CAMK2D

Summary

CAMK2D (calcium/calmodulin dependent protein kinase II delta, HGNC:1462) is a protein-coding gene on chromosome 4q26, encoding Calcium/calmodulin-dependent protein kinase type II subunit delta (Q13557). Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarc….

The product of this gene 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 delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.

Source: NCBI Gene 817 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 27
• Clinical variants (ClinVar): 86 total — 7 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 40 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001321571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1462
Approved symbol	CAMK2D
Name	calcium/calmodulin dependent protein kinase II delta
Location	4q26
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145349
Ensembl biotype	protein_coding
OMIM	607708
Entrez	817

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 53 protein_coding, 6 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000296402, ENST00000342666, ENST00000379773, ENST00000394522, ENST00000394524, ENST00000505132, ENST00000505990, ENST00000508738, ENST00000509594, ENST00000509907, ENST00000511664, ENST00000513132, ENST00000514328, ENST00000515496, ENST00000683023, ENST00000699047, ENST00000699048, ENST00000699372, ENST00000699373, ENST00000699374, ENST00000699375, ENST00000699376, ENST00000699377, ENST00000699378, ENST00000699379, ENST00000699380, ENST00000699381, ENST00000699382, ENST00000699415, ENST00000699416, ENST00000699417, ENST00000699418, ENST00000699419, ENST00000699420, ENST00000699421, ENST00000706055, ENST00000706056, ENST00000706057, ENST00000867798, ENST00000867799, ENST00000867800, ENST00000867801, ENST00000867802, ENST00000867803, ENST00000947047, ENST00000947048, ENST00000947049, ENST00000947050, ENST00000947051, ENST00000947052, ENST00000947053, ENST00000947054, ENST00000947055, ENST00000947056, ENST00000947057, ENST00000947058, ENST00000947059, ENST00000947060, ENST00000947061, ENST00000947062, ENST00000947063, ENST00000947064, ENST00000947065

RefSeq mRNA: 48 — MANE Select: NM_001321571 NM_001221, NM_001321566, NM_001321567, NM_001321568, NM_001321569, NM_001321570, NM_001321571, NM_001321572, NM_001321573, NM_001321574, NM_001321575, NM_001321576, NM_001321577, NM_001321578, NM_001321579, NM_001321580, NM_001321581, NM_001321582, NM_001321583, NM_001321584, NM_001321585, NM_001321586, NM_001321587, NM_001321588, NM_001321589, NM_001321590, NM_001321591, NM_001321592, NM_001396964, NM_001396965, NM_001396966, NM_001396967, NM_001399855, NM_001399856, NM_001399857, NM_001399858, NM_001399859, NM_001399860, NM_001399861, NM_001399862, NM_001399863, NM_001399864, NM_001399865, NM_172114, NM_172115, NM_172127, NM_172128, NM_172129

CCDS: CCDS3703, CCDS3704, CCDS43263, CCDS47127, CCDS54797, CCDS82948, CCDS82949, CCDS82950, CCDS93601, CCDS93602, CCDS93603, CCDS93604, CCDS93605, CCDS93606, CCDS93607, CCDS93608, CCDS93609, CCDS93610, CCDS93611, CCDS93612

Canonical transcript exons

ENST00000511664 — 21 exons

Exon	Start	End
ENSE00001003903	113500463	113500511
ENSE00001003911	113515069	113515191
ENSE00001003913	113552031	113552096
ENSE00001121155	113465529	113465604
ENSE00001121166	113509638	113509675
ENSE00001276264	113457335	113457563
ENSE00001276352	113609152	113609206
ENSE00001276388	113455726	113455821
ENSE00001617342	113537341	113537443
ENSE00001625946	113502936	113502977
ENSE00001716426	113504976	113505035
ENSE00001752494	113513328	113513370
ENSE00001791998	113513830	113513913
ENSE00002062068	113761004	113761738
ENSE00002459857	113517563	113517657
ENSE00002483543	113531216	113531299
ENSE00002496111	113661713	113661772
ENSE00002527351	113547644	113547716
ENSE00003519737	113759320	113759414
ENSE00003786791	113460147	113460241
ENSE00003994638	113451032	113454515

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.9422 / max 470.7728, expressed in 1753 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53684	35.0008	1733
53678	4.6475	1313
53679	3.6481	1263
53685	2.7767	1161
53676	2.0617	950
53677	0.8428	522
53681	0.8268	510
53682	0.5994	351
53686	0.3976	144
203317	0.3787	169

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.58	gold quality
myocardium	UBERON:0002349	99.37	gold quality
middle temporal gyrus	UBERON:0002771	99.31	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.29	gold quality
heart right ventricle	UBERON:0002080	99.07	gold quality
entorhinal cortex	UBERON:0002728	98.99	gold quality
tibialis anterior	UBERON:0001385	98.96	gold quality
deltoid	UBERON:0001476	98.80	gold quality
endothelial cell	CL:0000115	98.79	gold quality
pancreatic ductal cell	CL:0002079	98.65	gold quality
epithelial cell of pancreas	CL:0000083	98.56	gold quality
vastus lateralis	UBERON:0001379	98.21	gold quality
quadriceps femoris	UBERON:0001377	98.09	gold quality
biceps brachii	UBERON:0001507	97.95	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.66	gold quality
seminal vesicle	UBERON:0000998	97.63	gold quality
substantia nigra pars compacta	UBERON:0001965	97.63	gold quality
skeletal muscle tissue	UBERON:0001134	97.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.46	gold quality
ileal mucosa	UBERON:0000331	97.42	gold quality
cartilage tissue	UBERON:0002418	97.38	gold quality
superior frontal gyrus	UBERON:0002661	97.31	gold quality
muscle tissue	UBERON:0002385	96.98	gold quality
postcentral gyrus	UBERON:0002581	96.83	gold quality
cerebellar vermis	UBERON:0004720	96.80	gold quality
cardiac ventricle	UBERON:0002082	96.66	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11.19
E-MTAB-9801	yes	8.49
E-MTAB-6678	yes	8.04
E-MTAB-10042	yes	7.89
E-HCAD-30	no	564.15
E-CURD-112	no	2.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

