFATC2, NFKB, NKX2-2, NR3C1, NR5A1, PDX1, PITX2, RELA, SP1, SP3, STAT3, TFAP2A, TP53, TXK, ZHX2

miRNA regulators (miRDB)

81 targeting PRKCG, 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-3925-3P	100.00	69.95	1237
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-646	99.68	67.84	1645

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• Missense mutations occur in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia. (PMID:12644968)
• the affinity of isolated C1A and C1B domains of PKCalpha and PKCgamma for soluble and membrane-incorporated DAG and phorbol ester were measured by isothermal calorimetry and surface plasmon resonance in order to compare activation mechanisms (PMID:12954613)
• activation of mGluR5 causes translocation of both gammaPKC and deltaPKC to the plasma membrane. deltaPKC, but not gammaPKC, phosphorylates mGluR5 Thr(840), leading to the blockade of both Ca2+ oscillations and gammaPKC cycling. (PMID:14561742)
• Spinocerebellar ataxia(SCA) type 14 is caused by mutations in PRKCG gene. The observation that all 4 PRKCG mutations identified in patients with SCA to date are located in exon 4 suggests a critical role for this region of the gene in cerebellar function. (PMID:14676051)
• We sequenced exons 4 and 5 of PRKCG and detected a missense mutation in exon 4, involving a G–>A transition in nucleotide 353 and resulting in a glycine-to-aspartic acid substitution at residue 118 in a Dutch autosomal dominant cerebellar ataxia family (PMID:14694043)
• osmotic shock in human keratinocytes leads to activation of phospholipase C-gamma1 (PMID:15014953)
• A novel missense mutation, F643L, which maps to a highly conserved amino acid of the catalytic domain of protein kinase C gamma, extends the phenotype associated with the spinocerebellar ataxia type 14 (SCA14) locus. (PMID:15313841)
• spinocerebellar ataxia type 14 mutations make gammaPKC form cytoplasmic aggregates, which may play a role in development of SCA14 (PMID:15964845)
• Six mutations were found that segregated with the disease including F643L (exon 18), Five new missense mutations were identified in exons 4 (C114Y/G123R/G123E), 10 (G360S) and 18 (V692G). (PMID:16193476)
• These results indicate that PKCgamma regulates NMHC-IIB phosphorylation and cellular localization in response to EGF stimulation. (PMID:16394101)
• These results suggest that the PKC gamma R659S mutation is susceptible to neuronal death and is involved in the pathogenesis of neurodegenerative diseases, including Retinitis pigmentosa. (PMID:16828200)
• The present findings show that the interaction between PKCgamma and GluR4 is specifically required to assure PKC-driven phosphorylation and surface membrane expression of GluR4. (PMID:17233759)
• PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype. (PMID:17343273)
• detection of a new mutation in PRKCG responsible for spinocerebellar ataxia type 14, which may be located in a mutational hot spot (PMID:17562946)
• Codon 101 of PRKCG, a preferential mutation site in SCA14. (PMID:17659643)
• This study present a benign SCA14 phenotype in a German patient associated with a missense mutation in exon 3 of the PRKCG gene (PMID:17708558)
• PKCgamma, but not C1 domain mutants, inhibits Ca2+ influx in response to muscarinic receptor stimulation. (PMID:18499672)
• These studies suggest that Purkinje cell damage in SCA14 may result from a reduction of PKCgamma activity due its aberrant sequestration in the early endosome compartment. (PMID:18503760)
• The impact of three C1B regulatory subdomain mutations on the intracellular kinetics, protein conformation and kinase activity of PKCgamma in living cells, was investigated. (PMID:18577575)
• Rac regulates the interaction of fascin with active PKC. (PMID:18716283)
• study investigated whether mutant gammaPKC formed aggregates and how mutant gammaPKC affects the morphology and survival of cerebellar Purkinje cells (PCs), which are degenerated in SCA14 patients (PMID:19041943)
• ezrin is regulated during osteosarcoma metastasis by PKC (PMID:19060919)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Protein kinase C gamma, a causative for spinocerebellar ataxia, negatively regulates nuclear import of aprataxin. (PMID:19561170)
• PMA-responsive cPKC isoforms (alpha, beta and gamma) play a key role in negative regulation of CD98 signalling and homotypic aggregation (PMID:19895572)
• The presence of unphosphorylated PKC-gamma in HT29 cells, and its complete absence in Caco2 cells demonstrates a cell type-dependent differential coupling of Thr514-phosphorylation with de novo synthesis of PKC-gamma in colon cancer cells. (PMID:20188713)
• data support the idea that RanBP9 and RanBP10 may function as signaling integrators and dictate the efficient regulation of D(1) receptor signaling by PKCdelta and PKCgamma (PMID:20395553)
• These results indicate that autophagy contributes to the degradation of mutant gammaPKC, suggesting that autophagic inducers could provide therapeutic potential for SCA14. (PMID:20398063)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Protein Kinase C gamma rs3745406 polymorphism is not significantly associated with major depressive disorder. (PMID:20627017)
• Data show that through HINT1, the MOR facilitates the cross-talk of two NO- and zinc-regulated signal-transduction pathways, PKC/Src and Raf-1/ERK1/2, implicated in the negative control of morphine effects. (PMID:21235400)
• SCA14, a novel mutation in the PRKCG gene, was found in two families in Norway with autosomal dominant cerebellar ataxia. (PMID:21434874)
• cPLA(2)-dependent AA release is required for VEGF-induced Src-PLD1-PKCgamma-mediated pathological retinal angiogenesis (PMID:21536681)
• The Spinocerebellar ataxia type 14 is caused by mutations in the protein kinase C gamma (PKCgamma, PRKCG) gene with a hotspot for mutations in exon 4. Genetic testing for SCA14 is clinically available. (PMID:21827914)
• We propose that variety of mutant gammaPKC characters integrally and complicatedly participate in the pathophysiology of SCA 14. (PMID:21906004)
• Exome sequencing of large, 5-generational British kindred finds a novel p.Arg26Gly mutation in the PRKCG gene causing familial spinocerebellar ataxia 14. (PMID:22675081)
• Spinocerebellar ataxia type 14 mutant PKC-gamma upregulates Hsp70. Hsp70 has a role in degrading mutant PKC-gamma. (PMID:24021284)
• PKCgamma plays a critical role in cancer cells, and simultaneous inhibition of PKCgamma and Hsp90alpha synergistically prevents cell migration and promotes apoptosis in cancer cells. (PMID:24117238)
• we show that the mutation V138E of the protein kinase C gamma (PKCgamma) C1B domain, which is implicated in spinocerebellar ataxia type 14, exhibits a partially unfolded C-terminus (PMID:24134140)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcg	ENSDARG00000004561
mus_musculus	Prkcg	ENSMUSG00000078816
rattus_norvegicus	Prkcg	ENSRNOG00000054371
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Protein kinase C gamma type — P05129 (reviewed: P05129)

