CAMK2G

Summary

CAMK2G (calcium/calmodulin dependent protein kinase II gamma, HGNC:1463) is a protein-coding gene on chromosome 10q22.2, encoding Calcium/calmodulin-dependent protein kinase type II subunit gamma (Q13555). Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal p….

The product of this gene is one of the four subunits of an enzyme which belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a gamma chain. Many alternatively spliced transcripts encoding different isoforms have been described but the full-length nature of all the variants has not been determined.

Source: NCBI Gene 818 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder 59 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 19
• Clinical variants (ClinVar): 139 total — 5 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes — 39 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001367534

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1463
Approved symbol	CAMK2G
Name	calcium/calmodulin dependent protein kinase II gamma
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000148660
Ensembl biotype	protein_coding
OMIM	602123
Entrez	818

Gene structure

Transcript identifiers

Ensembl transcripts: 101 — 87 protein_coding, 9 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000305762, ENST00000322635, ENST00000322680, ENST00000351293, ENST00000372765, ENST00000394762, ENST00000423381, ENST00000433289, ENST00000441192, ENST00000472912, ENST00000474131, ENST00000477205, ENST00000477652, ENST00000492020, ENST00000680035, ENST00000700392, ENST00000700393, ENST00000700394, ENST00000700395, ENST00000700396, ENST00000700397, ENST00000700398, ENST00000700399, ENST00000700400, ENST00000700401, ENST00000700402, ENST00000700403, ENST00000864107, ENST00000864108, ENST00000864109, ENST00000864110, ENST00000864111, ENST00000864112, ENST00000864113, ENST00000864114, ENST00000864115, ENST00000864116, ENST00000864117, ENST00000864118, ENST00000864119, ENST00000864120, ENST00000864121, ENST00000864122, ENST00000864123, ENST00000864124, ENST00000864125, ENST00000864126, ENST00000864127, ENST00000864128, ENST00000864129, ENST00000864130, ENST00000864131, ENST00000864132, ENST00000864133, ENST00000864134, ENST00000864135, ENST00000864136, ENST00000864137, ENST00000864138, ENST00000864139, ENST00000864140, ENST00000864141, ENST00000864142, ENST00000864143, ENST00000864144, ENST00000864145, ENST00000864146, ENST00000864147, ENST00000864148, ENST00000864149, ENST00000936899, ENST00000936900, ENST00000936901, ENST00000936902, ENST00000964824, ENST00000964825, ENST00000964826, ENST00000964827, ENST00000964828, ENST00000964829, ENST00000964830, ENST00000964831, ENST00000964832, ENST00000964833, ENST00000964834, ENST00000964835, ENST00000964836, ENST00000964837, ENST00000964838, ENST00000964839, ENST00000964840, ENST00000964841, ENST00000964842, ENST00000964843, ENST00000964844, ENST00000964845, ENST00000964846, ENST00000964847, ENST00000964848, ENST00000964849, ENST00000964850

RefSeq mRNA: 41 — MANE Select: NM_001367534 NM_001204492, NM_001222, NM_001320898, NM_001367514, NM_001367516, NM_001367517, NM_001367518, NM_001367519, NM_001367520, NM_001367521, NM_001367522, NM_001367523, NM_001367524, NM_001367525, NM_001367526, NM_001367527, NM_001367528, NM_001367529, NM_001367530, NM_001367531, NM_001367532, NM_001367533, NM_001367534, NM_001367535, NM_001367536, NM_001367537, NM_001367538, NM_001367539, NM_001367540, NM_001367541, NM_001367542, NM_001367543, NM_001367544, NM_001367545, NM_001367546, NM_001367547, NM_001367548, NM_172169, NM_172170, NM_172171, NM_172173

CCDS: CCDS73153, CCDS7336, CCDS7337, CCDS7338, CCDS91267, CCDS91269

Canonical transcript exons

ENST00000423381 — 23 exons

Exon	Start	End
ENSE00001183860	73853192	73853246
ENSE00001283184	73812501	73814505
ENSE00001283216	73828089	73828121
ENSE00003469895	73825279	73825347
ENSE00003475997	73849013	73849115
ENSE00003484607	73848526	73848609
ENSE00003494300	73842169	73842211
ENSE00003501034	73824040	73824084
ENSE00003535818	73819532	73819645
ENSE00003551234	73849261	73849333
ENSE00003553005	73817479	73817554
ENSE00003559715	73837468	73837511
ENSE00003566246	73817023	73817117
ENSE00003572211	73872989	73873083
ENSE00003582128	73847225	73847347
ENSE00003589418	73815003	73815247
ENSE00003594278	73852254	73852319
ENSE00003644649	73860830	73860889
ENSE00003656876	73839539	73839601
ENSE00003674799	73847988	73848082
ENSE00003676789	73842458	73842541
ENSE00003679507	73821682	73821730
ENSE00003911517	73874397	73874555

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5905 / max 465.3416, expressed in 1794 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110122	23.9364	1786
110123	3.9821	1281
110121	0.6721	376