153 targeting CAMK2D, 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-1277-5P	100.00	73.95	5056
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-145-5P	99.92	71.13	1836

Literature-anchored findings (GeneRIF, showing 29)

• role in cell communication (PMID:11889801)
• 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)
• HDAC4 as a specific downstream substrate of CaMKIIdeltaB in cardiac cells and have broad applications for the signaling pathways leading to cardiac hypertrophy and heart failure. (PMID:17179159)
• Chronic upregulation/activation of CaMKIID, and PKD in heart failure shifts HDAC5 out of the nucleus, derepressing transcription of hypertrophic genes. (PMID:18218981)
• The cloned, expressed CAMK2delta6 protein comigrated with D52 kinase and colocalized with D52 protein in T84 and HEK293 cells. These findings support a role for CAMK2delta6 in the mediation of D52 phosphorylation. (PMID:18832449)
• Calcium/Calmodulin-dependent protein kinase II delta 6 (CaMKIIdelta6) and RhoA is involved in thrombin-induced endothelial barrier dysfunction (PMID:20442409)
• The crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, is described. (PMID:20668654)
• This study shows for the first time that CAMKII inhibition acutely improves contractility in human heart failure where CAMKIIdelta expression is increased. (PMID:20814023)
• Single nucleotide polymorphism in CAMK2D gene is associated with epithelial ovarian cancer. (PMID:21447778)
• Data show that Pcp4 overexpression induces precocious neuronal differentiation, and is associated with an increase in CaMKIIdelta activation. (PMID:21491429)
• suggest that CaMKII and calcineurin provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization (PMID:22270398)
• End-stage failing human hearts had more phosphorylation at CaMKII-dependent titin sites, contributing to their mechanical dysfunction & establishing a new role for CaMKIIdelta in regulating diastolic passive properties of healthy & diseased hearts. (PMID:23283722)
• Our studies suggest that CaMKII is a molecular signal that couples increased reactive oxygen species with atrial fibrillation and that therapeutic strategies to decrease oxidized CaMKII may prevent or reduce it. (PMID:24030498)
• CAMKIIdelta is required for PP1gamma-exacerbated apoptosis of cardiomyocytes. (PMID:24196533)
• CaMKIID specifically phosphorylates Thr-457 on CEACAM1-SF, which in turn regulates the process of lumen formation via apoptosis of the central acinar cells. (PMID:24302721)
• This study showed that AKAP12,CAMK2D and a molecular pathway(cyclic amp)association to outcome of depressive during citalopram treatment. (PMID:24986638)
• Study found a significant association with disordered gambling and rs167771 (DRD3) and with rs381572 (CAMK2D) in humans (PMID:25266122)
• Reveal a novel in vivo function of CaMKIIdelta in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIdelta controls cardiac hypertrophy. (PMID:25421395)
• CaMKIId activity is up-regulated in the myocardium of diabetic patients and mouse models of diabetes, where it promotes pathological signaling that includes hypertrophy, fibrosis and apoptosis. (PMID:26198034)
• CEACAM1 is able to maintain the active transcription of ID4 by an epigenetic mechanism involving HDAC4 and CaMK2D, and the same kinase enables lumen formation by CEACAM1 (PMID:27302061)
• CKIalpha-mediated NS5A S235 phosphorylation is critical for HCV replication. CaMKII gamma and delta may have negative roles in the HCV life cycle. (PMID:27875595)
• TGFbeta elevated the expression of CamK IIbeta and CamK IIdelta, while siRNA silencing of those two subtypes significantly reduced TGFbeta-mediated expression of collagen A1 and fibronectin 1. (PMID:28130256)
• JNK2 activation up-regulates CaMKIIdelta expression in the aged atrium and may promote the occurrence of cardiac arrhythmias. (PMID:29360953)
• This study provides new evidence supporting direct interaction between CaMKIIdelta and IKKbeta in pro-inflammatory signalling in cardiac fibroblasts and could represent a feature that may be exploited for therapeutic benefit. (PMID:30059730)
• Sphingosine kinase 1 regulates HMGB1 translocation by directly interacting with calcium/calmodulin protein kinase II-delta in sepsis-associated liver injury. (PMID:33281190)
• miR-145-5p affects autophagy by targeting CaMKIIdelta in atherosclerosis. (PMID:35597494)
• TRPM1 promotes tumor progression in acral melanoma by activating the Ca[2+]/CaMKIIdelta/AKT pathway. (PMID:36585114)
• CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma. (PMID:37468549)
• Role of CAMK2D in neurodevelopment and associated conditions. (PMID:38272033)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	camk2d1	ENSDARG00000043010

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), 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 II subunit delta — Q13557 (reviewed: Q13557)

All UniProt accessions (23): A0A8V8TN60, A0A8V8TN65, A0A8V8TN88, A0A8V8TNA1, A0A8V8TNA7, A0A8V8TND4, A0A8V8TNN4, A0A8V8TNN9, A0A8V8TNR6, A0A8V8TPJ8, A0A8V8TPK3, Q13557, A0A8V8TPM4, A0A8V8TPY4, A0A8V8TQ10, A0A994J516, A0A994J5B0, A0A994J7X8, D6R938, E9PBG7, E9PF82, H0Y9C2, H0Y9J2

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on ‘Ser-2808’. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. 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. Interacts with RRAD and CACNB2.