All UniProt accessions (6): P05129, A0A804HHY0, A0A804HIU5, H7BZ60, M0R0I9, M0R0Z4

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.

Subunit / interactions. Interacts with GRIA4. Interacts with CDCP1. Interacts with TP53INP1 and p53/TP53. Interacts with BMAL1.

Subcellular location. Cytoplasm. Perinuclear region. Cell membrane. Synapse. Synaptosome. Cell projection. Dendrite.

Tissue specificity. Expressed in Purkinje cells of the cerebellar cortex.

Post-translational modifications. Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4. Ubiquitinated.

Disease relevance. Spinocerebellar ataxia 14 (SCA14) [MIM:605361] Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA14 is an autosomal dominant cerebellar ataxia (ADCA). The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-514 (activation loop of the kinase domain), Thr-655 (turn motif) and Thr-674 (hydrophobic region), need to be phosphorylated for its full activation.

Cofactor. Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P05129-1	1	yes
P05129-2	2

RefSeq proteins (2): NP_001303258, NP_002730* (*=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
IPR014375	Protein_kinase_C_a/b/g	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00168, PF00433

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (66 total): binding site 16, modified residue 14, sequence variant 9, strand 9, helix 4, domain 3, splice variant 3, turn 3, zinc finger region 2, chain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2UZP	X-RAY DIFFRACTION	2
2E73	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05129-F1	82.32	0.53

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): 480 (proton acceptor)

Ligand- & substrate-binding residues (16): 193; 246; 246; 247; 248; 248; 248; 251; 252; 254; 254; 357–365 …

Post-translational modifications (14): 250, 320, 322, 326, 328, 330, 332, 373, 514, 648, 655, 674, 675, 687

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-111933	Calmodulin induced events
R-HSA-114516	Disinhibition of SNARE formation
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors
R-HSA-418597	G alpha (z) signalling events
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
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-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-372790	Signaling by GPCR
R-HSA-3858494	Beta-catenin independent WNT signaling
R-HSA-388396	GPCR downstream signalling
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity
R-HSA-4086400	PCP/CE pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 388 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_COGNITION, GOBP_BEHAVIOR, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, KEGG_MAPK_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, SP3_Q3, GOBP_RESPONSE_TO_ANGIOTENSIN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_RESPONSE_TO_FOOD