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	97.96	gold quality
postcentral gyrus	UBERON:0002581	97.58	gold quality
right frontal lobe	UBERON:0002810	97.56	gold quality
popliteal artery	UBERON:0002250	97.54	gold quality
tibial artery	UBERON:0007610	97.54	gold quality
parietal lobe	UBERON:0001872	97.41	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.40	gold quality
prefrontal cortex	UBERON:0000451	97.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.33	gold quality
frontal cortex	UBERON:0001870	97.23	gold quality
right coronary artery	UBERON:0001625	97.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.13	gold quality
primary visual cortex	UBERON:0002436	97.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.12	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.01	gold quality
cingulate cortex	UBERON:0003027	96.99	gold quality
neocortex	UBERON:0001950	96.97	gold quality
anterior cingulate cortex	UBERON:0009835	96.97	gold quality
occipital lobe	UBERON:0002021	96.96	gold quality
paraflocculus	UBERON:0005351	96.91	gold quality
aorta	UBERON:0000947	96.84	gold quality
superior frontal gyrus	UBERON:0002661	96.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.70	gold quality
pons	UBERON:0000988	96.64	gold quality
orbitofrontal cortex	UBERON:0004167	96.54	gold quality
descending thoracic aorta	UBERON:0002345	96.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.40	gold quality
lower esophagus	UBERON:0013473	96.39	gold quality
blood vessel layer	UBERON:0004797	96.24	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.21	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	24.00
E-ANND-3	yes	8.89
E-MTAB-2983	no	539.91
E-ENAD-27	no	7.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting CAMK2G, 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-4283	100.00	66.42	2097
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1255A	99.74	68.09	744

Literature-anchored findings (GeneRIF, showing 40)

• role in cell communication (PMID:11889801)
• cloning, genomic structure and detection of variants in subjects with Type II diabetes (PMID:12032636)
• measured differences in CaMKII binding affinities for CaM play a minor role in the autophosphorylation of the enzyme, largely dictated by autophosphorylation rate for alpha, beta, gamma and delta isoforms (PMID:14722083)
• CaMKIIgamma is necessary to suppress MCAK depolymerase activity in vivo. (PMID:15775983)
• A transgenic, constitutively active, Ca2+-independent form of CaMKgamma reduces positive selection of T cells by maintaining association of SHP-2 with the T cell receptor (TCR) complex, and halting TCR signaling. (PMID:16002660)
• Amphetamine in a cell line induces a robust increase in cytosolic Ca2+ and concomitant activation of calcium/calmodulin-dependent protein kinase II (CaMKII). (PMID:17032905)
• Significant cross-talk between calcium and retinoic acid signaling pathways regulates the differentiation of myeloid leukemia cells. (PMID:17431504)
• insulin in the presence of Angiotensin II inhibits protein phosphatase-2A (PP-2A) and stimulates autonomous CaM kinase II activities and thus vascular smooth muscle migration (PMID:17553505)
• IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells. (PMID:18434368)
• CaMKIIgamma is a critical regulator of multiple signaling networks regulating the proliferation of myeloid leukemia cells (PMID:18483256)
• In Turner yndrome, loss of voltage-dependent inactivation is an upstream initiating event for arrhythmia phenotypes that are ultimately dependent on CaMKII activation. (PMID:19001023)
• increased RyR2-dependent Ca2+ leakage due to enhanced CaMKII activity is an important downstream effect of CaMKII in individuals susceptible to AF induction. (PMID:19603549)
• These data demonstrate that alphaKAP exhibits a novel interaction with SERCA2a and may serve to spatially position CaMKII isoforms at the SR and to uniquely modulate the phosphorylation of PLN. (PMID:19671701)
• P2X7 receptor-triggered signalling pathways that regulate neurite formation in neuroblastoma cells. (PMID:19682070)
• Study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism that involves inter-holoenzyme T286-region/T-site interaction. (PMID:19840793)
• The interaction between CaMKII and its binding proteins was altered by the phosphorylation state of both the CaMKII and the partner. (PMID:20060891)
• CaMKII is a molecular link translating intracellular calcium changes, which are intrinsically associated with glioma migration, to changes in ClC-3 conductance required for cell movement (PMID:20139089)
• Our results suggest a first observation that CaMKII regulates TRAIL-mediated apoptosis of fibroblast-like synovial cells through Akt, standing an upstream of caspase-8-dependent cascades. (PMID:20149311)
• These results indicated that PP6 and CaMKII regulated apoptosis by controlling the expression level of p27. (PMID:20851109)
• Ca(2+)/calmodulin-dependent kinase II participate in control of cell cycle progression and survival of irradiated CML cells. (PMID:21063097)
• study shows CaMKII is recruited to the immunological synapse where it interacts with and phosphorylates Bcl10; propose a mechanism whereby Ca(2+) signals can be integrated at the immunological synapse through CaMKII-dependent phosphorylation of Bcl10 (PMID:21513986)
• increases in Ca(2+) lead to CaMKII activation and subsequent Lck-dependent p66Shc phosphorylation on Serine 36. This event causes both mitochondrial dysfunction and impaired Ca(2+) homeostasis, which synergize in promoting Jurkat T-cell apoptosis. (PMID:21983898)
• study demonstrates that premitotic condensation involves the activation of ClC-3 by Ca(2+)/calmodulin-dependent protein kinase II in glioma cells (PMID:22049206)
• CaMKII binding to and phosphorylation of the NHE3 C terminus are parts of the physiologic regulation of NHE3 that occurs in fibroblasts as well as in the brush border of an intestinal Na(+)-absorptive cell. (PMID:22371496)
• CaMKII was also necessary for the phosphorylation of Raf-1 at S338 by serum, fibronectin and Ras. (PMID:22592532)
• we review the cellular colocalization of CaMKII isoforms with special regard to the cell-type specificity of isoform expression in brain–REVIEW (PMID:22612808)
• CaMKII T286A showed a mildly but significantly reduced rate of Ca(2+)/CaM-stimulated phosphorylation for two different peptide substrates (to ~75-84% of wild type). (PMID:22615928)
• These findings revealed a fundamental role of CaMKII in the enteric nervous system. (PMID:22952977)
• The CaMKII phosphorylation motif in the Nav1.5 DI-DII cytoplasmic loop is a critical point for proarrhythmic changes. (PMID:23008441)
• Data indicate that CaMKII gamma as a specific and critical target of berbamine for its antileukemia activity. (PMID:23074277)
• results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-kappaB in response to H. pylori infection (PMID:23463379)
• Activated CaMK-II interacts with the C-terminal domain of diacylglycerol lipase-alpha (DGLalpha) and inhibits DGLalpha activity. (PMID:23502535)
• the chronic gain-of-function defect in RyR2 due to CaMKII hyperphosphorylation is a novel mechanism that contributes to pathogenesis of type 2 diabetes (PMID:23516528)
• CaMKII overexpression in mushroom body neurons increases activity dependent calcium responses. (PMID:23543616)
• Our data suggest that berbamine and its derivatives are promising agents to suppress liver cancer growth by targeting CAMKII (PMID:23960096)
• it can be concluded that CaMKII regulates the activity of ASIC1, which is associated with the ability of GBM cells to migrate. (PMID:24100685)
• CAMKIIgamma, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease. (PMID:24206096)
• When inhibiting CaMKII, B-cell activating factor (BAFF) is attenuated and mediates protein phosphatase (PP)2A-Erk1/2 signaling and B-cell proliferation. (PMID:24269630)
• CaMKII-dependent microtube polymerization may be responsible for the enhanced uptake of PEI/ON complexes in A549 cells under oxidative stress conditions. (PMID:24634301)
• Inhibition of CaMKII activity results in an upregulation of CaMKIV mRNA and protein in leukemia cell lines. (PMID:25446257)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	camk2g2	ENSDARG00000056206
danio_rerio	camk2g1	ENSDARG00000071395
mus_musculus	Camk2g	ENSMUSG00000021820
rattus_norvegicus	Camk2g	ENSRNOG00000009783

