CAMK1G

Summary

CAMK1G (calcium/calmodulin dependent protein kinase IG, HGNC:14585) is a protein-coding gene on chromosome 1q32.2, encoding Calcium/calmodulin-dependent protein kinase type 1G (Q96NX5). Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade.

Predicted to enable calcium/calmodulin-dependent protein kinase activity and calmodulin binding activity. Predicted to be involved in signal transduction. Predicted to be located in Golgi membrane and plasma membrane. Predicted to be part of calcium- and calmodulin-dependent protein kinase complex. Predicted to be active in cytoplasm.

Source: NCBI Gene 57172 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 87 total
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14585
Approved symbol	CAMK1G
Name	calcium/calmodulin dependent protein kinase IG
Location	1q32.2
Locus type	gene with protein product
Status	Approved
Aliases	VWS1, CLICKIII, dJ272L16.1
Ensembl gene	ENSG00000008118
Ensembl biotype	protein_coding
OMIM	614994
Entrez	57172

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000009105, ENST00000361322, ENST00000423146, ENST00000494990, ENST00000651530, ENST00000900039, ENST00000931514

RefSeq mRNA: 1 — MANE Select: NM_020439 NM_020439

CCDS: CCDS1486

Canonical transcript exons

ENST00000361322 — 13 exons

Exon	Start	End
ENSE00000476632	209594955	209595075
ENSE00000792078	209599983	209600111
ENSE00000792079	209603214	209603288
ENSE00000792081	209606320	209606443
ENSE00000792086	209611792	209612216
ENSE00001164873	209605536	209605674
ENSE00001167104	209612785	209612912
ENSE00001777806	209607858	209607933
ENSE00003511719	209609851	209609929
ENSE00003528180	209611465	209611552
ENSE00003675261	209608980	209609092
ENSE00003842446	209613040	209613939
ENSE00003845237	209583714	209583772

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 92.51.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5227 / max 848.0818, expressed in 581 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8313	4.0013	446
8314	0.2170	71
8317	0.1387	68
8316	0.0841	39
8315	0.0816	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	92.51	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.44	gold quality
right frontal lobe	UBERON:0002810	91.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.01	gold quality
prefrontal cortex	UBERON:0000451	90.96	gold quality
cingulate cortex	UBERON:0003027	90.64	gold quality
anterior cingulate cortex	UBERON:0009835	90.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.31	gold quality
nucleus accumbens	UBERON:0001882	90.22	gold quality
frontal cortex	UBERON:0001870	90.08	gold quality
diaphragm	UBERON:0001103	89.22	gold quality
neocortex	UBERON:0001950	89.13	gold quality
middle frontal gyrus	UBERON:0002702	87.54	gold quality
CA1 field of hippocampus	UBERON:0003881	87.29	silver quality
superior frontal gyrus	UBERON:0002661	87.25	gold quality
putamen	UBERON:0001874	87.22	gold quality
cerebral cortex	UBERON:0000956	87.13	gold quality
caudate nucleus	UBERON:0001873	87.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.82	gold quality
telencephalon	UBERON:0001893	86.35	gold quality
middle temporal gyrus	UBERON:0002771	86.09	gold quality
stromal cell of endometrium	CL:0002255	85.52	gold quality
metanephros cortex	UBERON:0010533	84.71	gold quality
type B pancreatic cell	CL:0000169	84.36	gold quality
forebrain	UBERON:0001890	84.33	gold quality
orbitofrontal cortex	UBERON:0004167	83.52	gold quality
olfactory bulb	UBERON:0002264	83.40	gold quality
left ovary	UBERON:0002119	83.33	gold quality
postcentral gyrus	UBERON:0002581	83.20	gold quality
parietal lobe	UBERON:0001872	82.81	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting CAMK1G, 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-4455	100.00	65.48	1587
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-3922-3P	99.25	64.96	1136

Literature-anchored findings (GeneRIF, showing 4)