GO Biological Process (25): phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), chemical synaptic transmission (GO:0007268), learning or memory (GO:0007611), chemosensory behavior (GO:0007635), response to toxic substance (GO:0009636), negative regulation of protein ubiquitination (GO:0031397), regulation of response to food (GO:0032095), positive regulation of mismatch repair (GO:0032425), intracellular signal transduction (GO:0035556), negative regulation of protein catabolic process (GO:0042177), regulation of circadian rhythm (GO:0042752), response to morphine (GO:0043278), negative regulation of neuron apoptotic process (GO:0043524), response to pain (GO:0048265), rhythmic process (GO:0048511), regulation of phagocytosis (GO:0050764), long-term synaptic potentiation (GO:0060291), innervation (GO:0060384), presynaptic modulation of chemical synaptic transmission (GO:0099171), synaptic signaling via neuropeptide (GO:0099538), negative regulation of proteasomal protein catabolic process (GO:1901799), response to angiotensin (GO:1990776), response to psychosocial stress (GO:1990911), regulation of synaptic vesicle exocytosis (GO:2000300), protein phosphorylation (GO:0006468)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), calcium,diacylglycerol-dependent serine/threonine kinase activity (GO:0004698), protein serine/threonine/tyrosine kinase activity (GO:0004712), ATP binding (GO:0005524), zinc ion binding (GO:0008270), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (16): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), postsynaptic density (GO:0014069), dendrite (GO:0030425), calyx of Held (GO:0044305), perinuclear region of cytoplasm (GO:0048471), synaptic membrane (GO:0097060), presynaptic cytosol (GO:0099523), postsynaptic cytosol (GO:0099524), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Signal Transduction	2
CaM pathway	1
Response to elevated platelet cytosolic Ca2+	1
Trafficking of AMPA receptors	1
GPCR downstream signalling	1
PCP/CE pathway	1
Platelet activation, signaling and aggregation	1
G alpha (i) signalling events	1
PLC beta mediated events	1
Ca-dependent events	1
DAG and IP3 signaling	1
Opioid Signalling	1
G-protein mediated events	1
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein kinase activity	3
behavior	2
response to chemical	2
intracellular anatomical structure	2
presynapse	2
cytoplasm	2
cytosol	2
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
anterograde trans-synaptic signaling	1
cognition	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
response to food	1
regulation of response to nutrient levels	1
mismatch repair	1
regulation of mismatch repair	1
positive regulation of DNA repair	1
signal transduction	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
circadian rhythm	1
regulation of biological process	1
response to isoquinoline alkaloid	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
multicellular organismal response to stress	1
biological_process	1
phagocytosis	1
regulation of endocytosis	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
nerve development	1
multicellular organismal process	1
modulation of chemical synaptic transmission	1

Protein interactions and networks

STRING

2090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCG	CACNG7	P62955	802
PRKCG	CACNA1A	P78510	794
PRKCG	ATXN7	O15265	780
PRKCG	CACNG8	Q8WXS5	771
PRKCG	PLRG1	O43660	765
PRKCG	PPP2R2B	Q00005	726
PRKCG	SLC17A8	Q8NDX2	678
PRKCG	ATXN2	Q99700	668
PRKCG	SPTBN2	O15020	662
PRKCG	TRPC3	Q13507	658
PRKCG	ATXN1	P54253	648
PRKCG	KCNC3	Q14003	644
PRKCG	CALB1	P05937	640
PRKCG	ATXN3	P54252	626
PRKCG	CKM	P06732	625

IntAct

41 interactions, top by confidence:

A	B	Type	Score
PRKCG	PRKCA	psi-mi:“MI:0914”(association)	0.800
PRKCG	PRKCA	psi-mi:“MI:0915”(physical association)	0.800
KRT19	PRKCG	psi-mi:“MI:0915”(physical association)	0.560
PRKCG	PIAS1	psi-mi:“MI:0915”(physical association)	0.560
FAM167A	PRKCG	psi-mi:“MI:0915”(physical association)	0.560
TCP10L	PRKCG	psi-mi:“MI:0915”(physical association)	0.560
SAMD3	PRKCG	psi-mi:“MI:0915”(physical association)	0.560
PRKCG	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	DUSP11	psi-mi:“MI:0914”(association)	0.530
Trpc3	PRKCG	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	PRKCG	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PRKCG	Glrb	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
YWHAE	PRKCG	psi-mi:“MI:0915”(physical association)	0.400
SFN	PRKCG	psi-mi:“MI:0915”(physical association)	0.400
PTPN1	PRKCG	psi-mi:“MI:0915”(physical association)	0.370
	SGK1	psi-mi:“MI:0914”(association)	0.350
PRKCG	PRPSAP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (81): DAB2 (Biochemical Activity), CTNNB1 (Biochemical Activity), PRKCG (Biochemical Activity), UBE2T (Biochemical Activity), PRKCG (Affinity Capture-MS), PRKCG (Biochemical Activity), DNAJC5 (Biochemical Activity), ARHGEF7 (Biochemical Activity), MAPT (Biochemical Activity), PRKCG (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), SLC25A3 (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), PRPS1 (Affinity Capture-MS)

ESM2 similar proteins: A8KBH6, B6CZ17, B6CZ18, O75582, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P10102, P10829, P10830, P13677, P13678, P16054, P17252, P20444, P23298, P24723, P28867, P34722, P34885, P54644, P63318, P63319, P68403, P68404, P90980, Q02111, Q02156, Q05655, Q16974, Q16975, Q17941, Q1XHL7

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

58 interactions.

A	Effect	B	Mechanism
PRKCG	down-regulates	GSK3A	phosphorylation
PDPK1	up-regulates	PRKCG	phosphorylation
PRKCG	up-regulates	CHAT	phosphorylation
PRKCG	down-regulates	TNNI3	phosphorylation
PRKCG	down-regulates	KIR3DL1	phosphorylation
PRKCG	up-regulates	APTX	phosphorylation
“bisindolylmaleimide i”	down-regulates	PRKCG	“chemical inhibition”
3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione	down-regulates	PRKCG	“chemical inhibition”
PRKCG	up-regulates	ANXA1	phosphorylation
PRKCG	down-regulates	HSP90AA1	phosphorylation
PRKCG	up-regulates	ARHGEF7	phosphorylation
PRKCG	“down-regulates activity”	CYTH2	phosphorylation
PRKCG	“up-regulates activity”	GRK2	phosphorylation
PRKCG	unknown	CD5	phosphorylation
PRKCG	unknown	PA2G4	phosphorylation
PRKCG	“up-regulates activity”	TOP2A	phosphorylation
PRKCG	“up-regulates activity”	PSEN1	phosphorylation
PRKCG	“down-regulates activity”	HABP4	phosphorylation
PRKCG	“down-regulates activity”	NOS3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	5	17.9×	1e-03
intracellular signal transduction	5	10.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	30
Uncertain significance	193
Likely benign	43
Benign	54