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Calcium/calmodulin-dependent protein kinase type II subunit gamma — Q13555 (reviewed: Q13555)

All UniProt accessions (13): Q13555, A0A2Q3DQE3, A0A804CJ50, A0A8V8TPN2, A0A8V8TQ60, A0A8V8TQ77, A0A8V8TQ82, A0A8V8TQW6, A0A8V8TR68, A0A8V8TR72, H0Y6G2, Q5SWX3, Q8WU40

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin. In the central nervous system, it is involved in the regulation of neurite formation and arborization. It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway.

Subunit / interactions. CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other.

Subcellular location. Sarcoplasmic reticulum membrane.

Tissue specificity. Expressed in skeletal muscle.

Post-translational modifications. Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.

Disease relevance. Intellectual developmental disorder, autosomal dominant 59 (MRD59) [MIM:618522] An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.

Domain organisation. The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.

Induction. Activity is induced in skeletal muscle during exercise.

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

Isoforms (11)

UniProt ID	Names	Canonical?
Q13555-1	1	yes
Q13555-2	2
Q13555-3	3
Q13555-4	4
Q13555-5	5
Q13555-6	6
Q13555-7	7, gamma F
Q13555-8	8, gamma E
Q13555-9	9, gamma D
Q13555-10	10
Q13555-11	11

RefSeq proteins (41): NP_001191421, NP_001213, NP_001307827, NP_001354443, NP_001354445, NP_001354446, NP_001354447, NP_001354448, NP_001354449, NP_001354450, NP_001354451, NP_001354452, NP_001354453, NP_001354454, NP_001354455, NP_001354456, NP_001354457, NP_001354458, NP_001354459, NP_001354460, NP_001354461, NP_001354462, NP_001354463, NP_001354464, NP_001354465, NP_001354466, NP_001354467, NP_001354468, NP_001354469, NP_001354470, NP_001354471, NP_001354472, NP_001354473, NP_001354474, NP_001354475, NP_001354476, NP_001354477, NP_751909, NP_751910, NP_751911, NP_751913 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013543	Ca/CaM-dep_prot_kinase-assoc	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR032710	NTF2-like_dom_sf	Homologous_superfamily

Pfam: PF00069, PF08332

Enzyme classification (BRENDA):

• EC 2.7.11.17 — Ca2+/calmodulin-dependent protein kinase (BRENDA: 38 organisms, 300 substrates, 137 inhibitors, 35 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0071–178.29	13
BIOTINYLATED THR-ARG-SER-ALA-ILE-ARG-ARG-ALA-SER	0.0064–0.0158	4
GST-TAGGED GLUN2A	6.05–11.75	2
GST-TAGGED GLUN2B	0.35–5.93	2
MAP2	0.0007–0.0008	2
CALDESMON	0.0049	1
HISTONE IIIS	0.0445	1
LYS-LYS-ALA-LEU-ARG-ARG-GLN-GLU-ALA-VAL-ASP-ALA-	0.063	1
MICROTUBULE ASSOCIATED PROTEIN 2	0.0016	1
SYNTIDE-2	0.02	1
SYNTIDE-2 PEPTIDE	0.0221	1
MYELIN BASIC PROTEIN	—	0

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 (78 total): modified residue 20, helix 19, strand 13, splice variant 9, region of interest 4, turn 3, binding site 2, sequence variant 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2V7O	X-RAY DIFFRACTION	2.25
2UX0	X-RAY DIFFRACTION	2.46

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13555-F1	79.50	0.56

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): 136 (proton acceptor)

Ligand- & substrate-binding residues (2): 43; 20–28

Post-translational modifications (20): 287, 306, 307, 311, 334, 349, 352, 419, 484, 325, 325, 325, 325, 325, 325, 325, 338, 325, 325, 346

Function

Pathways and Gene Ontology

Reactome pathways

61 pathways

ID	Pathway
R-HSA-111932	CaMK IV-mediated phosphorylation of CREB
R-HSA-3371571	HSF1-dependent transactivation
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-442729	CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-5578775	Ion homeostasis
R-HSA-5673000	RAF activation
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-877300	Interferon gamma signaling
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9617324	Negative regulation of NMDA receptor-mediated neuronal transmission
R-HSA-9620244	Long-term potentiation
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-111885	Opioid Signalling
R-HSA-111933	Calmodulin induced events
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

MSigDB gene sets: 482 (showing top): PID_BCR_5PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, MORF_MSH3, REACTOME_CREB1_PHOSPHORYLATION_THROUGH_THE_ACTIVATION_OF_CAMKII_CAMKK_CAMKIV_CASCASDE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_SKELETAL_MUSCLE_ADAPTATION, GOBP_INSULIN_SECRETION, MORF_BRCA1, MORF_ATRX, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN

GO Biological Process (17): nervous system development (GO:0007399), regulation of neuron projection development (GO:0010975), regulation of skeletal muscle adaptation (GO:0014733), insulin secretion (GO:0030073), cell differentiation (GO:0030154), regulation of neuronal synaptic plasticity (GO:0048168), regulation of calcium ion transport (GO:0051924), long-term synaptic potentiation (GO:0060291), regulation of protein localization to plasma membrane (GO:1903076), response to hypoxia (GO:0001666), protein phosphorylation (GO:0006468), response to oxidative stress (GO:0006979), cell communication (GO:0007154), memory (GO:0007613), regulation of gene expression (GO:0010468), signaling (GO:0023052), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072)

GO Molecular Function (13): calcium/calmodulin-dependent protein kinase activity (GO:0004683), calcium-dependent protein serine/threonine phosphatase activity (GO:0004723), calmodulin binding (GO:0005516), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (13): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), calcium- and calmodulin-dependent protein kinase complex (GO:0005954), postsynaptic density (GO:0014069), membrane (GO:0016020), endocytic vesicle membrane (GO:0030666), sarcoplasmic reticulum membrane (GO:0033017), neuron projection (GO:0043005), sarcoplasmic reticulum (GO:0016529), axon (GO:0030424), glutamatergic synapse (GO:0098978), postsynaptic cytosol (GO:0099524)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
Oncogenic MAPK signaling	3
Post NMDA receptor activation events	2
Cardiac conduction	2
Calmodulin induced events	1
Cellular response to heat stress	1
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
RAF/MAP kinase cascade	1
MAPK1/MAPK3 signaling	1
Interferon Signaling	1
Transcriptional Regulation by MECP2	1
Ion channel transport	1
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of synaptic plasticity	2
response to stress	2
protein binding	2
protein kinase activity	2
bounding membrane of organelle	2
system development	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
skeletal muscle adaptation	1
regulation of muscle adaptation	1
protein secretion	1
peptide hormone secretion	1
cellular developmental process	1
calcium ion transport	1
regulation of metal ion transport	1
positive regulation of synaptic transmission	1
protein localization to plasma membrane	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
response to decreased oxygen levels	1
phosphorylation	1
protein modification process	1
cellular process	1
learning or memory	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of biological process	1
regulation of biological quality	1
protein serine/threonine kinase activity	1
protein serine/threonine phosphatase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

2762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMK2G	CALM1	P02593	982
CAMK2G	CALML3	P27482	982
CAMK2G	CALML5	Q9NZT1	982
CAMK2G	CALML6	Q8TD86	980
CAMK2G	CALML4	Q96GE6	980
CAMK2G	ADCY8	P40145	817
CAMK2G	GRIN2A	Q12879	804
CAMK2G	GRM3	Q14832	787
CAMK2G	CREB1	P16220	776
CAMK2G	GRIN2B	Q13224	769
CAMK2G	SYN3	O14994	663
CAMK2G	SYN2	Q92777	650
CAMK2G	LIN7A	O14910	609
CAMK2G	DLG4	P78352	595
CAMK2G	MED25	Q71SY5	589

IntAct

126 interactions, top by confidence:

A	B	Type	Score
MCM5	MCM3	psi-mi:“MI:0914”(association)	0.850
CAMK2G	CAMK2D	psi-mi:“MI:0407”(direct interaction)	0.810
CAMK2G	CAMK2D	psi-mi:“MI:0914”(association)	0.810
CAMK2A	CAMK2G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
CAMK2G	CALM1	psi-mi:“MI:0407”(direct interaction)	0.590
CAMK2G	CAMK2G	psi-mi:“MI:0407”(direct interaction)	0.560
RAC2	RAC1	psi-mi:“MI:0914”(association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NDUFA8	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NR3C1	BAG2	psi-mi:“MI:0914”(association)	0.530
TMEM200A	STX6	psi-mi:“MI:0914”(association)	0.530
CAMK2G	CAMK2B	psi-mi:“MI:0914”(association)	0.530
CAMK2D	ELP1	psi-mi:“MI:0914”(association)	0.530
TMEM200A	PPP3CB	psi-mi:“MI:0914”(association)	0.530
TPD52L1	TPD52L2	psi-mi:“MI:0914”(association)	0.530
CAMK2G	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
NR1H2	CAMK2G	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CAMK2G	ALOX5	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PCNA	CAMK2G	psi-mi:“MI:0915”(physical association)	0.370
CAMK2G	FXR1	psi-mi:“MI:0915”(physical association)	0.370
CAMK2G	FXR2	psi-mi:“MI:0915”(physical association)	0.370
Fto	CAMK2G	psi-mi:“MI:0915”(physical association)	0.370
	PLK4	psi-mi:“MI:0914”(association)	0.350
	CAMK2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (260): STMN1 (Biochemical Activity), CAMK2G (Affinity Capture-Western), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), DDX11 (Co-fractionation), PDLIM5 (Co-fractionation), SBDS (Co-fractionation), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAMK2G (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3S724, A4IGM9, A4IIW7, A5GFW1, B0VXL7, B6A7Q3, C0RW22, D7UQM5, F4I4F2, O08605, O14965, O35495, O55099, O59790, O70126, O80673, O94921, P18266, P27466, P49841, P59241, P97477, Q00771, Q0VD22, Q13555, Q16566, Q2TA06, Q501Q9, Q58D94, Q5XIT0, Q66JF3, Q6BVA0, Q6C3J2, Q6CWQ4, Q6DE08, Q6DGS3, Q6GPL3, Q6Z8C8, Q755C4, Q7YRC6

Diamond homologs: A0A2I0BVG8, A0A509AFG4, A0A509AHB6, A0A509AQE6, A0A5K1K8H0, A0AAR7, A2ZVI7, A5A7I7, A5A7I8, B9FKW9, O49717, O70150, O77708, P08414, P11730, P13234, P15791, P28582, P28583, P49101, P53682, P53683, P53684, P62343, P62344, P62345, P93759, Q00168, Q06850, Q07250, Q0DYK7, Q13555, Q13557, Q14012, Q16566, Q1PFH8, Q2QQR2, Q2QVG8, Q2QX45, Q2QY37

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
CAMK2G	down-regulates	NCOR2	phosphorylation
calcium(2+)	up-regulates	CAMK2G	“chemical activation”
CAMK2G	“down-regulates activity”	ADCY3	phosphorylation
CAMK2G	“down-regulates activity”	EGFR	phosphorylation
CAMK2G	“down-regulates activity”	Adenylate_cyclase	phosphorylation
CAMK2G	“up-regulates activity”	SCN5A	phosphorylation
CAMK2G	“up-regulates activity”	SCN8A	phosphorylation
CAMK2G	“down-regulates activity”	FBXO43	phosphorylation
CAMK2G	down-regulates	HDAC5	phosphorylation
CAMK2G	up-regulates	MAP3K7	phosphorylation
CAMK2G	“up-regulates activity”	ATF1	phosphorylation
CAMK2G	“up-regulates activity”	CHAT	phosphorylation
CAMK2G	unknown	FLNA	phosphorylation
CAMK2G	“up-regulates activity”	GRIA1	phosphorylation
CAMK2G	unknown	GRIA4	phosphorylation
CAMK2G	“down-regulates activity”	MYLK	phosphorylation
CAMK2G	unknown	PEA15	phosphorylation
CAMK2G	unknown	PLCB3	phosphorylation
CAMK2G	unknown	RRAD	phosphorylation
CAMK2G	unknown	RYR1	phosphorylation
CAMK2G	unknown	SPR	phosphorylation
CAMK2G	“up-regulates activity”	STAT1	phosphorylation
CAMK2G	unknown	SYN1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	31.4×	7e-05
Signaling by RAS mutants	6	23.7×	6e-05
RAF activation	6	18.8×	1e-04
Cellular response to heat stress	5	18.4×	3e-04
RHO GTPases activate PKNs	6	17.8×	1e-04
Phase 0 - rapid depolarisation	5	16.2×	5e-04
Signaling by RAF1 mutants	6	15.6×	2e-04
HSF1-dependent transactivation	5	14.8×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic pattern recognition receptor signaling pathway	5	32.1×	1e-04
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	5	24.4×	2e-04
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	5	24.4×	2e-04
G2/M transition of mitotic cell cycle	7	15.8×	1e-04
long-term synaptic potentiation	7	14.2×	1e-04
substantia nigra development	5	13.3×	3e-03
protein phosphorylation	12	5.9×	2e-04
intracellular signal transduction	13	3.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	5
Uncertain significance	88
Likely benign	15
Benign	8

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1687297	NM_001367534.1(CAMK2G):c.969dup (p.Ala324fs)	Likely pathogenic
1710167	NM_001367534.1(CAMK2G):c.676A>G (p.Ile226Val)	Likely pathogenic
2580804	NM_001367534.1(CAMK2G):c.889C>T (p.Arg297Trp)	Likely pathogenic
3068000	NM_001367534.1(CAMK2G):c.1236T>A (p.Asp412Glu)	Likely pathogenic
4690251	NM_001367534.1(CAMK2G):c.173_174del (p.Leu58fs)	Likely pathogenic

SpliceAI

3960 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73817022:CGATT:C	donor_gain	1.0000
10:73817473:A:AC	donor_gain	1.0000
10:73817474:C:CC	donor_gain	1.0000
10:73817474:CTT:C	donor_loss	1.0000
10:73817474:CTTA:C	donor_gain	1.0000
10:73817475:TTA:T	donor_loss	1.0000
10:73817476:TACGT:T	donor_loss	1.0000
10:73817477:A:AC	donor_gain	1.0000
10:73817477:A:C	donor_loss	1.0000
10:73817478:C:CT	donor_gain	1.0000
10:73817478:CG:C	donor_gain	1.0000
10:73817478:CGT:C	donor_gain	1.0000
10:73817478:CGTG:C	donor_gain	1.0000
10:73817478:CGTGT:C	donor_gain	1.0000
10:73817550:TCGCA:T	acceptor_gain	1.0000
10:73817551:CGCA:C	acceptor_gain	1.0000
10:73817551:CGCAC:C	acceptor_gain	1.0000
10:73817552:GCA:G	acceptor_gain	1.0000
10:73817553:CA:C	acceptor_gain	1.0000
10:73817553:CAC:C	acceptor_gain	1.0000
10:73817554:ACTG:A	acceptor_loss	1.0000
10:73817555:C:CC	acceptor_gain	1.0000
10:73817555:CTGT:C	acceptor_loss	1.0000
10:73817557:G:C	acceptor_gain	1.0000
10:73817557:G:GC	acceptor_gain	1.0000
10:73821679:TACC:T	donor_loss	1.0000
10:73821680:A:AT	donor_loss	1.0000
10:73821731:C:CC	acceptor_gain	1.0000
10:73824035:CTCA:C	donor_loss	1.0000
10:73824036:TCACC:T	donor_loss	1.0000

AlphaMissense

3886 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73815068:A:G	W542R	1.000
10:73815068:A:T	W542R	1.000
10:73815089:A:G	W535R	1.000
10:73815089:A:T	W535R	1.000
10:73815091:A:T	V534D	1.000
10:73815094:C:G	R533P	1.000
10:73815151:A:G	L514P	1.000
10:73815154:C:G	R513P	1.000
10:73815163:G:T	A510D	1.000
10:73815164:C:G	A510P	1.000
10:73815168:G:C	C508W	1.000
10:73815170:A:G	C508R	1.000
10:73815196:A:T	V499D	1.000
10:73815202:G:T	P497Q	1.000
10:73815204:G:C	N496K	1.000
10:73815204:G:T	N496K	1.000
10:73815208:A:G	L495P	1.000
10:73817046:A:G	F474S	1.000
10:73817064:A:G	L468P	1.000
10:73817070:C:T	G466D	1.000
10:73817071:C:G	G466R	1.000
10:73817108:A:C	C453W	1.000
10:73817510:C:G	A440P	1.000
10:73817518:A:G	L437P	1.000
10:73842201:A:G	L305P	1.000
10:73842210:C:T	G302D	1.000
10:73842211:C:G	G302R	1.000
10:73842462:A:G	L300P	1.000
10:73842467:T:A	R298S	1.000
10:73842467:T:G	R298S	1.000

dbSNP variants (sampled 300 via entrez): RS1000002170 (10:73837405 A>C,G), RS1000068579 (10:73842221 G>A,C), RS1000089106 (10:73841322 G>A,C), RS1000185058 (10:73817772 C>A,T), RS1000217266 (10:73843033 C>G,T), RS1000237191 (10:73818021 C>T), RS1000244416 (10:73860337 G>C), RS1000261127 (10:73825095 G>A), RS1000296603 (10:73860633 C>T), RS1000434470 (10:73853850 T>C), RS1000438135 (10:73841091 G>A), RS1000505613 (10:73843344 G>T), RS1000539862 (10:73862444 T>C,G), RS1000566187 (10:73865184 T>C), RS1000568049 (10:73823426 A>G)

Disease associations

OMIM: gene MIM:602123 | disease phenotypes: MIM:618522, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder 59	Strong	Autosomal dominant
genetic developmental and epileptic encephalopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual developmental disorder 59	Limited	AD

Mondo (4): intellectual developmental disorder 59 (MONDO:0032795), neurodevelopmental disorder (MONDO:0700092), autism (MONDO:0005260), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000256	Macrocephaly
HP:0000297	Facial hypotonia
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0000637	Long palpebral fissure
HP:0000742	Self-mutilation
HP:0000750	Delayed speech and language development
HP:0000960	Sacral dimple
HP:0001156	Brachydactyly
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001773	Short foot
HP:0001808	Fragile nails
HP:0002465	Poor speech
HP:0002553	Highly arched eyebrow
HP:0003502	Mild short stature
HP:0003593	Infantile onset
HP:0004279	Short palm
HP:0004322	Short stature
HP:0004425	Flat forehead
HP:0010864	Severe intellectual disability
HP:0012368	Flat face
HP:0000717	Autism

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST002889_5	Psoriasis	2.000000e-14
GCST003268_4	Psoriasis vulgaris	4.000000e-11
GCST003268_8	Psoriasis vulgaris	3.000000e-08
GCST004132_74	Crohn’s disease	2.000000e-09
GCST004865_96	Itch intensity from mosquito bite adjusted by bite size	9.000000e-06
GCST005352_12	Paclitaxel disposition in epithelial ovarian cancer	8.000000e-06
GCST006867_109	Type 2 diabetes	2.000000e-08
GCST007400_26	Systemic lupus erythematosus	7.000000e-06
GCST007429_141	Lung function (FVC)	8.000000e-12
GCST007430_47	Peak expiratory flow	6.000000e-10
GCST007430_82	Peak expiratory flow	2.000000e-07
GCST007431_12	Lung function (FEV1/FVC)	4.000000e-14
GCST007431_157	Lung function (FEV1/FVC)	6.000000e-11
GCST007432_188	FEV1	3.000000e-21
GCST007432_40	FEV1	8.000000e-10
GCST007656_13	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-10
GCST009597_167	Multiple sclerosis	5.000000e-08
GCST010989_86	Body size at age 10	9.000000e-09
GCST90013407_60	Liver enzyme levels (gamma-glutamyl transferase)	7.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2097164 (PROTEIN FAMILY), CHEMBL3829 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

39 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 319,968 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL3545396	BMS-690514	2
CHEMBL362558	LY-2090314	2
CHEMBL384304	RG-547	2
CHEMBL475251	R-406	2
CHEMBL513909	BI-2536	2
CHEMBL565612	SOTRASTAURIN	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CAMK2 family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
bosutinib	Inhibition	6.74	pIC50

Binding affinities (BindingDB)

6 measured of 7 human assays (7 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
(3R,4R)-3-methoxy-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	3.93 nM	US-10189849: CDK inhibitors
PKC-412	KD	190 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

336 potent at pChembl≥5 of 347 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.44	IC50	0.366	nM	STAUROSPORINE
9.41	IC50	0.387	nM	STAUROSPORINE
9.30	Kd	0.5	nM	STAUROSPORINE
9.26	Kd	0.55	nM	STAUROSPORINE
9.18	IC50	0.656	nM	STAUROSPORINE
9.15	IC50	0.7	nM	CHEMBL3683258
9.10	IC50	0.79	nM	CHEMBL4556306
8.70	IC50	2	nM	STAUROSPORINE
8.40	IC50	4	nM	STAUROSPORINE
8.40	Ki	3.981	nM	CHEMBL1974870
8.40	Ki	3.981	nM	CHEMBL1966628
8.22	IC50	6	nM	STAUROSPORINE
8.10	Kd	8	nM	CHEMBL4465866
8.05	Kd	9	nM	CHEMBL4576489
8.00	Ki	10	nM	CHEMBL1998159
7.95	Kd	11.22	nM	CHEMBL5653589
7.90	Ki	12.59	nM	TAE-684
7.90	Ki	12.59	nM	CHEMBL1970903
7.80	Ki	15.85	nM	CHEMBL1991063
7.75	Kd	18	nM	ABEMACICLIB
7.60	IC50	25	nM	CHEMBL312292
7.60	IC50	25	nM	STAUROSPORINE AGLYCON
7.60	Ki	25.12	nM	CHEMBL2001751
7.60	Ki	25.12	nM	CHEMBL2002726
7.58	Kd	26	nM	LESTAURTINIB
7.50	IC50	32	nM	CHEMBL2369378
7.50	Ki	31.62	nM	CHEMBL1986943
7.44	IC50	36	nM	CHEMBL385035
7.42	Kd	38.37	nM	CHEMBL3752910
7.40	Ki	39.81	nM	CHEMBL1990885
7.40	Ki	39.81	nM	CHEMBL1993661
7.34	IC50	46	nM	CHEMBL75368
7.32	IC50	48	nM	BRIGATINIB
7.32	IC50	48	nM	CHEMBL6165880
7.31	IC50	49	nM	CHEMBL73764
7.30	Ki	50.12	nM	CHEMBL1965836
7.30	Ki	50.12	nM	CHEMBL1982957
7.30	Ki	50.12	nM	CHEMBL1996817
7.29	ED50	51.67	nM	CHEMBL5653589
7.28	IC50	52	nM	ABEMACICLIB
7.24	IC50	58	nM	CHEMBL59785
7.21	IC50	62	nM	CHEMBL307630
7.20	Ki	63.1	nM	CHEMBL1987034
7.10	Ki	79.43	nM	SOTRASTAURIN
7.10	Ki	79.43	nM	CHEMBL1995813
7.09	IC50	82	nM	CHEMBL292021
7.09	IC50	81	nM	CHEMBL72808
7.05	IC50	90	nM	CHEMBL308979
7.04	IC50	92	nM	CHEMBL293157
7.02	IC50	95	nM	CHEMBL76326