• CLICK-III/CaMKIgamma is a novel membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase (CaMK). (PMID:12637513)
• Calmodulin suppresses synaptotagmin-2 transcription in cortical neurons (PMID:20729199)
• Two new susceptibility loci for amyotrophic lateral sclerosis in the Han Chinese population in chromosome 1, CAMK1G and chromosome 22, SUSD2 and CABIN1. (PMID:23624525)
• No evidence of association between polymorphisms in CAMK1G and sporadic amyotrophic lateral sclerosis in Han Chinese (PMID:25677198)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	camk1gb	ENSDARG00000008788
danio_rerio	camk1ga	ENSDARG00000044526
mus_musculus	Camk1g	ENSMUSG00000016179
rattus_norvegicus	Camk1g	ENSRNOG00000006470

Paralogs (22): CAMKK1 (ENSG00000004660), 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), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Calcium/calmodulin-dependent protein kinase type 1G — Q96NX5 (reviewed: Q96NX5)

Alternative names: CaM kinase I gamma, CaMK-like CREB kinase III

All UniProt accessions (3): Q96NX5, A0A494C109, C9IYV2

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates transcription factor CREB1.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cell membrane.

Tissue specificity. Mainly expressed in brain with small amounts in skeletal muscles, kidney, spleen and liver. Strongly expressed in forebrain neocortex, striatum and limbic system.

Post-translational modifications. May be prenylated on Cys-473.

Activity regulation. Activated by Ca(2+)/calmodulin. Binding of calmodulin is thought to result in a conformational change and leads to activation through phosphorylation by CAMKK1.

Domain organisation. The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96NX5-1	1	yes
Q96NX5-2	2

RefSeq proteins (1): NP_065172* (*=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
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069

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 (39 total): helix 12, strand 8, turn 5, sequence variant 3, region of interest 3, binding site 2, chain 1, domain 1, sequence conflict 1, compositionally biased region 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JAM	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NX5-F1	67.61	0.40

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): 143 (proton acceptor)

Ligand- & substrate-binding residues (2): 29–37; 52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, BIOCARTA_FMLP_PATHWAY, MODULE_99, BIOCARTA_PGC1A_PATHWAY, BIOCARTA_HDAC_PATHWAY, SOX5_01, BLALOCK_ALZHEIMERS_DISEASE_DN, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_CALCIUM_CALMODULIN_DEPENDENT_PROTEIN_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, GOMF_ADENYL_NUCLEOTIDE_BINDING, BROWNE_HCMV_INFECTION_16HR_DN, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (2): signal transduction (GO:0007165), protein phosphorylation (GO:0006468)

GO Molecular Function (11): calcium/calmodulin-dependent protein kinase activity (GO:0004683), calmodulin binding (GO:0005516), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), 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 (7): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), plasma membrane (GO:0005886), calcium- and calmodulin-dependent protein kinase complex (GO:0005954), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein kinase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phosphorylation	1
protein modification process	1
protein serine/threonine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
intracellular protein-containing complex	1
catalytic complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

2072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMK1G	CALM1	P02593	791
CAMK1G	KCNN2	Q9H2S1	767
CAMK1G	MAP6D1	Q9H9H5	449
CAMK1G	CYP11B2	P19099	441
CAMK1G	PAXBP1	Q9Y5B6	440
CAMK1G	COMTD1	Q86VU5	438
CAMK1G	CACNA1F	O60840	437
CAMK1G	DUS2	Q9NX74	429
CAMK1G	TMC4	Q7Z404	421
CAMK1G	CALML3	P27482	419
CAMK1G	CALML5	Q9NZT1	419
CAMK1G	COPRS	Q9NQ92	418
CAMK1G	RIMBP2	O15034	416
CAMK1G	SYN2	Q92777	415
CAMK1G	AP3B2	Q13367	412

IntAct

31 interactions, top by confidence:

A	B	Type	Score
KRTAP10-8	CAMK1G	psi-mi:“MI:0915”(physical association)	0.560
	CAMK1G	psi-mi:“MI:0915”(physical association)	0.560
FLNA	CAMK1G	psi-mi:“MI:0915”(physical association)	0.560
GRN	CAMK1G	psi-mi:“MI:0915”(physical association)	0.560
MAT2A	CAMK1G	psi-mi:“MI:0915”(physical association)	0.560
CAMK1G	WFS1	psi-mi:“MI:0915”(physical association)	0.560
KIF1B	CAMK1G	psi-mi:“MI:0915”(physical association)	0.560
CAMK1G	RFWD3	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	CAMK1G	psi-mi:“MI:0915”(physical association)	0.400
CDC45	CAMK1G	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D		psi-mi:“MI:0914”(association)	0.350
CAMK1	PSMD12	psi-mi:“MI:0914”(association)	0.350
CAMK1D	CALM1	psi-mi:“MI:0914”(association)	0.350
	CAMK1G	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): CAMK1G (Affinity Capture-MS), ZBTB44 (Affinity Capture-MS), CAMK1G (Affinity Capture-MS), RFWD3 (Affinity Capture-MS), CAMK1G (Biochemical Activity), PIK3CA (Negative Genetic), CD22 (Positive Genetic), EPHA2 (Positive Genetic), MAP2K5 (Positive Genetic), KSR1 (Positive Genetic), KRTAP10-8 (Two-hybrid), KRTAP10-1 (Two-hybrid), CAMK1G (Affinity Capture-MS), ZBTB44 (Affinity Capture-MS), RFWD3 (Affinity Capture-MS)

ESM2 similar proteins: A0AUV4, A1A5Q6, A1A5R7, A2KF29, B1WAS2, C0HKC8, C0HKC9, D3ZML2, O60285, O74536, O88831, O88866, P41279, P51956, P57058, P97756, Q20443, Q2T9U5, Q5R7G9, Q5XHI9, Q60670, Q63562, Q641K5, Q66HE5, Q68UT7, Q6P431, Q6VZ17, Q7T0B0, Q7T0B1, Q7TNJ7, Q7TNL4, Q8BHI9, Q8BZN4, Q8C078, Q8C0N0, Q8C0V7, Q8C0X8, Q8CIP4, Q8IY84, Q8K4K4

Diamond homologs: A0A2I0BVG8, A0A509AFG4, A0A509AHB6, A0A509ALV6, A0A509AQE6, A0A5K1K8H0, A0AAR7, A5A7I7, A5A7I8, A8WXF6, O15865, O49717, O70150, P25323, P28582, P28583, P34101, P49101, P53681, P53682, P53683, P53684, P62343, P62344, P62345, P93759, Q06850, Q0D715, Q0DYK7, Q10KY3, Q1PE17, Q1PFH8, Q2QQR2, Q2QVG8, Q2QX45, Q38868, Q38869, Q38870, Q38871, Q38872

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CAMK1G	up-regulates	EIF4G3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1778 predictions. Top by Δscore:

Variant	Effect	Δscore
1:209594939:A:AG	acceptor_gain	1.0000
1:209594940:C:G	acceptor_gain	1.0000
1:209594945:T:A	acceptor_gain	1.0000
1:209594948:A:AG	acceptor_gain	1.0000
1:209594949:A:G	acceptor_gain	1.0000
1:209594951:A:AG	acceptor_gain	1.0000
1:209594952:A:G	acceptor_gain	1.0000
1:209594953:A:AG	acceptor_gain	1.0000
1:209594954:G:GG	acceptor_gain	1.0000
1:209595062:G:GT	donor_gain	1.0000
1:209595062:G:T	donor_gain	1.0000
1:209595071:GGATC:G	donor_gain	1.0000
1:209595072:GATC:G	donor_gain	1.0000
1:209595072:GATCG:G	donor_gain	1.0000
1:209595073:ATC:A	donor_gain	1.0000
1:209595074:TC:T	donor_gain	1.0000
1:209595076:G:GG	donor_gain	1.0000
1:209599981:A:AG	acceptor_gain	1.0000
1:209599981:AGAG:A	acceptor_gain	1.0000
1:209599982:G:GG	acceptor_gain	1.0000
1:209599982:GA:G	acceptor_gain	1.0000
1:209599982:GAGG:G	acceptor_gain	1.0000
1:209599982:GAGGA:G	acceptor_gain	1.0000
1:209600109:AAA:A	donor_gain	1.0000
1:209600110:AA:A	donor_gain	1.0000
1:209600111:AG:A	donor_loss	1.0000
1:209600112:G:GG	donor_gain	1.0000
1:209600113:T:G	donor_loss	1.0000
1:209600114:G:GT	donor_loss	1.0000
1:209603209:CCCA:C	acceptor_loss	1.0000

AlphaMissense

3139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:209595071:G:A	G30R	1.000
1:209595071:G:C	G30R	1.000
1:209595072:G:A	G30E	1.000
1:209599984:G:A	G32R	1.000
1:209599984:G:C	G32R	1.000
1:209599985:G:A	G32E	1.000
1:209599990:T:C	F34L	1.000
1:209599992:C:A	F34L	1.000
1:209599992:C:G	F34L	1.000
1:209599993:T:C	S35P	1.000
1:209600039:C:A	A50D	1.000
1:209600042:T:C	L51P	1.000
1:209600044:A:C	K52Q	1.000
1:209600044:A:G	K52E	1.000
1:209600045:A:T	K52M	1.000
1:209600046:G:C	K52N	1.000
1:209600046:G:T	K52N	1.000
1:209600093:A:G	E68G	1.000
1:209600093:A:T	E68V	1.000
1:209603276:T:C	L95P	1.000
1:209605553:T:C	L105P	1.000
1:209605562:G:C	R108P	1.000
1:209605597:G:C	A120P	1.000
1:209605598:C:A	A120D	1.000
1:209605640:T:C	L134P	1.000
1:209605658:T:A	V140D	1.000
1:209605660:C:G	H141D	1.000
1:209605661:A:G	H141R	1.000
1:209605664:G:C	R142T	1.000
1:209605664:G:T	R142I	1.000

dbSNP variants (sampled 300 via entrez): RS1000052757 (1:209593657 G>A,T), RS1000095736 (1:209593278 C>A,G), RS1000261132 (1:209588250 A>G), RS1000345097 (1:209598953 C>T), RS1000417898 (1:209582577 G>A,T), RS1000513774 (1:209609644 G>A), RS1000549546 (1:209593029 A>C,G,T), RS1000634507 (1:209588493 C>T), RS1000968788 (1:209604367 G>T), RS1001071172 (1:209609491 A>G), RS1001073247 (1:209582860 C>G), RS1001297106 (1:209600268 T>G), RS1001344946 (1:209588789 T>A,C), RS1001385707 (1:209588570 G>C), RS1001395190 (1:209610445 T>C)

Disease associations

OMIM: gene MIM:614994 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001240_1	Obesity (extreme)	2.000000e-06
GCST001981_1	Amyotrophic lateral sclerosis	3.000000e-08
GCST009443_1	Age-related cognitive decline (visuospatial skill) (slope of z-scores)	6.000000e-06
GCST010988_268	Adult body size	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5258 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 142,468 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL3544964	RAVOXERTINIB	2	1,243
CHEMBL475251	R-406	2	762
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CAMK1 family

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 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
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 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

40 potent at pChembl≥5 of 40 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	DOVITINIB
9.00	IC50	1	nM	CHEMBL4635883
8.40	IC50	3.96	nM	STAUROSPORINE
8.27	IC50	5.34	nM	STAUROSPORINE
8.13	IC50	7.41	nM	STAUROSPORINE
7.96	IC50	11	nM	CHEMBL4635883
7.64	Kd	23	nM	STAUROSPORINE
7.28	Kd	53	nM	STAUROSPORINE
7.26	IC50	55	nM	CHEMBL4635883
6.93	Kd	117	nM	RAVOXERTINIB
6.58	Kd	260	nM	NINTEDANIB
6.52	Kd	302	nM	CHEMBL4576489
6.49	Kd	326	nM	CHEMBL4465866
6.36	Kd	440	nM	SUNITINIB
6.34	Kd	460	nM	R-406
6.33	Kd	470	nM	LESTAURTINIB
6.03	Kd	940	nM	SU-014813
6.00	Kd	990	nM	SUNITINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.75	Kd	1800	nM	MIDOSTAURIN
5.68	Kd	2100	nM	KW-2449
5.66	Kd	2200	nM	RUXOLITINIB
5.52	IC50	3000	nM	CHEMBL4795714
5.52	Kd	3000	nM	TAE-684
5.50	Kd	3200	nM	FEDRATINIB
5.43	Kd	3700	nM	PAZOPANIB
5.38	Kd	4200	nM	CHEMBL2425628
5.38	Kd	4200	nM	SP-600125
5.32	IC50	4810	nM	CHEMBL579353
5.21	Kd	6200	nM	CHEMBL1908395
5.19	Kd	6500	nM	TOZASERTIB
5.17	Kd	6800	nM	PICTILISIB

PubChem BioAssay actives

34 with measured affinity, of 439 total; 24 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	1424927: 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	0.0010	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[[2,6-di(propan-2-yl)-4-pyridinyl]amino]pyrimidine-5-carboxamide	1668918: Inhibition of human CAMK1G using KKALRRQETVDAL as substrate in presence of [gamma-33P]-ATP by hotspot assay	ic50	0.0010	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	1715429: Inhibition of human CAMK1G using KKALRRQETVDAL as substrate by [gamma-33P]-ATP assay	ic50	0.0040	uM
1-[(1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl]-4-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]pyridin-2-one	1424927: 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	0.1170	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625119: Binding constant for CAMK1G kinase domain	kd	0.2600	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	1526248: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged CAMK1G (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr in presence of calmodulin by TR-FRET assay	kd	0.3020	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	1526248: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged CAMK1G (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr in presence of calmodulin by TR-FRET assay	kd	0.3260	uM
Sunitinib	435151: Binding constant for CAMK1G kinase domain	kd	0.4400	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625119: Binding constant for CAMK1G kinase domain	kd	0.4600	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	625119: Binding constant for CAMK1G kinase domain	kd	0.4700	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435151: Binding constant for CAMK1G kinase domain	kd	0.9400	uM
Midostaurin	435151: Binding constant for CAMK1G kinase domain	kd	1.8000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625119: Binding constant for CAMK1G kinase domain	kd	2.1000	uM
Ruxolitinib	625119: Binding constant for CAMK1G kinase domain	kd	2.2000	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	625119: Binding constant for CAMK1G kinase domain	kd	3.0000	uM
1-pentyl-4-(2-phenylmethoxyphenyl)imidazol-2-amine;hydrochloride	1734147: Inhibition of wild-type human CAMK1gamma using KKALRRQETVDAL peptide as substrate in presence of Ca2+ calmodulin and [gamma-33P]-ATP by radiometric hotspot kinase assay	ic50	3.0000	uM
Fedratinib	625119: Binding constant for CAMK1G kinase domain	kd	3.2000	uM
Pazopanib	435151: Binding constant for CAMK1G kinase domain	kd	3.7000	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769533: Binding affinity to CAMK1G (unknown origin)	kd	4.2000	uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one	256581: Average Binding Constant for CAMK1G; NA=Not Active at 10 uM	kd	4.2000	uM
4-N-[7-chloro-2-[(E)-2-(2-chloro-4,5-dimethoxyphenyl)ethenyl]quinazolin-4-yl]-1-N,1-N-diethylpentane-1,4-diamine	1612802: Inhibition of human CAMK1G using KKALRRQETVDAL as substrate by [gamma-33P]-ATP assay	ic50	4.8100	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625119: Binding constant for CAMK1G kinase domain	kd	6.2000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625119: Binding constant for CAMK1G kinase domain	kd	6.5000	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	625119: Binding constant for CAMK1G kinase domain	kd	6.8000	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
cobaltous chloride	decreases expression	1
zinc chromate	increases abundance, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Atrazine	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Vanadates	increases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases expression	1

ChEMBL screening assays

137 unique, capped per target: 136 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1034109	Binding	Inhibition of CAMK1G at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL5444395	Functional	Affinity Phenotypic Cellular interaction: (Western Blot assay (autophophorylation of CAMK1D in MDA-MB-231 cells) ) EUB0000878a CAMK1G	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Clinical trials (associated diseases)

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