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027481	NM_002739.5(PRKCG):c.1308C>G (p.Tyr436Ter)	Pathogenic
1298291	NM_002739.5(PRKCG):c.107A>G (p.His36Arg)	Pathogenic
13245	NM_002739.5(PRKCG):c.355T>C (p.Ser119Pro)	Pathogenic
13246	NM_002739.5(PRKCG):c.383G>A (p.Gly128Asp)	Pathogenic
13247	NM_002739.5(PRKCG):c.353G>A (p.Gly118Asp)	Pathogenic
13248	NM_002739.5(PRKCG):c.380A>G (p.Gln127Arg)	Pathogenic
13249	NM_002739.5(PRKCG):c.1927T>C (p.Phe643Leu)	Pathogenic
13251	NM_002739.5(PRKCG):c.303C>G (p.His101Gln)	Pathogenic
13252	NM_002739.5(PRKCG):c.2091_*98del (p.Met697_Ter698delinsXaa)	Pathogenic
29857	NM_002739.5(PRKCG):c.530_919del	Pathogenic
29858	NM_002739.5(PRKCG):c.1438G>T (p.Asp480Tyr)	Pathogenic
42129	NM_002739.5(PRKCG):c.1078G>A (p.Gly360Ser)	Pathogenic
42148	NM_002739.5(PRKCG):c.229T>A (p.Cys77Ser)	Pathogenic
42157	NM_002739.5(PRKCG):c.300_305del (p.His101_Lys102del)	Pathogenic
42161	NM_002739.5(PRKCG):c.341G>A (p.Cys114Tyr)	Pathogenic
42163	NM_002739.5(PRKCG):c.356C>T (p.Ser119Phe)	Pathogenic
42164	NM_002739.5(PRKCG):c.367G>A (p.Gly123Arg)	Pathogenic
42169	NM_002739.5(PRKCG):c.413T>A (p.Val138Glu)	Pathogenic
42170	NM_002739.5(PRKCG):c.449_450delinsTT (p.Cys150Phe)	Pathogenic
42171	NM_002739.5(PRKCG):c.417C>A (p.His139Gln)	Pathogenic
1027477	NM_002739.5(PRKCG):c.358C>T (p.Leu120Phe)	Likely pathogenic
1027478	NM_002739.5(PRKCG):c.1928T>G (p.Phe643Cys)	Likely pathogenic
1027479	NM_002739.5(PRKCG):c.1381G>A (p.Ala461Thr)	Likely pathogenic
1027509	NM_002739.5(PRKCG):c.380A>C (p.Gln127Pro)	Likely pathogenic
1184519	NM_002739.5(PRKCG):c.323A>G (p.Tyr108Cys)	Likely pathogenic
1184520	NM_002739.5(PRKCG):c.381G>T (p.Gln127His)	Likely pathogenic
1184521	NM_002739.5(PRKCG):c.394T>C (p.Ser132Pro)	Likely pathogenic
1283911	NM_002739.5(PRKCG):c.1926C>G (p.Asn642Lys)	Likely pathogenic
13250	NM_002739.5(PRKCG):c.1081A>G (p.Ser361Gly)	Likely pathogenic
1333855	NM_002739.5(PRKCG):c.220C>T (p.His74Tyr)	Likely pathogenic

SpliceAI

2304 predictions. Top by Δscore:

Variant	Effect	Δscore
19:53889634:CCAG:C	acceptor_loss	1.0000
19:53889635:CAGG:C	acceptor_loss	1.0000
19:53889636:A:AG	acceptor_gain	1.0000
19:53889636:AG:A	acceptor_gain	1.0000
19:53889636:AGG:A	acceptor_loss	1.0000
19:53889637:G:GG	acceptor_gain	1.0000
19:53889637:GG:G	acceptor_gain	1.0000
19:53889750:G:GG	donor_gain	1.0000
19:53889880:CTCCA:C	acceptor_loss	1.0000
19:53889881:TCCAG:T	acceptor_loss	1.0000
19:53889882:CCAG:C	acceptor_loss	1.0000
19:53889884:A:AG	acceptor_gain	1.0000
19:53889885:G:GC	acceptor_loss	1.0000
19:53889885:G:GG	acceptor_gain	1.0000
19:53889885:GGC:G	acceptor_gain	1.0000
19:53889885:GGCT:G	acceptor_gain	1.0000
19:53890000:A:G	donor_gain	1.0000
19:53890015:CTGG:C	donor_loss	1.0000
19:53890017:GGT:G	donor_loss	1.0000
19:53890019:T:A	donor_loss	1.0000
19:53891672:A:AG	acceptor_gain	1.0000
19:53891672:AGTT:A	acceptor_gain	1.0000
19:53891673:G:GG	acceptor_gain	1.0000
19:53891673:GTTG:G	acceptor_gain	1.0000
19:53891826:GTGTT:G	donor_gain	1.0000
19:53891828:GTT:G	donor_gain	1.0000
19:53891831:G:GG	donor_gain	1.0000
19:53892507:A:AG	acceptor_gain	1.0000
19:53892508:G:GG	acceptor_gain	1.0000
19:53892639:GGCTG:G	donor_gain	1.0000