PubChem BioAssay actives

112 with measured affinity, of 1861 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
(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	1531611: Inhibition of human CAMK2G using KKLNRTLSFAEPG as substrate by [gamma-33P]-ATP assay	ic50	0.0004	uM
N-(4-cycloheptyl-4-oxobutyl)-4-methoxy-N-phenylbenzenesulfonamide	1876293: Inhibition of CamK-II (unknown origin)	ic50	0.0008	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526223: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged CAMK2G (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr in presence of calmodulin by TR-FRET assay	kd	0.0080	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526223: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged CAMK2G (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr in presence of calmodulin by TR-FRET assay	kd	0.0090	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147985: Binding affinity to human CAMK2G incubated for 45 mins by Kinobead based pull down assay	kd	0.0112	uM
Abemaciclib	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0180	uM
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-nonaene-12,14-dione	45962: Inhibition of Calcium/calmodulin-dependent protein kinase type II	ic50	0.0250	uM
1-[2-(18-methyl-12,14-dioxo-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaen-5-yl)ethyl]piperidine-4-carboxamide	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0250	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-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-nonaen-3-one	507858: Binding affinity to CAMK2G	kd	0.0260	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-6-[(2-nitrophenyl)methoxycarbonylamino]hexanoyl]amino]-6-[(2-nitrophenyl)methoxycarbonylamino]hexanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	220482: Inhibitory activity of compound against CaMKII	ic50	0.0320	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[(2-nitrophenyl)methoxycarbonylamino]hexanoyl]amino]hexanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-4-methylpentanoic acid	220482: Inhibitory activity of compound against CaMKII	ic50	0.0360	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147985: Binding affinity to human CAMK2G incubated for 45 mins by Kinobead based pull down assay	kd	0.0384	uM
5-[2-(4-hydroxypiperidin-1-yl)ethyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0460	uM
Brigatinib	2182806: Inhibition of human CAMK2G using KKLNRTLSFAEPG as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0480	uM
5-[2-[(4-hydroxycyclohexyl)amino]ethyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0490	uM
8-bromo-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaene-12,14-dione	45967: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II using autocamtide as substrate	ic50	0.0580	uM
18-methyl-5-(2-piperidin-1-ylethyl)-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0620	uM
methyl 1-[2-(18-methyl-12,14-dioxo-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaen-5-yl)ethyl]piperidine-4-carboxylate	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0810	uM
6-methyl-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaene-12,14-dione	45967: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II using autocamtide as substrate	ic50	0.0820	uM
5-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0900	uM
6-fluoro-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaene-12,14-dione	45967: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II using autocamtide as substrate	ic50	0.0920	uM
5-[2-(2-hydroxyethylamino)ethyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.0950	uM
Ruxolitinib	624731: Binding constant for CAMK2G kinase domain	kd	0.1000	uM
Midostaurin	435784: Binding constant for CAMK2G kinase domain	kd	0.1400	uM
Gilteritinib	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1690	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-16-carboxylate	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1730	uM
20-bromo-3-methyl-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17(22),18,20-nonaene-12,14-dione	45967: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II using autocamtide as substrate	ic50	0.1740	uM
5-[3-(diethylamino)propyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.1740	uM
18-methyl-5-(2-morpholin-4-ylethyl)-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.1770	uM
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-12-one	45962: Inhibition of Calcium/calmodulin-dependent protein kinase type II	ic50	0.1840	uM
Bosutinib	507452: Inhibition of CAMK2G	ic50	0.1840	uM
5-[3-[(4-hydroxycyclohexyl)amino]propyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.2160	uM
6-methoxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaene-12,14-dione	45967: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II using autocamtide as substrate	ic50	0.2360	uM
Baricitinib	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2430	uM
Ribociclib	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2470	uM
5-[3-(2-hydroxyethylamino)propyl]-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.2660	uM
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	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2750	uM
18-methyl-5-(2-piperazin-1-ylethyl)-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.3010	uM
18-methyl-5-[3-(4-methylpiperazin-1-yl)propyl]-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.3820	uM
18-methyl-5-(2-thiomorpholin-4-ylethyl)-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.4030	uM
Sunitinib	507854: Binding affinity to CAMK1G	kd	0.4400	uM
18-methyl-5-(3-morpholin-4-ylpropyl)-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.5160	uM
3-[2-(2-hydroxyethylamino)ethyl]-6-methoxy-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.5270	uM
Fedratinib	624731: Binding constant for CAMK2G kinase domain	kd	0.5400	uM
Momelotinib	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5970	uM
3-[3-(2-hydroxyethylamino)propyl]-6-methoxy-18-methyl-3,13,18-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17(21),19,22-nonaene-12,14-dione	45968: Inhibitory activity against Calcium/calmodulin-dependent protein kinase type II	ic50	0.7320	uM
(3R,4R)-4-amino-1-[[4-(3-methoxyanilino)pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.7380	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1424929: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.7660	uM
20-ethyl-17,23-dioxa-4,14,20,26-tetrazahexacyclo[24.6.1.17,14.02,6.08,13.027,32]tetratriaconta-1(33),2(6),7(34),8,10,12,27,29,31-nonaene-3,5-dione	45969: Inhibition of Calcium/calmodulin-dependent protein kinase type II	ic50	0.7800	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624731: Binding constant for CAMK2G kinase domain	kd	0.7800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Tretinoin	decreases reaction, increases expression, affects binding	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
beta-methylcholine	affects expression	1
KN 62	decreases activity, decreases phosphorylation	1
cilnidipine	increases cleavage, increases reaction, decreases reaction	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Amphotericin B	increases expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	decreases expression	1
Estradiol	affects expression	1

ChEMBL screening assays

291 unique, capped per target: 290 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2422678	Binding	Inhibition of CaMK2alpha/CaMK2beta/CaMK2delta/CaMK2gamma in human PC3 cell lysates at 10 uM using desthiobiotin-tagged ATP probe AX9989 followed by trypsinization by LC/MS analysis	Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors. — Bioorg Med Chem Lett
CHEMBL1963710	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CAMK2G	PubChem BioAssay data set

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B1M1	Abcam HeLa CAMK2G KO	Cancer cell line	Female
CVCL_D7LL	Ubigene A-549 CAMK2G KO	Cancer cell line	Male
CVCL_D8IC	Ubigene HCT 116 CAMK2G KO	Cancer cell line	Male
CVCL_D9AW	Ubigene HEK293 CAMK2G KO	Transformed cell line	Female
CVCL_D9Z9	Ubigene HeLa CAMK2G KO	Cancer cell line	Female
CVCL_SG67	HAP1 CAMK2G (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
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NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
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NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
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NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
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NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
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NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents