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): 420 total — 20 pathogenic, 36 likely-pathogenic (top 8% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 7 regions constrained (≈19% of expected missense variation)
• GTEx eGene: eQTL in 4 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 30
• ChEMBL bioactivity: 23 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.48 (moderately constrained)
• MANE Select transcript: NM_002739
• Interaction hub: 1,925 STRING partners (top 8% of genes corpus-wide)

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: 11 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000263431

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

ENST00000263431, ENST00000419486, ENST00000474397, ENST00000479081, ENST00000682028, ENST00000682268, ENST00000682676, ENST00000682902, ENST00000683513, ENST00001059646, ENST00001141984

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.

Highest expression (Bgee): frontal lobe, nucleus accumbens, prefrontal cortex, amygdala, Brodmann (1909) area 9.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKCG is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	1.4e-25	-2.07	19:53882183:A:C
Pituitary	eqtl	7.7e-06	-1.25	19:53882183:A:C
Whole Blood	eqtl	2.9e-02	-0.55	19:53894210:C:T
Skin Sun Exposed Lower leg	eqtl	3.0e-02	-0.22	19:54424853:A:C

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

showing 100 of 264 tissues 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
parietal lobe	UBERON:0001872	73.61	gold quality
parotid gland	UBERON:0001831	72.54	gold quality
cortical plate	UBERON:0005343	72.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.69	gold quality
primary visual cortex	UBERON:0002436	70.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.18	gold quality
right testis	UBERON:0004534	68.83	gold quality
left testis	UBERON:0004533	68.20	gold quality
substantia nigra	UBERON:0002038	67.45	gold quality
occipital lobe	UBERON:0002021	67.28	gold quality
buccal mucosa cell	CL:0002336	67.19	gold quality
biceps brachii	UBERON:0001507	67.12	gold quality
triceps brachii	UBERON:0001509	66.54	gold quality
gluteal muscle	UBERON:0002000	66.39	gold quality
testis	UBERON:0000473	66.38	gold quality
midbrain	UBERON:0001891	66.38	gold quality
endothelial cell	CL:0000115	66.23	gold quality
cerebellar vermis	UBERON:0004720	66.04	silver quality
trabecular bone tissue	UBERON:0002483	65.81	gold quality
Brodmann (1909) area 10	UBERON:0013541	65.63	silver quality
germinal epithelium of ovary	UBERON:0001304	65.58	gold quality
left ventricle myocardium	UBERON:0006566	65.38	gold quality
lateral nuclear group of thalamus	UBERON:0002736	64.02	silver quality
cardiac muscle of right atrium	UBERON:0003379	63.80	gold quality
myocardium	UBERON:0002349	63.74	gold quality
upper arm skin	UBERON:0004263	63.63	gold quality
middle temporal gyrus	UBERON:0002771	63.62	silver quality
frontal pole	UBERON:0002795	63.56	gold quality
bone marrow	UBERON:0002371	63.11	gold quality
amniotic fluid	UBERON:0000173	63.02	gold quality
deltoid	UBERON:0001476	62.79	gold quality
quadriceps femoris	UBERON:0001377	62.64	gold quality
vastus lateralis	UBERON:0001379	62.64	gold quality
sperm	CL:0000019	62.62	gold quality
nasal cavity epithelium	UBERON:0005384	61.78	gold quality
male germ cell	CL:0000015	61.76	gold quality
palpebral conjunctiva	UBERON:0001812	61.72	gold quality
tendon of biceps brachii	UBERON:0008188	61.57	gold quality
cartilage tissue	UBERON:0002418	61.46	gold quality
pigmented layer of retina	UBERON:0001782	61.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	61.10	silver quality
gingiva	UBERON:0001828	60.68	gold quality
middle frontal gyrus	UBERON:0002702	60.62	gold quality
decidua	UBERON:0002450	60.45	gold quality
mammalian vulva	UBERON:0000997	60.34	gold quality
paraflocculus	UBERON:0005351	60.18	gold quality
vena cava	UBERON:0004087	59.79	gold quality
esophagus squamous epithelium	UBERON:0006920	59.74	gold quality
mucosa of sigmoid colon	UBERON:0004993	59.65	gold quality
ileal mucosa	UBERON:0000331	59.62	silver quality
dorsal plus ventral thalamus	UBERON:0001897	59.50	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	59.36	gold quality
lateral globus pallidus	UBERON:0002476	59.28	silver quality
thymus	UBERON:0002370	59.11	gold quality
spinal cord	UBERON:0002240	58.97	gold quality
epithelium of esophagus	UBERON:0001976	58.74	gold quality
gingival epithelium	UBERON:0001949	58.61	gold quality
seminal vesicle	UBERON:0000998	58.45	gold quality
bronchial epithelial cell	CL:0002328	58.28	gold quality
squamous epithelium	UBERON:0006914	58.23	gold quality
islet of Langerhans	UBERON:0000006	58.03	gold quality
heart right ventricle	UBERON:0002080	57.96	gold quality
epithelium of nasopharynx	UBERON:0001951	57.76	gold quality
corpus callosum	UBERON:0002336	57.63	gold quality
ventral tegmental area	UBERON:0002691	57.57	silver quality
mammary duct	UBERON:0001765	57.41	gold quality
adult organism	UBERON:0007023	57.28	silver quality
epithelium of mammary gland	UBERON:0003244	57.17	gold quality
epithelium of bronchus	UBERON:0002031	57.09	gold quality
oral cavity	UBERON:0000167	57.08	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

HPA expression

RNA tissue specificity: Tissue enriched

49 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampal formation	tissue	299.6
Hippocampus	tissue	193.1	high
Frontal cortex	tissue	177.4
Cerebral cortex	tissue	175.2	low
Motor cortex	tissue	175.2
Retrosplenial cortex	tissue	161.3
Prefrontal cortex	tissue	155.2
Retrosplenial and cingulate cortex	tissue	150.2
Temporal cortex	tissue	147.6
Entorhinal cortex	tissue	143.9
Insular cortex	tissue	141.2
Amygdala	tissue	128.3
Caudate putamen	tissue	124.8
Nucleus accumbens	tissue	124.7
Thalamus	tissue	119.5
Basal ganglia	tissue	114.7	not detected
Cerebellum	tissue	108.3	high
Postcentral gyrus	tissue	104.6
Somatosensory cortex	tissue	101.9
Occipital cortex	tissue	86.0
Superior colliculi	tissue	85.4
Midbrain	tissue	79.4
Ventral forebrain	tissue	79.4
Septum	tissue	66.3
Pons	tissue	65.2
Putamen	tissue	49.1
Periaqueductal gray	tissue	33.1
Hypothalamus	tissue	29.3
Olfactory bulb	tissue	26.9
Substantia nigra	tissue	15.2
Medulla oblongata	tissue	12.1
Corpus callosum	tissue	10.2
Locus coeruleus	tissue	9.4
Spinal cord	tissue	8.0
Parathyroid gland	tissue	1.8	not detected
Thymus	tissue	1.8
Choroid plexus	tissue	1.7
Pancreas	tissue	1.5	not detected
Testis	tissue	1.3	not detected
Bone marrow	tissue	0.7	not detected
Pituitary gland	tissue	0.3
Stomach 1	tissue	0.3	not detected
Tongue	tissue	0.2
Retina	tissue	0.1
Smooth muscle	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected
Duodenum	tissue	0.1	not detected
Fallopian tube	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Dorsal hippocampus (299.6), Ventral hippocampus (256.3), Hippocampus, CA1 (246.9), Hippocampus, CA3 (209.3), Subiculum (200.0).

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)

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

showing 30 of 81 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.994, LOEUF 0.476, missense Z 3.84 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000263431 splits into 7 regions with different missense tolerance; 2 are missense-constrained (≈19% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:53,882,495–53,882,547	27 / 23.9	1.13	no
19:53,882,548–53,889,741	50 / 146.5	0.34	yes (p 1.5e-15)
19:53,889,742–53,898,082	261 / 312.1	0.84	no
19:53,898,083–53,898,545	22 / 59.0	0.37	no
19:53,898,546–53,900,474	78 / 105.6	0.74	no
19:53,900,475–53,900,683	4 / 32.3	0.12	yes (p 6.3e-07)
19:53,900,684–53,906,892	198 / 273.4	0.72	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97597) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired behavioral response to alcohol	2
abnormal cerebellar molecular layer	1
decreased anxiety-related response	1
ataxia	1
impaired coordination	1
abnormal gait	1
abnormal spatial learning	1
abnormal contextual conditioning behavior	1
reduced long-term potentiation	1
decreased inflammatory response	1
abnormal pain threshold	1
alcohol preference	1
abnormal innervation	1
abnormal nociception after inflammation	1
abnormal excitatory postsynaptic currents	1
abnormal Purkinje cell dendrite morphology	1
enhanced behavioral response to alcohol	1
abnormal impulsive behavior control	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Bos taurus	P48018	99.8%	Diamond
Pongo abelii	Q5R4J5	99.8%	Diamond
Macaca fascicularis	Q60HC0	99.8%	Diamond
Oryctolagus cuniculus	P05772	99.4%	Diamond
Anser cygnoides	A0A075F932	98.8%	Diamond
Gallus gallus	P47191	98.8%	Diamond
Xenopus laevis	Q6IP76	97.1%	Diamond
Xenopus tropicalis	Q67E00	95.4%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
VSTM1	protein-coding	284415
CACNG8	protein-coding	59283
CACNG7	protein-coding	59284
CACNG6	protein-coding	59285
MIR373	ncRNA	442918
NLRP12	protein-coding	91662
MYADM	protein-coding	91663
MIR935	ncRNA	100126325
MYADM-AS1	ncRNA	105372457
MIR372	ncRNA	442917

Protein

Protein identifiers

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

All UniProt accessions (7): A0A804HHY0, A0A804HIU5, B7Z870, P05129, 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)

• 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): binding site 16, modified residue 14, sequence variant 9, strand 9, helix 7, 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 by resolution:

PDB	Title	Method	Resolution (Å)
2UZP	Crystal structure of the C2 domain of human protein kinase C gamma.	X-RAY DIFFRACTION	2
2E73	Solution structure of the phorbol esters/diacylglycerol binding domain of protein kinase …	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, AGC Ser/Thr protein kinases, Predicted intracellular proteins, RAS pathway related proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
480	proton acceptor

Ligand- & substrate-binding residues (16)

Position	Role
193	Ca(2+)
246	Ca(2+)
247	Ca(2+)
248	Ca(2+)
251	Ca(2+)
252	Ca(2+)
254	Ca(2+)
357–365	ATP
380	ATP
186	Ca(2+)
187	Ca(2+)

Post-translational modifications (14)

Type	Positions
Phosphothreonine	250, 332, 514, 648, 655, 674
Phosphoserine	320, 322, 326, 328, 330, 373, 687
Phosphotyrosine	675

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 27; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

27 pathways:

ID	Pathway	Evidence
R-HSA-111933	Calmodulin induced events	curated
R-HSA-114516	Disinhibition of SNARE formation	curated
R-HSA-76005	Response to elevated platelet cytosolic Ca2+	curated
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors	curated
R-HSA-5099900	WNT5A-dependent internalization of FZD4	curated
R-HSA-3858494	Beta-catenin independent WNT signaling	—
R-HSA-111996	Ca-dependent events	—
R-HSA-111997	CaM pathway	—
R-HSA-1489509	DAG and IP3 signaling	—
R-HSA-418594	G alpha (i) signalling events	—
R-HSA-418597	G alpha (z) signalling events	electronic
R-HSA-112040	G-protein mediated events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity	—
R-HSA-109582	Hemostasis	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-111885	Opioid Signalling	—
R-HSA-4086400	PCP/CE pathway	—
R-HSA-112043	PLC beta mediated events	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-195721	Signaling by WNT	—
R-HSA-399719	Trafficking of AMPA receptors	—
R-HSA-112315	Transmission across Chemical Synapses	—

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 (21): phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), chemical synaptic transmission (GO:0007268), learning or memory (GO:0007611), 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), long-term synaptic potentiation (GO:0060291), innervation (GO:0060384), 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 (14): 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), neuron projection (GO:0043005), synapse (GO:0045202)

Reactome top-level categories

17 top-level categories:

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
Intracellular signaling by second messengers	1
Signaling by WNT	1

GO top-level categories

showing 60 of 74 GO namespaces:

Category	Terms
protein kinase activity	3
cellular anatomical structure	3
intracellular anatomical structure	2
multicellular organismal response to stress	2
cytoplasm	2
cytosol	2
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
anterograde trans-synaptic signaling	1
behavior	1
cognition	1
response to chemical	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
biological_process	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
nerve development	1
multicellular organismal process	1
proteasomal protein catabolic process	1
negative regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
response to peptide hormone	1
synaptic vesicle exocytosis	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
diacylglycerol-dependent serine/threonine kinase activity	1
calcium-dependent protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transition metal ion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 48 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of protein catabolic process	BP	direct assay
negative regulation of protein ubiquitination	BP	direct assay
phospholipase C-activating G protein-coupled receptor signaling pathway	BP	direct assay
positive regulation of mismatch repair	BP	direct assay
calcium,diacylglycerol-dependent serine/threonine kinase activity	MF	direct assay
protein kinase activity	MF	direct assay
protein serine/threonine/tyrosine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,925 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCG	CACNG7	P62955	794
PRKCG	CACNA1A	P78510	780
PRKCG	CACNG8	Q8WXS5	778
PRKCG	ATXN7	O15265	773
PRKCG	PLRG1	O43660	758
PRKCG	PPP2R2B	Q00005	680
PRKCG	ATXN2	Q99700	655
PRKCG	SPTBN2	O15020	650
PRKCG	ATXN1	P54253	618
PRKCG	CALB1	P05937	617
PRKCG	ATXN3	P54252	609
PRKCG	GRIA4	P48058	608
PRKCG	KCNC3	Q14003	606
PRKCG	PRPF31	Q8WWY3	576
PRKCG	ATXN10	Q9UBB4	570

IntAct

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

17 partners by confidence:

Partner	Interaction type	MIscore	Records
PRKCA	association	0.800	2
FAM167A	physical association	0.560	3
KRT19	physical association	0.560	3
PIAS1	physical association	0.560	3
SAMD3	physical association	0.560	3
TCP10L	physical association	0.560	3
HSP90AB1	physical association	0.560	1
YWHAE	physical association	0.400	2
SFN	physical association	0.400	1
PTPN1	physical association	0.370	2
HSPB1	association	0.350	1
PRKCB	association	0.350	1
PRPSAP2	association	0.350	1
PICK1	physical association	0.000	2
CCHCR1	physical association	0.000	1
EXOC5	physical association	0.000	1
NOXA1	physical association	0.000	1

BioGRID (81 interactions; top human partners by supporting records): PRKCA (Affinity Capture-MS; 4 records), GRIA4 (Affinity Capture-Western; 2 records), HSP90AA1 (Affinity Capture-MS; 2 records), RANBP10 (Reconstituted Complex; 2 records), AFAP1 (Reconstituted Complex), AIFM1 (Affinity Capture-MS), APP (Reconstituted Complex), ARHGEF25 (Reconstituted Complex), ARHGEF7 (Biochemical Activity), BAG2 (Affinity Capture-MS), CASR (Biochemical Activity), CCHCR1 (Two-hybrid), CDC37 (Affinity Capture-MS), CTNNB1 (Biochemical Activity), DAB2 (Biochemical Activity)

SIGNOR signaling

showing 42 of 58 signaling 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
PRKCG	up-regulates	AMPA	phosphorylation
PRKCG	up-regulates	RAF1	phosphorylation
PRKCG	up-regulates	GRK2	phosphorylation
PRKCG	up-regulates	CD5	phosphorylation
PRKCG	unknown	RPS6KB2	phosphorylation
PRKCG	up-regulates	GRIA4	phosphorylation
PRKCG	unknown	EIF4E	phosphorylation
PRKCG	“down-regulates activity”	STK17B	phosphorylation
PRKCG	“down-regulates activity”	GJA1	phosphorylation
PRKCG	“up-regulates activity”	PEBP1	phosphorylation
PRKCG	“up-regulates activity”	GRIN1	phosphorylation
PRKCG	“up-regulates activity”	NRGN	phosphorylation
PRKCG	“up-regulates quantity by stabilization”	VTN	phosphorylation
PRKCG	unknown	SDC2	phosphorylation
PRKCG	unknown	DAB2	phosphorylation
PRKCG	“up-regulates activity”	GRIN2B	phosphorylation
PRKCG	“up-regulates activity”	OCLN	phosphorylation
PRKCG	unknown	STXBP1	phosphorylation
PRKCG	“down-regulates activity”	STXBP1	phosphorylation
PRKCG	“up-regulates activity”	GRM5	phosphorylation
PRKCG	“up-regulates activity”	MGluR	phosphorylation
PRKCG	“down-regulates activity”	MAPT	phosphorylation
PRKCG	“up-regulates activity”	GSTP1	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for PRKCG: 420 ClinVar records (56 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	36
Uncertain significance	205
Likely benign	57
Benign	50

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 56 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
13248	NM_002739.5(PRKCG):c.380A>G (p.Gln127Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
42169	NM_002739.5(PRKCG):c.413T>A (p.Val138Glu)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
42140	NM_002739.5(PRKCG):c.188G>T (p.Gly63Val)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	5
804150	NM_002739.5(PRKCG):c.379C>A (p.Gln127Lys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1027477	NM_002739.5(PRKCG):c.358C>T (p.Leu120Phe)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1283911	NM_002739.5(PRKCG):c.1926C>G (p.Asn642Lys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1333855	NM_002739.5(PRKCG):c.220C>T (p.His74Tyr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3584067	NM_002739.5(PRKCG):c.220C>A (p.His74Asn)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
13247	NM_002739.5(PRKCG):c.353G>A (p.Gly118Asp)	Pathogenic	criteria provided, single submitter	6
13245	NM_002739.5(PRKCG):c.355T>C (p.Ser119Pro)	Pathogenic	criteria provided, single submitter	3
13246	NM_002739.5(PRKCG):c.383G>A (p.Gly128Asp)	Pathogenic	criteria provided, single submitter	3
13249	NM_002739.5(PRKCG):c.1927T>C (p.Phe643Leu)	Pathogenic	criteria provided, single submitter	3
42163	NM_002739.5(PRKCG):c.356C>T (p.Ser119Phe)	Pathogenic	criteria provided, single submitter	2
1027481	NM_002739.5(PRKCG):c.1308C>G (p.Tyr436Ter)	Pathogenic	criteria provided, single submitter	1
13250	NM_002739.5(PRKCG):c.1081A>G (p.Ser361Gly)	Likely pathogenic	criteria provided, single submitter	3

Per-variant reference — Sugi Variant

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 1,155):

Position(s)	Effect	Δscore	Sites
19:53889636–53889637	acceptor_loss	1.0000	6
19:53889884–53889885	acceptor_loss	1.0000	4
19:53890000	donor_gain	1.0000
19:53890018–53890019	donor_loss	1.0000	5
19:53892644–53892645	donor_loss	1.0000	5
19:53898109	donor_gain	1.0000
19:53900231–53900232	acceptor_loss	1.0000	5
19:53900406	acceptor_gain	1.0000
19:53900409	acceptor_gain	1.0000
19:53900417–53900418	acceptor_loss	1.0000	6

AlphaMissense

2,890 missense substitutions predicted likely pathogenic (of 4,597 scored), across 557 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M443	9	0.989	1.000
M501	9	0.985	1.000
M186	9	0.982	0.999
M434	9	0.981	0.999
M256	9	0.946	0.999
M548	9	0.941	1.000
M487	9	0.935	1.000
D246	8	1.000	1.000
D248	8	1.000	1.000
D480	8	1.000	1.000
D484	8	1.000	1.000
N485	8	1.000	1.000
D498	8	1.000	1.000
H36	8	0.999	1.000
H74	8	0.999	1.000
D187	8	0.999	1.000
D254	8	0.999	1.000
D441	8	0.999	1.000
D537	8	0.999	1.000
H139	8	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Testicular Germ Cell Tumor)

Disease associations

OMIM: gene MIM:176980 | disease phenotypes: MIM:605361

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
spinocerebellar ataxia type 14	Definitive	Autosomal dominant	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Dystonia, chorea or related movement disorder, childhood onset	amber
Hereditary neuropathy	amber
Hereditary neuropathy or pain disorder	amber

Mondo (3): spinocerebellar ataxia type 14 (MONDO:0011540), hereditary ataxia (MONDO:0100309), frontotemporal dementia (MONDO:0017276)

Orphanet (3): Spinocerebellar ataxia type 14 (Orphanet:98763), Hereditary ataxia (Orphanet:183518), Frontotemporal dementia (Orphanet:282)

HPO phenotypes

30 phenotypes (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

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D057180	Frontotemporal Dementia	C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 287,227 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

23 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL1863513	INGENOL MEBUTATE	4	1,527
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	552
CHEMBL38380	FASUDIL	3	12,137
CHEMBL91829	RUBOXISTAURIN	3	78
CHEMBL265502	SURAMIN	3	37,133
CHEMBL1967878	CENISERTIB	2	373
CHEMBL3982723	DAROVASERTIB	2	503
CHEMBL28509	EDELFOSINE	2	10,657
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL362558	LY-2090314	2	109
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,427
CHEMBL475251	R-406	2	787
CHEMBL565612	SOTRASTAURIN	2	1,414
CHEMBL574737	UCN-01	2	2,319
CHEMBL3137336	UPROSERTIB	2	1,706
CHEMBL1084546	PF-00562271	1
CHEMBL3128043	PF-03758309	1
CHEMBL1980391	RG-1530	1

PharmGKB: 1 entry (CPIC guideline: no)

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)

400 measured of 521 human assays (544 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4442196	IC50	0.09 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL3741746	EC50	0.19 nM
CHEMBL4435580	IC50	0.22 nM
CHEMBL2148106	KI	0.26 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Aplysiatoxin	KI	0.4 nM
13-Hydroxymethyl-10-isopropyl-9-methyl-5-octyl-3,9,12-triaza-tricyclo[6.6.1.0*4,15*]pentadeca-1,4,6,8(15)-tetraen-11-one (n-octyl-ILV)	KI	0.5 nM
CHEMBL4587471	EC50	0.55 nM
CHEMBL4575056	EC50	0.6 nM
CHEMBL5175742	KI	0.65 nM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	IC50	1 nM	US-8530652: Pyrrolopyrazoles, potent kinase inhibitors
DEMETHOXYDEBROMOAPLYSIATOXIN	KI	1 nM
Compound K-252a(epi)	IC50	1.2 nM
CHEMBL83790	IC50	2.2 nM
corilagin	EC50	3.2 nM
23-ethyl-17,20-dioxa-4,14,23,26-tetraazahexacyclo[24.6.1.17,14.02,6.08,13.027,32]tetratriaconta-1(33),2(6),7(34),8(13),9,11,27(32),28,30-nonaene-3,5-dione	IC50	4 nM
3-(1-{2-[2-(2-Dimethylamino-ethoxy)-ethoxy]-ethyl}-1H-indol-3-yl)-4-(1-propyl-1H-indol-3-yl)-pyrrole-2,5-dione	IC50	4 nM
CHEMBL2148108	KI	4.7 nM
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	IC50	5.5 nM
3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
17,23-dimethyl-20-oxa-4,14,17,23,26-pentaazahexacyclo[24.6.1.17,14.02,6.08,13.027,32]tetratriaconta-1(33),2(6),7(34),8(13),9,11,27(32),28,30-nonaene-3,5-dione	IC50	6 nM
Staurosporine, 8	IC50	6.5 nM
NB-506 Analogue	EC50	8 nM
N-(3-{3-[4-(2-Methoxy-phenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-pyrrolo[2,3-b]pyridin-1-yl}-propyl)-formamide	IC50	8 nM
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
CHEMBL4465866	KD	8 nM
CHEMBL4576489	KD	8 nM
4-(2-Carboxy-6-hydroxy-benzoyl)-3,5-dihydroxy-benzoic acid (1R,2R,4S)-2-(4-hydroxy-benzoylamino)-4-hydroxymethyl-cyclopentyl ester	IC50	10 nM
3-(2-Chloro-phenyl)-4-[1-(3-hydroxy-propyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyrrole-2,5-dione	IC50	10 nM
CHEMBL329274	IC50	10 nM
4-(2-Carboxy-6-hydroxy-benzoyl)-3,5-dihydroxy-benzoic acid (3S,5R)-2-((S)-4-hydroxy-benzoylamino)-4-hydroxymethyl-cyclopentyl ester	IC50	10 nM
Butyric acid (1aR,1bS,4aS,7aR,7bR,8R,9R,9aS)-9-butyryloxy-7b-hydroxy-3-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	KI	14 nM
N-(3-{3-[4-(2-Methoxy-phenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-pyrrolo[2,3-b]pyridin-1-yl}-propyl)-methanesulfonamide	IC50	14 nM
8-Dec-1-ynyl-5-hydroxymethyl-2-isopropyl-1-methyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one	KI	15 nM
3-(2-Chloro-phenyl)-4-[1-(3-dimethylamino-propyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyrrole-2,5-dione	IC50	15 nM
CHEMBL2148107	KI	15 nM
[2-(Hydroxymethyl)-4-(methylethylidene)-5-oxo-2-2,3-dihydrofuryl]methyl 4-[2-(4-Methylphenyl)ethynyl]benzoate	KI	16 nM
CHEMBL4441825	IC50	16 nM
NB-506 Analogue	EC50	17 nM
3-methoxy-2-methyl-4-methylamino-(2S,3S,4S,6R)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8(13),9,11,14(28),15(19),20(27),21,23,25-nonaen-16-one	IC50	18 nM
(Rebeccamycin)1,11-dichloro-12-(3,4-dihydroxy-6-hydroxymethyl-5-methoxytetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	IC50	19 nM
4-(2-Carboxy-6-hydroxy-benzoyl)-3,5-dihydroxy-benzoic acid (1R,2R,4R)-4-amino-2-(4-hydroxy-benzoylamino)-cyclopentyl ester	IC50	20 nM
4-(2-Carboxy-6-hydroxy-benzoyl)-3,5-dihydroxy-benzoic acid (1R,2R,4S)-4-aminomethyl-2-(4-hydroxy-benzoylamino)-cyclopentyl ester	IC50	20 nM
4-(2-Carboxy-6-hydroxy-benzoyl)-3,5-dihydroxy-benzoic acid (1R,2R,4R)-4-aminomethyl-2-(4-hydroxy-benzoylamino)-cyclopentyl ester	IC50	20 nM
NB-506 Analogue	EC50	20 nM
3-(7-Azaindolyl)-4-arylmaleimide analogue	IC50	20 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

379 with measured affinity, of 2670 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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	decreases expression, increases activity, affects localization, decreases reaction	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
Tretinoin	increases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Sirolimus	increases degradation, affects binding, decreases reaction	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)

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

showing 60 of 297 trials:

NCT	Phase	Status	Title
NCT00950196	Phase 4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	Phase 4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT00376051	Phase 4	COMPLETED	Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
NCT00950430	Phase 4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT06093126	Phase 4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT01970098	Phase 3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	Phase 3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	Phase 3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	Phase 3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	Phase 3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	Phase 3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	Phase 3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	Phase 3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	Phase 3	ACTIVE_NOT_RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00594737	Phase 3	COMPLETED	Open Label Pilot Study of the Effects of Memantine on FDG-PET in Frontotemporal Dementia
NCT03682185	Phase 3	COMPLETED	The Healthy Patterns Sleep Study
NCT04374136	Phase 3	TERMINATED	A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)
NCT00034242	Phase 2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	Phase 2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	Phase 2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	Phase 2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	Phase 2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	Phase 2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	Phase 2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	Phase 2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	Phase 2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	Phase 2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00416169	Phase 2	COMPLETED	A Pilot Study to Explore the Safety and Tolerability of Galantamine HBr in the Treatment of Pick Complex/Frontotemporal Dementia
NCT01890343	Phase 2	COMPLETED	Imaging Characteristics of Florbetapir 18F in Patients With Frontotemporal Dementia, Alzheimer’s Disease and Normal Controls.
NCT01937013	Phase 2	COMPLETED	Impact of Emotional Mimicry and Oxytocin on Frontotemporal Dementia
NCT02676843	Phase 2	COMPLETED	Tau PET Imaging With 18F-AV-1451 in Subjects With MAPT Mutations
NCT02862210	Phase 2	COMPLETED	Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
NCT03260920	Phase 2	UNKNOWN	Intranasal Oxytocin for Frontotemporal Dementia
NCT03987295	Phase 2	COMPLETED	A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
NCT04220021	Phase 2	ACTIVE_NOT_RECRUITING	Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD
NCT04489017	Phase 2	COMPLETED	Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial
NCT04937452	Phase 2	COMPLETED	Dopaminergic Therapy for Frontotemporal Dementia Patients
NCT04993755	Phase 2	COMPLETED	A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD
NCT05742698	Phase 2	TERMINATED	Nabilone for Agitation in Frontotemporal Dementia
NCT06604520	Phase 2	RECRUITING	Vortioxetine for the Treatment of Mood and Cognitive Symptoms in Frontotemporal Dementia
NCT07154485	Phase 2	NOT_YET_RECRUITING	Investigator Initiated Study for the Safety and Efficacy in Frontotemporal Dementia
NCT00683943	Phase 1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	Phase 1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	Phase 1	UNKNOWN	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01386333	Phase 1	COMPLETED	Safety Study of Intranasal Oxytocin in Frontotemporal Dementia
NCT03040713	Phase 1	COMPLETED	Flortaucipir PET Imaging in Subjects With FTD
NCT03636204	Phase 1	COMPLETED	A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation
NCT05315661	Phase 1	ACTIVE_NOT_RECRUITING	The Safety and The Efficacy Evaluation of ET-STEM in Patients With Frontotemporal Dementia
NCT06705192	Phase 1	COMPLETED	Study in Asymptomatic GRN-FTD Patients to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01104649	Phase 2/3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893	Phase 2/3	COMPLETED	Trial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361	Phase 1/2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687	Phase 1/2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	Phase 1/2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268	Phase 1/2	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

Predicted chemistry — Sugi Predict

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