AlphaMissense

4597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:53882600:C:A	H36N	1.000
19:53882600:C:G	H36D	1.000
19:53882602:C:A	H36Q	1.000
19:53882602:C:G	H36Q	1.000
19:53882606:T:C	F38L	1.000
19:53882607:T:C	F38S	1.000
19:53882607:T:G	F38C	1.000
19:53882608:C:A	F38L	1.000
19:53882608:C:G	F38L	1.000
19:53882636:T:C	F48L	1.000
19:53882638:C:A	F48L	1.000
19:53882638:C:G	F48L	1.000
19:53882639:T:A	C49S	1.000
19:53882639:T:C	C49R	1.000
19:53882639:T:G	C49G	1.000
19:53882640:G:A	C49Y	1.000
19:53882640:G:C	C49S	1.000
19:53882640:G:T	C49F	1.000
19:53882641:C:G	C49W	1.000
19:53882645:C:G	H51D	1.000
19:53882648:T:A	C52S	1.000
19:53882648:T:C	C52R	1.000
19:53882649:G:A	C52Y	1.000
19:53882649:G:C	C52S	1.000
19:53882649:G:T	C52F	1.000
19:53882650:C:G	C52W	1.000
19:53882657:T:C	F55L	1.000
19:53882658:T:C	F55S	1.000
19:53882659:C:A	F55L	1.000
19:53882659:C:G	F55L	1.000

dbSNP variants (sampled 300 via entrez): RS1000226683 (19:53891459 G>T), RS1000394991 (19:53883315 C>G,T), RS1000731235 (19:53881627 G>C), RS1000836491 (19:53891228 G>A), RS1000840589 (19:53888058 A>G), RS1000943057 (19:53894079 T>A,G), RS1001001732 (19:53893937 A>G), RS1001076812 (19:53885837 T>C), RS1001128696 (19:53891049 C>A,T), RS1001200260 (19:53907534 A>C), RS1001267258 (19:53901902 T>C), RS1001292655 (19:53887948 G>C), RS1001328989 (19:53882112 CGT>C), RS1001502601 (19:53893959 G>A), RS1001559709 (19:53900990 A>G)

Disease associations

OMIM: gene MIM:176980 | disease phenotypes: MIM:605361, MIM:615386, MIM:164400

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 14	Definitive	Autosomal dominant

Mondo (5): spinocerebellar ataxia type 14 (MONDO:0011540), cerebellar ataxia (MONDO:0000437), hereditary ataxia (MONDO:0100309), autosomal recessive spinocerebellar ataxia 14 (MONDO:0014159), autosomal dominant cerebellar ataxia (MONDO:0020380)

Orphanet (5): Spinocerebellar ataxia type 14 (Orphanet:98763), Rare ataxia (Orphanet:102002), Hereditary ataxia (Orphanet:183518), Spectrin-associated autosomal recessive cerebellar ataxia (Orphanet:352403), Autosomal dominant cerebellar ataxia (Orphanet:99)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000317	Facial myokymia
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000716	Depression
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001310	Dysmetria
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002073	Progressive cerebellar ataxia
HP:0002354	Memory impairment
HP:0002600	Hyporeflexia of lower limbs
HP:0003474	Somatic sensory dysfunction
HP:0003677	Slowly progressive
HP:0003829	Typified by incomplete penetrance
HP:0004373	Focal dystonia
HP:0005109	Abnormal Achilles tendon morphology
HP:0006855	Cerebellar vermis atrophy
HP:0006938	Impaired vibration sensation at ankles
HP:0007018	Attention deficit hyperactivity disorder
HP:0100543	Cognitive impairment

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
C531684	Hereditary spinal ataxia (supp.)
C537196	Spinocerebellar ataxia 14 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL2938 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 283,356 (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
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	516
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2	10,540
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL574737	UCN-01	2	2,217
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL362558	LY-2090314	2	108
CHEMBL3982723	DAROVASERTIB	2	473
CHEMBL475251	R-406	2	762
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL1084546	PF-00562271	1
CHEMBL1980391	RG-1530	1
CHEMBL3128043	PF-03758309	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Alpha subfamily

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.79	pKi
10-Me-Aplog-1	Activation	8.26	pKi
Gö 6983	Inhibition	8.22	pIC50
balanol	Inhibition	8.0	pIC50
GF109203X	Inhibition	7.7	pIC50
7-hydroxystaurosporine	Inhibition	7.52	pIC50
Ro-32-0432	Inhibition	7.44	pIC50
ruboxistaurin	Inhibition	6.52	pIC50
enzastaurin	Inhibition	5.7	pIC50

Binding affinities (BindingDB)

51 measured of 76 human assays (77 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
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL4435580	IC50	0.22 nM
CHEMBL4587471	IC50	0.36 nM
CHEMBL4575056	EC50	0.6 nM
2-{[2,6-dihydroxy-4-({[(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	22 nM
2-{[2,6-dihydroxy-4-({[(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	30 nM
6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]pyridin-3-yl}isoquinolin-3-amine	IC50	31 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
2-({2,6-dihydroxy-4-[({3-[(4-hydroxybenzene)amido]bicyclo[2.2.1]heptan-2-yl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	55 nM
2-({2,6-dihydroxy-4-[({3-[(4-hydroxybenzene)amido]azepan-4-yl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	67 nM
2-{[2,6-dihydroxy-4-({[(8R,9R)-9-[(4-hydroxybenzene)amido]tricyclo[5.2.1.0^{2,6}]decan-8-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	100 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-2-[(phenylsulfonyl)amino]propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	110 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	160 nM
2-[(4-{[(2S)-2-benzenesulfonamido-3-(4-hydroxyphenyl)propoxy]carbonyl}-2,6-dihydroxyphenyl)carbonyl]-3-hydroxybenzoic acid	IC50	210 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-(4-hydroxyphenoxy)cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	220 nM
6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-2-ethynylpyridin-3-yl}isoquinoline	IC50	260 nM
(+-)-anti-3-[[4-(6-Carboxy-2-hydroxybenzoyl)-3,5-hydroxybenzoyl]oxy]-4-(4-hydroxybenzyl)pyrrolidine, Trifluoroacetic Acid Salt	IC50	260 nM
13a (S-)	IC50	270 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cycloheptyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	270 nM
2-({2,6-dihydroxy-4-[({3-[(4-hydroxybenzene)amido]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	410 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-1-methylpropyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	410 nM
2-{[2,6-dihydroxy-4-({[(4S)-3-[(4-hydroxybenzene)amido]-1-azabicyclo[3.2.2]nonan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	415 nM
6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-2-chloropyridin-3-yl}isoquinoline	IC50	540 nM
3-[(2S)-2-amino-3-({5-[(E)-2-(pyridin-4-yl)ethenyl]pyridin-3-yl}oxy)propyl]-1H-indole	IC50	1200 nM
(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate	IC50	1400 nM
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
2-[(4-{[(2R)-2-benzenesulfonamido-3-(4-hydroxyphenyl)propoxy]carbonyl}-2,6-dihydroxyphenyl)carbonyl]-3-hydroxybenzoic acid	IC50	1900 nM
2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	1900 nM
(3S,4R)-4-[(4-hydroxyphenyl)methyl]pyrrolidin-3-yl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate	IC50	2200 nM
2-{[2,6-dihydroxy-4-({[(8S,9R)-9-[(4-hydroxybenzene)amido]tricyclo[5.2.1.0^{2,6}]decan-8-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	2700 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-2-[(naphthylsulfonyl)amino]propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	3200 nM
2-[(2,6-dihydroxy-4-{[4-(4-hydroxyphenyl)butoxy]carbonyl}phenyl)carbonyl]-3-hydroxybenzoic acid	IC50	3300 nM
2-[(4-{[2-(dimethylamino)-3-(4-hydroxyphenyl)propoxy]carbonyl}-2,6-dihydroxyphenyl)carbonyl]-3-hydroxybenzoic acid	IC50	4000 nM
2-{[2,6-dihydroxy-4-({[(3R,4R)-3-[(4-hydroxybenzene)amido]piperidin-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	5100 nM
2-{[2,6-dihydroxy-4-({[(3R,4R)-3-[(4-hydroxybenzene)amido]-1-[(4-methylbenzene)sulfonyl]azepan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	6100 nM
3-(4-hydroxyphenyl)propyl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate	IC50	7800 nM
2-[[2,6-Dihydroxy-4-[[2-[[(4-hydroxyphenyl)carbonyl]amino]ethoxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	11000 nM
2-{[2,6-dihydroxy-4-({[(4S)-3-[(4-hydroxybenzene)amido]-1-azabicyclo[3.2.2]nonan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	12000 nM
CHEMBL411351	IC50	15000 nM
CHEMBL3215313	IC50	17000 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-2-[[(4-hydroxyphenyl)carbonyl]amino]propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	18000 nM
2-[(4-{[2-benzenesulfonamido-3-(4-hydroxyphenoxy)propoxy]carbonyl}-2,6-dihydroxyphenyl)carbonyl]-3-hydroxybenzoic acid	IC50	18000 nM
(S)-Methyl 2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-2-[(phenylsulfonyl)amino]propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoate	IC50	18000 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-2-[(methylsulfonyl)amino]propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	23000 nM
CHEMBL81478	IC50	30000 nM

ChEMBL bioactivities

689 potent at pChembl≥5 of 787 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
9.80	Kd	0.16	nM	CHEMBL337834
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
9.42	Ki	0.38	nM	DEBROMOAPLYSIATOXIN
9.27	IC50	0.542	nM	STAUROSPORINE
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.20	Ki	0.63	nM	APLYSIATOXIN
9.19	Ki	0.65	nM	CHEMBL5175742
9.16	Ki	0.69	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1.01	nM	STAUROSPORINE
8.92	Kd	1.19	nM	CHEMBL27768
8.92	Ki	1.2	nM	CHEMBL285801
8.85	IC50	1.43	nM	STAUROSPORINE
8.82	Kd	1.5	nM	CHEMBL27768
8.82	Ki	1.5	nM	CHEMBL337834
8.80	Ki	1.58	nM	CHEMBL27768
8.77	IC50	1.7	nM	CHEMBL291126
8.73	Ki	1.84	nM	CHEMBL265998
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	IC50	2	nM	GO-6976
8.66	IC50	2.2	nM	CHEMBL83790
8.57	IC50	2.7	nM	STAUROSPORINE
8.56	IC50	2.76	nM	STAUROSPORINE
8.54	Ki	2.91	nM	CHEMBL27768
8.52	IC50	3	nM	STAUROSPORINE
8.50	Ki	3.162	nM	CHEMBL1980995
8.39	IC50	4.1	nM	UCN-01
8.31	Ki	4.9	nM	PHORBOL MYRISTATE ACETATE
8.30	IC50	5	nM	CHEMBL306427
8.30	IC50	5	nM	CHEMBL417051
8.30	IC50	5	nM	CHEMBL421866
8.30	IC50	5	nM	CHEMBL538718
8.30	IC50	5	nM	CHEMBL432168
8.30	IC50	5	nM	CHEMBL307708
8.30	IC50	5	nM	CHEMBL75661
8.30	IC50	5	nM	CHEMBL300422
8.28	Ki	5.3	nM	BALANOL
8.28	Ki	5.23	nM	CHEMBL265998

PubChem BioAssay actives

376 with measured affinity, of 1901 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
[(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
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	164011: Binding affinity for human Protein kinase C gamma with [Ca2+]	kd	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
(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	687831: Inhibition of [3H]PDBu binding to PKCgamma C1A domain	ki	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	517264: Inhibition of [3H]PDBu binding to PKC gamma C1A peptide	ki	0.0006	uM
[(1R,2S,6R,10S,11R,13S,15R)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-naphthalen-1-ylacetate	1845945: Displacement of 3H-PDBu from recombinant human PKCgamma incubated for 25 mins by scintillation counter analysis	ki	0.0006	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	768064: Displacement of [3H]PDBu from PKCgamma C1A domain (unknown origin)	ki	0.0007	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	164025: Displacement of [3H]- PDBu from recombinant PKC gamma expressed in baculovirus	ki	0.0012	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	164034: Binding affinity for Protein kinase C gamma C1b domain	kd	0.0012	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
[(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	164039: Displacement of 3[H]PDBu from Protein kinase C gamma C1b domain	ki	0.0018	uM
3-(23-methyl-14-oxo-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-3-yl)propanenitrile	325570: Inhibition of PKCgamma	ic50	0.0020	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	221771: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C gamma	ki	0.0049	uM
2-[4-[(1R,2R,4S)-4-(aminomethyl)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0050	uM
2-[2,6-dihydroxy-4-[(1R,2R,4S)-2-[(4-hydroxybenzoyl)amino]-4-(hydroxymethyl)cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0050	uM
2-[4-[(1R,2R,4R)-4-amino-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0050	uM
2-[2,6-dihydroxy-4-[4-[(4-hydroxyphenyl)methyl]pyrrolidin-3-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163879: Evaluated against recombinant human Protein kinase C gamma	ic50	0.0050	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	254306: Inhibitory constant against protein kinase C	ki	0.0053	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	687831: Inhibition of [3H]PDBu binding to PKCgamma C1A domain	ki	0.0055	uM
[2-(hydroxymethyl)-5-oxo-4-propan-2-ylideneoxolan-2-yl]methyl 4-[2-(4-methylphenyl)ethynyl]benzoate	350006: Displacement of [3H]PDBu form human PKCgamma in presence of phosphatidylserine	ki	0.0062	uM
2-[4-[(1R,2R,4R)-4-(aminomethyl)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0100	uM
2-[2,6-dihydroxy-4-[(1R,2R)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0100	uM
2-[2,6-dihydroxy-4-[2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163879: Evaluated against recombinant human Protein kinase C gamma	ic50	0.0100	uM
(1S,3R,5R,9R,13S,14R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-14,16,16-trimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687831: Inhibition of [3H]PDBu binding to PKCgamma C1A domain	ki	0.0120	uM
[2-(hydroxymethyl)-5-oxo-4-propan-2-ylideneoxolan-2-yl]methyl 4-[4-[2-(4-methylphenyl)ethynyl]phenoxy]butanoate	350006: Displacement of [3H]PDBu form human PKCgamma in presence of phosphatidylserine	ki	0.0123	uM
2-[2,6-dihydroxy-4-[(3R,4R)-4-[(4-hydroxybenzoyl)amino]pyrrolidin-3-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0130	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	312185: Displacement of [3H]PDBu from PKCgamma C1A domain	ki	0.0150	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-(2-hydroxyethyl)piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0160	uM
(10S,13S)-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	164025: Displacement of [3H]- PDBu from recombinant PKC gamma expressed in baculovirus	ki	0.0194	uM
2-[2,6-dihydroxy-4-[(1R,2R)-4-hydroxy-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0200	uM
[(1R,2S,6R,10S,11R,13S,15R)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] acetate	1845945: Displacement of 3H-PDBu from recombinant human PKCgamma incubated for 25 mins by scintillation counter analysis	ki	0.0218	uM
(2S,5S)-9-decyl-5-(hydroxymethyl)-1-methyl-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	2163933: Activation of PKC in human ACH-2 cells infected with latent HIV-1 assessed as reversal of HIV-1 latency by measuring increase in p24 antigen level incubated for 48 hrs by chemiluminescent enzyme immunoassay	ec50	0.0250	uM
2-[2,6-dihydroxy-4-[(1R,2R,4R)-4-hydroxy-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0300	uM
2-[2,6-dihydroxy-4-[3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163879: Evaluated against recombinant human Protein kinase C gamma	ic50	0.0300	uM
3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	385590: Inhibition of human PKCgamma	ic50	0.0300	uM
6-[5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-3-pyridinyl]isoquinolin-3-amine	1797573: PKA/PKC Kinase Assay from Article 10.1016/j.bmcl.2006.03.041: “Isoquinoline-pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity.”	ic50	0.0310	uM
4-[[[6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]amino]methyl]phenol	1180278: Inhibition of PKC (unknown origin) using C1 peptide substrate	ic50	0.0350	uM
[2-(hydroxymethyl)-5-oxo-4-propan-2-ylideneoxolan-2-yl]methyl 3-[4-[2-(4-methylphenyl)ethynyl]phenoxy]propanoate	350006: Displacement of [3H]PDBu form human PKCgamma in presence of phosphatidylserine	ki	0.0350	uM
(1S,3R,5R,9R,13R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-16,16-dimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	517264: Inhibition of [3H]PDBu binding to PKC gamma C1A peptide	ki	0.0390	uM
2-[2,6-dihydroxy-4-[2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163879: Evaluated against recombinant human Protein kinase C gamma	ic50	0.0400	uM
2-[2,6-dihydroxy-4-[[(2R,3R)-3-[(4-hydroxybenzoyl)amino]-2-bicyclo[2.2.1]heptanyl]oxycarbonyl]benzoyl]-3-hydroxybenzoic acid	164004: Inhibitory concentration against recombinant human Protein kinase C gamma isozyme	ic50	0.0400	uM
2-[2,6-dihydroxy-4-[(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1795485: PKC assay from Article 10.1021/jm960581w: “Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A.”	ic50	0.0400	uM
2-[2,6-dihydroxy-4-[(3S,4R)-4-[(4-hydroxyphenyl)methyl]pyrrolidin-3-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1795485: PKC assay from Article 10.1021/jm960581w: “Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A.”	ic50	0.0400	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	affects localization, decreases reaction, decreases expression, increases activity	4
sodium arsenite	affects splicing, decreases expression	2
Diethylhexyl Phthalate	decreases expression, affects reaction, decreases reaction, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
FR900359	decreases phosphorylation	1
naringenin	affects localization, decreases reaction	1
mezerein	affects cotreatment, decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
bryostatin 1	affects cotreatment, decreases expression	1
lipopolysaccharide, Escherichia coli O111 B4	affects reaction, decreases reaction, increases expression	1
abrine	increases expression	1
3-((5-(6-((3-chlorophenyl)amino)pyrazinyl)-3-pyridinyl)amino)-1-propanol	affects binding, decreases activity	1
bisphenol S	increases methylation	1
Pioglitazone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Butyrates	increases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Hydrogen Peroxide	affects expression	1
Lithium	affects binding, decreases reaction	1
Pesticides	decreases methylation	1
Smoke	increases expression	1
Thiram	decreases activity	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Sirolimus	affects binding, decreases reaction, increases degradation	1

ChEMBL screening assays

627 unique, capped per target: 611 binding, 15 functional, 1 admet

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
CHEMBL4424905	ADMET	Inhibition of human full-length N-terminal His6-tagged PKCgamma expressed in baculovirus infected Sf21 insect cells using Histone H1 as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

12 cell lines: 9 cancer cell line, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1Q5	Abcam K-562 PRKCG KO	Cancer cell line	Female
CVCL_D1U4	Abcam U-87MG PRKCG KO	Cancer cell line	Male
CVCL_D2LR	Abcam Raji PRKCG KO	Cancer cell line	Male
CVCL_D7YI	Ubigene A-549 PRKCG KO	Cancer cell line	Male
CVCL_D8TY	Ubigene HCT 116 PRKCG KO	Cancer cell line	Male
CVCL_E4VT	KOLF2.1J PRKCG 24.4kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_E7LZ	KOLF2.1J PRKCG F643L SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7M0	KOLF2.1J PRKCG F643L SNV/WT	Induced pluripotent stem cell	Male
CVCL_TG87	HAP1 PRKCG (-) 1	Cancer cell line	Male
CVCL_TG88	HAP1 PRKCG (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01104649	PHASE2/PHASE3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893	PHASE2/PHASE3	COMPLETED	Trial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361	PHASE1/PHASE2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687	PHASE1/PHASE2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	PHASE1/PHASE2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
NCT00001324	Not specified	COMPLETED	PET Scan to Study Brain Control of Human Movement
NCT00006492	Not specified	COMPLETED	Gluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00272272	Not specified	COMPLETED	Fall Prevention in a Geriatric Nursing Home Setting Using the Music of Nolwenn Leroy
NCT00654251	Not specified	COMPLETED	Measuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias
NCT00692861	Not specified	COMPLETED	Autoimmunity in Neurologic Complications of Celiac Disease
NCT01037777	Not specified	COMPLETED	RISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
NCT01307176	Not specified	COMPLETED	Exercise Training Program for Cerebellar Ataxia