Subcellular location. Cell membrane. Sarcolemma. Sarcoplasmic reticulum membrane.

Tissue specificity. Expressed in cardiac muscle and skeletal muscle. Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9 are expressed in cardiac muscle. Isoform Delta 11 is 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.

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.

Miscellaneous. Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in PubMed:10189359.

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

Isoforms (10)

UniProt ID	Names	Canonical?
Q13557-1	Delta 2	yes
Q13557-3	Delta 3
Q13557-4	Delta 4
Q13557-8	Delta 6
Q13557-9	Delta 7
Q13557-5	Delta 8
Q13557-6	Delta 9
Q13557-10	Delta 10
Q13557-11	Delta 11
Q13557-12	Delta 12

RefSeq proteins (47): NP_001212, NP_001308495, NP_001308496, NP_001308497, NP_001308498, NP_001308499, NP_001308500, NP_001308501, NP_001308502, NP_001308503, NP_001308504, NP_001308505, NP_001308506, NP_001308507, NP_001308508, NP_001308509, NP_001308510, NP_001308511, NP_001308512, NP_001308513, NP_001308514, NP_001308515, NP_001308516, NP_001308517, NP_001308518, NP_001308519, NP_001308520, NP_001383893, NP_001383894, NP_001383895, NP_001383896, NP_001386784, NP_001386785, NP_001386786, NP_001386787, NP_001386788, NP_001386789, NP_001386790, NP_001386791, NP_001386792, NP_001386793, NP_001386794, NP_742112, NP_742113, NP_742125, NP_742126, NP_742127 (=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 (71 total): helix 20, modified residue 15, strand 13, splice variant 6, turn 4, sequence variant 3, region of interest 2, sequence conflict 2, binding site 2, initiator methionine 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3GP2	X-RAY DIFFRACTION	1.46
7ZRQ	X-RAY DIFFRACTION	1.68
2WEL	X-RAY DIFFRACTION	1.9
5VLO	X-RAY DIFFRACTION	2.05
6AYW	X-RAY DIFFRACTION	2.05
2VN9	X-RAY DIFFRACTION	2.3
9BLH	X-RAY DIFFRACTION	2.35
7ZRP	X-RAY DIFFRACTION	2.65
2W2C	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13557-F1	84.10	0.60

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): 20–28; 43

Post-translational modifications (15): 306, 307, 315, 318, 319, 330, 331, 333, 336, 337, 404, 490, 494, 2, 287

Function

Pathways and Gene Ontology

Reactome pathways

60 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-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
R-HSA-112316	Neuronal System

MSigDB gene sets: 497 (showing top): ATF_B, AHRARNT_01, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_RELAXATION_OF_CARDIAC_MUSCLE, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION, ACTGCAG_MIR173P, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY

GO Biological Process (27): regulation of cell growth (GO:0001558), regulation of the force of heart contraction (GO:0002026), regulation of membrane depolarization (GO:0003254), regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468), regulation of heart contraction (GO:0008016), positive regulation of cardiac muscle hypertrophy (GO:0010613), regulation of cell communication by electrical coupling (GO:0010649), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), endoplasmic reticulum calcium ion homeostasis (GO:0032469), regulation of neuronal synaptic plasticity (GO:0048168), relaxation of cardiac muscle (GO:0055119), long-term synaptic potentiation (GO:0060291), regulation of ryanodine-sensitive calcium-release channel activity (GO:0060314), regulation of cellular localization (GO:0060341), cellular response to calcium ion (GO:0071277), cardiac muscle cell contraction (GO:0086003), regulation of heart rate by cardiac conduction (GO:0086091), regulation of cardiac muscle cell action potential (GO:0098901), regulation of cardiac muscle cell action potential involved in regulation of contraction (GO:0098909), regulation of cell communication by electrical coupling involved in cardiac conduction (GO:1901844), regulation of relaxation of cardiac muscle (GO:1901897), negative regulation of sodium ion transmembrane transport (GO:1902306), regulation of calcium ion transmembrane transport via high voltage-gated calcium channel (GO:1902514), regulation of protein localization to plasma membrane (GO:1903076)

GO Molecular Function (15): protein serine/threonine kinase activity (GO:0004674), calcium/calmodulin-dependent protein kinase activity (GO:0004683), calmodulin binding (GO:0005516), ATP binding (GO:0005524), sodium channel inhibitor activity (GO:0019871), titin binding (GO:0031432), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), transmembrane transporter binding (GO:0044325), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (13): nucleus (GO:0005634), 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), sarcolemma (GO:0042383), neuron projection (GO:0043005), plasma membrane (GO:0005886), sarcoplasmic reticulum (GO:0016529)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Oncogenic MAPK signaling	4
Activation of NMDA receptors and postsynaptic events	3
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
Post NMDA receptor activation events	1
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
regulation of cellular process	2
regulation of release of sequestered calcium ion into cytosol	2
endoplasmic reticulum	2
regulation of synaptic plasticity	2
protein kinase activity	2
bounding membrane of organelle	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
regulation of heart contraction	1
regulation of biological quality	1
regulation of membrane potential	1
membrane depolarization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
phosphorylation	1
protein modification process	1
heart contraction	1
regulation of blood circulation	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
cell communication by electrical coupling	1
regulation of cell communication	1
cardiac muscle cell apoptotic process	1
positive regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
intracellular calcium ion homeostasis	1
relaxation of muscle	1
positive regulation of synaptic transmission	1
ryanodine-sensitive calcium-release channel activity	1
regulation of transmembrane transporter activity	1
regulation of localization	1
cellular localization	1
response to calcium ion	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMK2D	ADRB1	P08588	764
CAMK2D	RYR2	Q92736	725
CAMK2D	CAMK2A	Q9UQM7	647
CAMK2D	CALM1	P02593	642
CAMK2D	CALML3	P27482	610
CAMK2D	CALML5	Q9NZT1	608
CAMK2D	RBM20	Q5T481	592
CAMK2D	CALML4	Q96GE6	589
CAMK2D	CALML6	Q8TD86	582
CAMK2D	ADCY8	P40145	563
CAMK2D	SRSF1	Q07955	562
CAMK2D	PHACTR4	Q8IZ21	522
CAMK2D	GRM3	Q14832	512
CAMK2D	GRIN2A	Q12879	505
CAMK2D	SSH2	Q76I76	486

IntAct

208 interactions, top by confidence:

A	B	Type	Score
ACBD6	NMT2	psi-mi:“MI:0914”(association)	0.870
CAMK2A	CAMK2D	psi-mi:“MI:0407”(direct interaction)	0.860
MCM5	MCM3	psi-mi:“MI:0914”(association)	0.850
RIN1	NRAS	psi-mi:“MI:0914”(association)	0.840
CAMK2B	CAMK2D	psi-mi:“MI:0407”(direct interaction)	0.820
CAMK2B	CAMK2D	psi-mi:“MI:0915”(physical association)	0.820
CAMK2G	CAMK2D	psi-mi:“MI:0407”(direct interaction)	0.810
CAMK2G	CAMK2D	psi-mi:“MI:0914”(association)	0.810
CAMK2D	DNAL4	psi-mi:“MI:0915”(physical association)	0.740
DNAL4	CAMK2D	psi-mi:“MI:0915”(physical association)	0.740
CAMK2D	CAMK2D	psi-mi:“MI:0915”(physical association)	0.740
CAMK2D	CAMK2D	psi-mi:“MI:0407”(direct interaction)	0.740
CAMK2A	CAMK2G	psi-mi:“MI:0914”(association)	0.730
CALM1	CAMK2D	psi-mi:“MI:0915”(physical association)	0.730
CAMK2D	CALM1	psi-mi:“MI:0407”(direct interaction)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
TNPO2	CAMK2D	psi-mi:“MI:0915”(physical association)	0.670
CAMK2D	TTC5	psi-mi:“MI:0915”(physical association)	0.670
CAMK2D	BANP	psi-mi:“MI:0915”(physical association)	0.670
MRPL11	CAMK2D	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (293): CAMK2D (Two-hybrid), FKBP1B (Two-hybrid), FXR2 (Two-hybrid), DNAL4 (Two-hybrid), TNPO2 (Two-hybrid), BANP (Two-hybrid), MOAP1 (Two-hybrid), FNDC3B (Two-hybrid), MRPL11 (Two-hybrid), TTC5 (Two-hybrid), EPHA10 (Two-hybrid), CAMK2D (Affinity Capture-MS), CAMK2D (Biochemical Activity), CAMK2D (Affinity Capture-MS), CAMK2D (Affinity Capture-MS)

ESM2 similar proteins: A0A087WV53, A1CS92, A2ABU4, A2Q908, A2RUH7, A4QZL9, D3ZHA0, O01761, O70468, O75369, O88599, P05548, P11275, P11730, P11798, P13466, P21333, P56276, P56741, P70402, P79280, Q05623, Q13177, Q13203, Q13557, Q14315, Q2GM53, Q2HJF7, Q2URB7, Q5FW53, Q5PQM4, Q5RCC4, Q5VTT5, Q5ZJJ9, Q5ZKI0, Q62422, Q63518, Q6C1H8, Q6P686, Q6PHZ2

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

24 interactions.

A	Effect	B	Mechanism
CAMK2D	up-regulates	HDAC4	phosphorylation
CAMK2D	unknown	TPD52	phosphorylation
CAMK2D	up-regulates	CACNB2	phosphorylation
CAMK2D	down-regulates	SCN5A	phosphorylation
CAMK2D	down-regulates	KCNJ11	phosphorylation
CAMK2D	up-regulates	CEACAM1	phosphorylation
calcium(2+)	“up-regulates activity”	CAMK2D	“chemical activation”
CAMK2D	up-regulates	CAMK2D	phosphorylation
CAMK2D	up-regulates	Myoblast_fusion
CAMK2D	up-regulates	MEF2A
CAMK2D	“up-regulates activity”	SCN5A	phosphorylation
CAMK2D	“up-regulates activity”	SCN8A	phosphorylation
CAMK2D	unknown	VIM	phosphorylation
CAMK2D	“down-regulates activity”	ITPR2	phosphorylation
CAMK2D	“down-regulates activity”	ANKRD28	phosphorylation
CAMK2D	“down-regulates activity”	KCNQ1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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
Ras activation upon Ca2+ influx through NMDA receptor	5	23.0×	4e-04
Cellular response to heat stress	6	19.1×	4e-04
Signaling by RAS mutants	5	17.1×	6e-04
Phase 0 - rapid depolarisation	6	16.7×	4e-04
Transcriptional Regulation by MECP2	6	15.3×	4e-04
Regulation of MECP2 expression and activity	5	14.8×	1e-03
RAF activation	5	13.5×	1e-03
Signaling by RAF1 mutants	6	13.5×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
detection of calcium ion	5	36.7×	8e-05
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	6	26.4×	5e-05
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	5	22.0×	7e-04
regulation of heart rate	5	15.3×	2e-03
regulation of cytokinesis	5	13.8×	3e-03
G2/M transition of mitotic cell cycle	6	12.2×	2e-03
substantia nigra development	5	12.0×	6e-03
long-term synaptic potentiation	6	11.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	49
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1343374	NM_001321571.2(CAMK2D):c.275+1G>T	Pathogenic
1343375	NM_001321571.2(CAMK2D):c.236G>A (p.Ser79Asn)	Pathogenic
1343376	NM_001321571.2(CAMK2D):c.416C>T (p.Pro139Leu)	Pathogenic
1343377	NM_001321571.2(CAMK2D):c.821A>C (p.Gln274Pro)	Pathogenic
1343378	NM_001321571.2(CAMK2D):c.824G>A (p.Arg275His)	Pathogenic
1343379	NM_001321571.2(CAMK2D):c.873G>C (p.Leu291Phe)	Pathogenic
2442394	NM_001321571.2(CAMK2D):c.628G>A (p.Gly210Arg)	Pathogenic
1343380	NM_001321571.2(CAMK2D):c.881T>C (p.Phe294Ser)	Likely pathogenic
4531923	NM_001321571.2(CAMK2D):c.328G>A (p.Glu110Lys)	Likely pathogenic

SpliceAI

5080 predictions. Top by Δscore:

Variant	Effect	Δscore
4:113457333:A:AC	donor_gain	1.0000
4:113457334:C:CC	donor_gain	1.0000
4:113457388:T:A	donor_gain	1.0000
4:113457559:CAAAG:C	acceptor_gain	1.0000
4:113460237:TTTTT:T	acceptor_gain	1.0000
4:113460239:TTT:T	acceptor_gain	1.0000
4:113460240:TT:T	acceptor_gain	1.0000
4:113460242:C:CC	acceptor_gain	1.0000
4:113465521:CTACT:C	donor_loss	1.0000
4:113465522:TAC:T	donor_loss	1.0000
4:113465523:AC:A	donor_loss	1.0000
4:113465527:A:AC	donor_gain	1.0000
4:113465527:AC:A	donor_loss	1.0000
4:113465528:C:CA	donor_gain	1.0000
4:113465600:TCGTG:T	acceptor_gain	1.0000
4:113465601:CGTG:C	acceptor_gain	1.0000
4:113465601:CGTGC:C	acceptor_gain	1.0000
4:113465602:GTG:G	acceptor_gain	1.0000
4:113465603:TG:T	acceptor_gain	1.0000
4:113465603:TGC:T	acceptor_loss	1.0000
4:113465604:GCTAA:G	acceptor_loss	1.0000
4:113465605:C:CC	acceptor_gain	1.0000
4:113465605:C:T	acceptor_loss	1.0000
4:113465606:T:G	acceptor_loss	1.0000
4:113508280:A:T	acceptor_gain	1.0000
4:113509636:A:AC	donor_gain	1.0000
4:113509636:ACCT:A	donor_loss	1.0000
4:113509637:C:CC	donor_gain	1.0000
4:113509672:GCTG:G	acceptor_loss	1.0000
4:113509673:CTG:C	acceptor_gain	1.0000

AlphaMissense

3521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:113457384:A:G	W462R	1.000
4:113457384:A:T	W462R	1.000
4:113457405:A:G	W455R	1.000
4:113457405:A:T	W455R	1.000
4:113457410:C:G	R453P	1.000
4:113457467:A:G	L434P	1.000
4:113465560:C:G	A360P	1.000
4:113465568:A:G	L357P	1.000
4:113513834:A:G	L300P	1.000
4:113513839:T:A	R298S	1.000
4:113513839:T:G	R298S	1.000
4:113513840:C:G	R298T	1.000
4:113513851:A:C	F294L	1.000
4:113513851:A:T	F294L	1.000
4:113513852:A:G	F294S	1.000
4:113513853:A:G	F294L	1.000
4:113513861:A:G	L291S	1.000
4:113515075:C:A	W271C	1.000
4:113515075:C:G	W271C	1.000
4:113515077:A:G	W271R	1.000
4:113515077:A:T	W271R	1.000
4:113515110:G:T	R260S	1.000
4:113515130:A:G	L253P	1.000
4:113515130:A:T	L253H	1.000
4:113515133:A:C	M252R	1.000
4:113515142:A:T	I249N	1.000
4:113515145:A:G	L248P	1.000
4:113515150:T:A	K246N	1.000
4:113515150:T:G	K246N	1.000
4:113515154:G:T	A245D	1.000

dbSNP variants (sampled 300 via entrez): RS10000007 (4:113632097 A>C,T), RS1000003392 (4:113516864 T>A), RS1000004353 (4:113495374 C>A), RS1000008172 (4:113588702 A>G), RS1000020241 (4:113492145 G>A,T), RS1000030133 (4:113492376 T>A,G), RS1000040541 (4:113762864 A>G), RS1000055666 (4:113656345 C>T), RS1000058188 (4:113495645 C>T), RS1000061297 (4:113581923 A>C,G), RS10000775 (4:113625533 C>A,T), RS1000081374 (4:113750135 G>A), RS1000087517 (4:113661183 C>T), RS1000096597 (4:113613505 G>A), RS1000108882 (4:113536557 AAGTC>A)

Disease associations

OMIM: gene MIM:607708 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal dominant
CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy	Strong	AD

Mondo (3): neurodevelopmental disorder (MONDO:0700092), CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy (MONDO:1040008), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST001764_3	White matter integrity (bipolar disorder risk interaction)	4.000000e-06
GCST002299_2	Chronic lymphocytic leukemia	3.000000e-09
GCST002577_1	Non-small cell lung cancer (survival)	3.000000e-07
GCST004146_33	Chronic lymphocytic leukemia	6.000000e-10
GCST004826_6	P wave duration	4.000000e-08
GCST004902_21	Parkinson’s disease	5.000000e-11
GCST006061_91	Atrial fibrillation	9.000000e-09
GCST006061_92	Atrial fibrillation	2.000000e-09
GCST006414_87	Atrial fibrillation	2.000000e-13
GCST007045_26	PR interval	3.000000e-09
GCST007576_173	Chronotype	4.000000e-09
GCST008156_31	Hip circumference adjusted for BMI	5.000000e-07
GCST009017_5	T wave morphology restitution during recovery from exercise (MTAG)	2.000000e-07
GCST009069_5	T wave morphology restitution during recovery from exercise	3.000000e-08
GCST009325_82	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-12
GCST010154_1	Small vessel stroke (CCS and TOAST classification)	1.000000e-08
GCST010321_134	PR interval	2.000000e-25
GCST010346_37	TPE interval (resting)	3.000000e-10
GCST010796_1787	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-18
GCST010796_1788	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-21
GCST010796_1789	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST010796_1790	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010796_1791	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_1792	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1793	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-24
GCST011010_19	Electrocardiographic traits (multivariate)	6.000000e-09
GCST012490_522	Femur bone mineral density x serum urate levels interaction	8.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004641	white matter integrity
EFO:0000714	survival time
EFO:0005094	P wave duration
EFO:0004462	PR interval
EFO:0008328	chronotype measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0008398	T wave morphology measurement
EFO:1001504	small vessel stroke
EFO:0004644	TPE interval measurement
EFO:0004327	electrocardiography
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2097164 (PROTEIN FAMILY), CHEMBL2801 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

40 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 428,016 (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
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
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
CHEMBL553	ERLOTINIB	4	108,300
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
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

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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 15b [PMID: 18334293]	Inhibition	8.05	pIC50
compound 27 [PMID: 18337095]	Inhibition	8.0	pIC50
MELK-TI	Inhibition	6.09	pIC50

Binding affinities (BindingDB)

382 measured of 382 human assays (382 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-amino-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.04 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
[(2R)-2-(aminomethyl)piperidin-1-yl]-[2-chloro-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)-4-pyridinyl]methanone	IC50	0.05 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(methylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.05 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-[(3R)-3-aminopyrrolidin-1-yl]-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.05 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(1H-pyrazol-4-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.05 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(1H-pyrazol-4-ylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.06 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[(2S)-2-(hydroxymethyl)azetidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.06 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[(3R)-3-hydroxypyrrolidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.06 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[2-(dimethylamino)ethylamino]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.07 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-(3-carbamoylazetidin-1-yl)-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.07 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-methoxy-3-methylazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.07 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(2-sulfamoylethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.07 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[(3S)-3-hydroxypyrrolidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.07 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-[(3S)-3-aminopyrrolidin-1-yl]-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.07 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(2-methoxyethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.08 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(1-methylpyrazol-4-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.08 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.09 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[3-(methanesulfonamido)azetidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.09 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-methoxyazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-(3-cyanoazetidin-1-yl)-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-hydroxyazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[3-(methylamino)azetidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[3-(dimethylamino)azetidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[3-(hydroxymethyl)azetidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-hydroxy-3-methylazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(2-hydroxyethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(1H-pyrazol-5-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[2-(dimethylamino)ethoxy]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(2-hydroxy-2-methylpropoxy)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.1 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(ethylcarbamoylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.11 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[[(2S)-2-hydroxypropyl]amino]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.11 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-hydroxypropylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.11 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-fluoroazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.13 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-methoxyazetidin-1-yl)-6-(5-thiophen-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.13 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[(3-hydroxy-3-methylbutyl)amino]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.13 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(1H-imidazol-2-ylmethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.13 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[1-(oxetan-3-yl)pyrazol-4-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.13 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-methoxy-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-methylsulfonylazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[[(2R)-2-hydroxypropyl]amino]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(2-morpholin-4-ylethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(3-oxopiperazin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.14 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-(3-acetamidoazetidin-1-yl)-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.15 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-[1-(2-cyanoethyl)pyrazol-4-yl]-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.15 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[5-(5-fluorothiophen-2-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-6-[(2S)-2-(methylcarbamoyl)azetidin-1-yl]pyridine-4-carboxamide	IC50	0.15 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-(1,1-dioxo-1,2-thiazolidin-2-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.16 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
N-[(2S)-2-(diethylamino)propyl]-2-[3-(ethylsulfonylamino)azetidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.16 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors
2-(cyclopropanecarbonylamino)-N-[(2S)-2-(diethylamino)propyl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	IC50	0.16 nM	US-10100058: Fused heterocyclic compounds as CaM kinase inhibitors

ChEMBL bioactivities

511 potent at pChembl≥5 of 525 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.51	IC50	0.0311	nM	STAUROSPORINE
10.43	IC50	0.0372	nM	STAUROSPORINE
10.30	IC50	0.05	nM	CHEMBL4218769
10.22	IC50	0.06	nM	CHEMBL4208018
10.19	IC50	0.0645	nM	STAUROSPORINE
10.15	IC50	0.07	nM	CHEMBL4215817
10.10	IC50	0.08	nM	CHEMBL4218245
10.05	IC50	0.09	nM	CHEMBL4217261
10.00	IC50	0.1	nM	CHEMBL4206514
10.00	IC50	0.1	nM	CHEMBL4215300
10.00	IC50	0.1	nM	CHEMBL4210359
9.66	IC50	0.22	nM	CHEMBL4209816
9.64	IC50	0.23	nM	CHEMBL4213838
9.55	IC50	0.28	nM	CHEMBL4210881
9.52	IC50	0.3	nM	CHEMBL4205997
9.49	Kd	0.32	nM	STAUROSPORINE
9.30	Kd	0.5	nM	STAUROSPORINE
9.04	IC50	0.92	nM	CHEMBL4209443
8.80	IC50	1.6	nM	CHEMBL4205708
8.70	IC50	2	nM	CHEMBL3699625
8.70	IC50	2	nM	CHEMBL3216550
8.70	IC50	2	nM	STAUROSPORINE
8.66	IC50	2.17	nM	CHEMBL4211430
8.59	IC50	2.6	nM	ABEMACICLIB
8.48	IC50	3.3	nM	CHEMBL4213305
8.47	IC50	3.4	nM	CHEMBL4209840
8.46	IC50	3.5	nM	CHEMBL4210568
8.40	IC50	4	nM	CHEMBL4208717
8.40	Kd	4	nM	CHEMBL4465866
8.40	IC50	4	nM	STAUROSPORINE
8.40	Ki	3.981	nM	TAE-684
8.30	Ki	5.012	nM	CHEMBL1998159
8.24	IC50	5.8	nM	CHEMBL4216080
8.22	Kd	6	nM	CHEMBL4576489
8.22	IC50	6	nM	STAUROSPORINE
8.14	IC50	7.2	nM	CHEMBL4213540
8.11	Kd	7.861	nM	CHEMBL5653589
8.10	IC50	8	nM	CHEMBL3699629
8.06	Kd	8.8	nM	LESTAURTINIB
8.05	IC50	9	nM	CHEMBL270849
8.04	IC50	9.1	nM	CHEMBL4214345
8.00	IC50	10	nM	CHEMBL255607
8.00	Ki	10	nM	CHEMBL2002726
7.92	IC50	12	nM	CHEMBL272978
7.90	Ki	12.59	nM	CHEMBL1991063
7.89	IC50	13	nM	CHEMBL402340
7.80	Ki	15.85	nM	CHEMBL1970903
7.80	Ki	15.85	nM	CHEMBL2001751
7.77	IC50	17	nM	CHEMBL3699624
7.72	Kd	19	nM	ABEMACICLIB

PubChem BioAssay actives

244 with measured affinity, of 2120 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	1531610: Inhibition of human CAMK2D using KKLNRTLSFAEPG as substrate by [gamma-33P]-ATP assay	ic50	<0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(2-hydroxyethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(3-methoxyazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-[(3S)-3-hydroxypyrrolidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(2-methoxyethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(methylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-[(3R)-3-hydroxypyrrolidin-1-yl]-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(3-hydroxyazetidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0001	uM
N-[(2S)-2-(diethylamino)propyl]-2-(4-hydroxypiperidin-1-yl)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0002	uM
N-[(2S)-2-(diethylamino)propyl]-2-(dimethylamino)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0002	uM
N-[(2S)-2-(diethylamino)propyl]-2-morpholin-4-yl-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0003	uM
N-[(2S)-2-(diethylamino)propyl]-2-(2-methoxyethoxy)-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0003	uM
N-[(2S)-2-(diethylamino)propyl]-2-ethyl-6-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0009	uM
N-[2-(diethylamino)ethyl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0016	uM
6-chloro-2-N-(3,4-dichlorophenyl)-4-N-[2-(1-methylpyrrolidin-2-yl)ethyl]quinazoline-2,4-diamine;pentahydrochloride	641584: Inhibition of human recombinant CAMK2delta using tetramethylbenzidine as substrate by spectrophotometry analysis	ic50	0.0020	uM
N-[(2S)-1-(diethylamino)propan-2-yl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0022	uM
Abemaciclib	2199002: Inhibition of human CAMK2delta preincubated with compound for 20 mins followed by [33P]ATP addition and measured after 2 hrs by filter binding method	ic50	0.0026	uM
N-[2-(diethylamino)ethyl]-8-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)imidazo[1,2-a]pyridine-6-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0033	uM
N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0034	uM
N-[2-(diethylamino)ethyl]-3-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)benzamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0035	uM
N-[2-(diethylamino)ethyl]-3-methyl-7-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)benzimidazole-5-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0040	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	1526180: Binding affinity to recombinant human full-length N-terminal GST-tagged CAMK2D expressed in baculovirus expression system using GS peptide as substrate incubated for 1 hr by TR-FRET assay	kd	0.0040	uM
N-[2-(diethylamino)ethyl]-3-(6-thiophen-2-ylimidazo[1,2-b]pyridazin-3-yl)benzamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0058	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	1526180: Binding affinity to recombinant human full-length N-terminal GST-tagged CAMK2D expressed in baculovirus expression system using GS peptide as substrate incubated for 1 hr by TR-FRET assay	kd	0.0060	uM
N-[(2R)-2-(diethylamino)propyl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0072	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147984: Binding affinity to human CAMK2D incubated for 45 mins by Kinobead based pull down assay	kd	0.0079	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	507857: Binding affinity to CAMK2D	kd	0.0088	uM
N-(3-chlorophenyl)-4-(3-piperazin-1-ylphenyl)pyrimidin-2-amine	322069: Inhibition of cloned CaMK2delta	ic50	0.0090	uM
N-[3-(diethylamino)propyl]-2-(5-thiophen-2-ylpyrazolo[1,5-a]pyrimidin-3-yl)pyridine-4-carboxamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0091	uM
3-[3-(2-aminoethyl)indol-1-yl]-4-(5-chloro-1H-indol-3-yl)pyrrole-2,5-dione	322228: Inhibition of CaMK2delta	ic50	0.0100	uM
N’-[3-[2-(3-chloroanilino)pyrimidin-4-yl]phenyl]ethane-1,2-diamine	322069: Inhibition of cloned CaMK2delta	ic50	0.0120	uM
3-(5-chloro-1H-indol-3-yl)-4-[3-[2-(methylamino)ethyl]indol-1-yl]pyrrole-2,5-dione	322228: Inhibition of CaMK2delta	ic50	0.0130	uM
methyl 3-[4-[3-[2-(methylamino)ethyl]indol-1-yl]-2,5-dioxopyrrol-3-yl]-1H-indole-5-carboxylate	322228: Inhibition of CaMK2delta	ic50	0.0210	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147984: Binding affinity to human CAMK2D incubated for 45 mins by Kinobead based pull down assay	kd	0.0224	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
Brigatinib	2182812: Inhibition of human CAMK2D using KKLNRTLSFAEPG as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0290	uM
3-[3-(2-aminoethyl)indol-1-yl]-4-[5-(trifluoromethyl)-1H-indol-3-yl]pyrrole-2,5-dione	322228: Inhibition of CaMK2delta	ic50	0.0320	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
3-[1-(3-aminopropyl)indol-3-yl]-4-(5-bromo-1H-indol-3-yl)pyrrole-2,5-dione	322072: Inhibition of CaMK2delta	ic50	0.0340	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
Midostaurin	435647: Binding constant for CAMK2D kinase domain	kd	0.0360	uM
N-[2-(dimethylamino)ethyl]-3-(6-thiophen-2-ylimidazo[1,2-b]pyridazin-3-yl)benzamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0370	uM
3-[3-(2-aminoethyl)indol-1-yl]-4-(5-fluoro-1H-indol-3-yl)pyrrole-2,5-dione	322228: Inhibition of CaMK2delta	ic50	0.0380	uM
3-[1-(3-aminopropyl)indol-3-yl]-4-(1-benzothiophen-3-yl)pyrrole-2,5-dione	322227: Inhibition of CaMK2delta using 3 weeks old stock solution of compound	ic50	0.0390	uM
N-[2-[di(propan-2-yl)amino]ethyl]-3-(6-thiophen-2-ylimidazo[1,2-b]pyridazin-3-yl)benzamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0410	uM
4-[2-(3-chloroanilino)pyrimidin-4-yl]benzoic acid	322069: Inhibition of cloned CaMK2delta	ic50	0.0420	uM
N-[2-(diethylamino)ethyl]-3-(6-phenylimidazo[1,2-b]pyridazin-3-yl)benzamide	1370175: Inhibition of recombinant human full length His-tagged CaMK2delta expressed in baculovirus using Biotin labelled STK1 as substrate after 1 hr in presence of ATP by fluorescence assay	ic50	0.0440	uM
3-[4-[3-(2-aminoethyl)indol-1-yl]-2,5-dioxopyrrol-3-yl]-1H-indole-5-carbonitrile	322228: Inhibition of CaMK2delta	ic50	0.0460	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	4
Benzo(a)pyrene	decreases expression	4
bisphenol A	decreases expression, affects cotreatment, increases methylation	3
mercuric bromide	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
eprenetapopt	affects expression	1
bisphenol S	increases expression	1

ChEMBL screening assays

338 unique, capped per target: 337 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
CHEMBL1963738	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CAMK2D	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TD	Abcam HEK293T CAMK2D KO	Transformed cell line	Female
CVCL_D7LK	Ubigene A-549 CAMK2D KO	Cancer cell line	Male
CVCL_D8IB	Ubigene HCT 116 CAMK2D KO	Cancer cell line	Male
CVCL_D9AV	Ubigene HEK293 CAMK2D KO	Transformed cell line	Female
CVCL_D9Z8	Ubigene HeLa CAMK2D KO	Cancer cell line	Female
CVCL_SG66	HAP1 CAMK2D (-)	Cancer cell line	Male

Clinical trials (associated diseases)

204 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,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism