CAMK1D

Summary

CAMK1D (calcium/calmodulin dependent protein kinase ID, HGNC:19341) is a protein-coding gene on chromosome 10p13, encoding Calcium/calmodulin-dependent protein kinase type 1D (Q8IU85). Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendri….

This gene is a member of the calcium/calmodulin-dependent protein kinase 1 family, a subfamily of the serine/threonine kinases. The encoded protein is a component of the calcium-regulated calmodulin-dependent protein kinase cascade. It has been associated with multiple processes including regulation of granulocyte function, activation of CREB-dependent gene transcription, aldosterone synthesis, differentiation and activation of neutrophil cells, and apoptosis of erythroleukemia cells. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.

Source: NCBI Gene 57118 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 63 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 25 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_153498

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19341
Approved symbol	CAMK1D
Name	calcium/calmodulin dependent protein kinase ID
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	CKLiK
Ensembl gene	ENSG00000183049
Ensembl biotype	protein_coding
OMIM	607957
Entrez	57118

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000378845, ENST00000487696, ENST00000619168

RefSeq mRNA: 3 — MANE Select: NM_153498 NM_001351032, NM_020397, NM_153498

CCDS: CCDS7091, CCDS7092

Canonical transcript exons

ENST00000619168 — 11 exons

Exon	Start	End
ENSE00001294036	12769673	12769799
ENSE00001301838	12824465	12824552
ENSE00001316120	12816250	12816328
ENSE00001329570	12666736	12666810
ENSE00001330591	12553225	12553356
ENSE00001707369	12814195	12814307
ENSE00001755682	12791158	12791233
ENSE00001763642	12760948	12761086
ENSE00003717045	12828769	12835545
ENSE00003738811	12349547	12349910
ENSE00003746286	12825573	12825690

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3914 / max 503.3302, expressed in 1298 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103917	4.9876	611
103914	4.4129	1045
103918	1.4339	450
103915	0.4875	277
103916	0.3756	183
103913	0.2878	120
103920	0.2051	55
103919	0.1446	68
205726	0.0566	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	97.96	gold quality
parietal lobe	UBERON:0001872	97.77	gold quality
postcentral gyrus	UBERON:0002581	97.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.42	gold quality
cerebellar vermis	UBERON:0004720	97.16	gold quality
superior frontal gyrus	UBERON:0002661	96.24	gold quality
entorhinal cortex	UBERON:0002728	95.99	gold quality
nipple	UBERON:0002030	95.30	gold quality
primary visual cortex	UBERON:0002436	95.24	gold quality
trigeminal ganglion	UBERON:0001675	95.02	gold quality
endothelial cell	CL:0000115	95.01	gold quality
occipital lobe	UBERON:0002021	94.75	gold quality
dorsal root ganglion	UBERON:0000044	94.47	gold quality
pharyngeal mucosa	UBERON:0000355	94.43	gold quality
superior surface of tongue	UBERON:0007371	93.88	gold quality
pons	UBERON:0000988	93.68	gold quality
lateral globus pallidus	UBERON:0002476	92.94	gold quality
synovial joint	UBERON:0002217	92.55	gold quality
frontal cortex	UBERON:0001870	91.93	gold quality
buccal mucosa cell	CL:0002336	91.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.74	gold quality
neocortex	UBERON:0001950	91.56	gold quality
prefrontal cortex	UBERON:0000451	91.44	gold quality
cerebral cortex	UBERON:0000956	91.25	gold quality
superior vestibular nucleus	UBERON:0007227	91.23	gold quality
epithelium of nasopharynx	UBERON:0001951	91.19	gold quality
gingiva	UBERON:0001828	91.13	gold quality
temporal lobe	UBERON:0001871	91.08	gold quality
saphenous vein	UBERON:0007318	90.96	gold quality
right frontal lobe	UBERON:0002810	90.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	3446.35
E-HCAD-25	yes	80.62
E-CURD-119	yes	7.29
E-GEOD-137537	yes	4.98
E-MTAB-6386	no	259.21
E-GEOD-81608	no	8.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

46 targeting CAMK1D, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-6773-3P	98.17	65.51	1213

Literature-anchored findings (GeneRIF, showing 11)

• role of CKLiK in specific granulocyte effector functions such as phagocytosis, respiratory burst, migration, and adhesion (PMID:15840691)
• CAMK1D as a novel amplified oncogene linked to epithelial-mesenchymal transition in breast cancer, with elevated expression in invasive carcinomas compared to carcinoma in situ (PMID:19383354)
• A significant association of rs10906115 in CDC123/CAMK1D and rs1359790 near SPRY2 was identified with type 2 diabetes in a Japanese population. (PMID:21909839)
• Association to type 2 diabetes was found for rs13266634 (SLC30A8), rs7923837 (HHEX), rs10811661 (CDKN2A/2B), rs4402960 (IGF2BP2), rs12779790 (CDC123/CAMK1D), and rs2237892 (KCNQ1). (PMID:22923468)
• Substantiation of the roles of CAMK1D and CDKAL1 in gluconeogenic and glyconeogenic pathways in primary human hepatocytes. (PMID:23840313)
• identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan (PMID:25410890)
• There were no statistically significant differences in the distribution of CDC123/CAMK1D rs12779790 genotypes and alleles between women with gestational diabetes mellitus and healthy pregnant women. (PMID:28079868)
• Cross-talk between eIF5A and CAMK1D enhances proliferation. (PMID:29533498)
• CAMK1D Triggers Immune Resistance of Human Tumor Cells Refractory to Anti-PD-L1 Treatment. (PMID:32665263)
• Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population. (PMID:33127268)
• CircPRKCI regulates proliferation, migration and cycle of lung adenocarcinoma cells by targeting miR-219a-5p-regulated CAMK1D. (PMID:33660800)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	camk1db	ENSDARG00000017446
danio_rerio	camk1da	ENSDARG00000074905
mus_musculus	Camk1d	ENSMUSG00000039145
rattus_norvegicus	Camk1d	ENSRNOG00000017882
drosophila_melanogaster	CaMKI	FBGN0016126

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390)

Protein

Protein identifiers

Calcium/calmodulin-dependent protein kinase type 1D — Q8IU85 (reviewed: Q8IU85)

Alternative names: CaM kinase I delta, CaMKI-like protein kinase

All UniProt accessions (2): Q8IU85, Q5SQQ7

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed. Highly and mostly expressed in polymorphonuclear leukocytes (neutrophilic and eosinophilic granulocytes) while little or no expression is observed in monocytes and lymphocytes.

Activity regulation. Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-180 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-180 results in several fold increase in total activity. Unlike CaMK4, may be unable to exhibit autonomous activity after Ca(2+)/calmodulin activation.

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.

Induction. Expression increases upon treatment of EC cells with DMSO and retinoic acid. Induced by KCL in PC12 cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IU85-1	1	yes
Q8IU85-2	2

RefSeq proteins (3): NP_001337961, NP_065130, NP_705718* (*=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 (45 total): helix 13, strand 9, turn 6, region of interest 3, modified residue 2, mutagenesis site 2, binding site 2, chain 1, domain 1, cross-link 1, splice variant 1, sequence variant 1, short sequence motif 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6T29	X-RAY DIFFRACTION	1.48
6T28	X-RAY DIFFRACTION	1.55
8BFM	X-RAY DIFFRACTION	1.7
6QP5	X-RAY DIFFRACTION	1.9
8BFS	X-RAY DIFFRACTION	1.95
6T6F	X-RAY DIFFRACTION	1.97
2JC6	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IU85-F1	77.13	0.48

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): 144 (proton acceptor)

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

Post-translational modifications (3): 122, 180, 113

Mutagenesis-validated functional residues (2):

Position	Phenotype
52	catalytically inactive form.
180	loss of ionomycin-induced activation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 403 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_RESPIRATORY_BURST, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_CREB_TRANSCRIPTION_FACTOR_ACTIVITY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (14): inflammatory response (GO:0006954), signal transduction (GO:0007165), nervous system development (GO:0007399), regulation of neuron projection development (GO:0010975), positive regulation of neuron projection development (GO:0010976), obsolete positive regulation of CREB transcription factor activity (GO:0032793), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of phagocytosis (GO:0050766), regulation of dendrite development (GO:0050773), positive regulation of respiratory burst (GO:0060267), regulation of granulocyte chemotaxis (GO:0071622), positive regulation of neutrophil chemotaxis (GO:0090023), 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 (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection development	2
regulation of neuron projection development	2
apoptotic process	2
regulation of apoptotic process	2
protein kinase activity	2
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
regulation of plasma membrane bounded cell projection organization	1
positive regulation of cell projection organization	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
dendrite development	1
regulation of developmental process	1
positive regulation of metabolic process	1
respiratory burst	1
regulation of respiratory burst	1
regulation of leukocyte chemotaxis	1
granulocyte chemotaxis	1
neutrophil chemotaxis	1
positive regulation of granulocyte chemotaxis	1
regulation of neutrophil chemotaxis	1
positive regulation of neutrophil migration	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

Protein interactions and networks

STRING

1949 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMK1D	CDC123	O75794	873
CAMK1D	CALM1	P02593	804
CAMK1D	CALML3	P27482	785
CAMK1D	CALML5	Q9NZT1	774
CAMK1D	CALML4	Q96GE6	771
CAMK1D	CALML6	Q8TD86	769
CAMK1D	JAZF1	Q86VZ6	699
CAMK1D	CDKAL1	Q5VV42	669
CAMK1D	ADAMTS9	Q9P2N4	642
CAMK1D	TSPAN8	P19075	641
CAMK1D	HHEX	Q03014	624
CAMK1D	SLC30A8	Q8IWU4	623
CAMK1D	CYP11B2	P19099	598
CAMK1D	MTNR1B	P49286	583
CAMK1D	WFS1	O76024	582
CAMK1D	IGF2BP2	Q9Y6M1	582

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CAMK1D	CAMK1	psi-mi:“MI:0915”(physical association)	0.620
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
CAMK1D	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
GNRHR	CAMK1D	psi-mi:“MI:0915”(physical association)	0.400
POT1	CAMK1D	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	CFAP418	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	ASAH1	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	BNIP3L	psi-mi:“MI:0915”(physical association)	0.370
CDC25A	CAMK1D	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	CUL3	psi-mi:“MI:0915”(physical association)	0.370
TNFSF13	CAMK1D	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	GMFG	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	CFTR	psi-mi:“MI:0915”(physical association)	0.370
STK17B	H2AZ1	psi-mi:“MI:0914”(association)	0.350
CAMK1	PSMD12	psi-mi:“MI:0914”(association)	0.350
TRIB3	TIMM8A	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CAMK1D	SLC27A2	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
CAMK1D	CALM1	psi-mi:“MI:0914”(association)	0.350
STPG3	LONP1	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
TREML2	DNM1L	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
CER1	PC	psi-mi:“MI:0914”(association)	0.350
COMTD1	TRIO	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
EPHA1	ENC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (87): CAMK1 (Affinity Capture-MS), CAMK1G (Affinity Capture-MS), ZG16B (Affinity Capture-MS), QPCTL (Affinity Capture-MS), MUC7 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CST4 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), CAMK1D (Proximity Label-MS), CAMK1 (Affinity Capture-MS), CAMK1G (Affinity Capture-MS), MUC7 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CAMK1D (Affinity Capture-MS)

ESM2 similar proteins: A8X6H4, O70150, O75582, P10665, P11275, P11798, P18652, P18653, P18654, P28583, P51812, Q13557, Q14012, Q15349, Q2HJF7, Q38869, Q38871, Q38872, Q39016, Q42396, Q54CY9, Q54SJ5, Q5F3L1, Q5R4K3, Q5RCC4, Q5ZKI0, Q63450, Q63531, Q6DEH3, Q6GLS4, Q6P2M8, Q6PFQ0, Q6PHZ2, Q7TPS0, Q869W6, Q8BW96, Q8IU85, Q8RWL2, Q8VDF3, Q91YS8

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
CAMKK1	“up-regulates activity”	CAMK1D	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	34
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
584050	NC_000010.10:g.(?12833157)(13178866_?)del	Pathogenic
599307	Single allele	Pathogenic
3376508	NM_153498.4(CAMK1D):c.450_451del (p.Leu151fs)	Likely pathogenic

SpliceAI

7099 predictions. Top by Δscore:

Variant	Effect	Δscore
10:12349906:GGAAC:G	donor_gain	1.0000
10:12349907:GAAC:G	donor_gain	1.0000
10:12349907:GAACG:G	donor_gain	1.0000
10:12349908:A:T	donor_gain	1.0000
10:12349911:G:GG	donor_gain	1.0000
10:12553216:T:TA	acceptor_gain	1.0000
10:12553220:CACA:C	acceptor_loss	1.0000
10:12553221:ACAGC:A	acceptor_gain	1.0000
10:12553222:C:G	acceptor_gain	1.0000
10:12553222:CA:C	acceptor_loss	1.0000
10:12553223:A:AG	acceptor_gain	1.0000
10:12553223:AGC:A	acceptor_gain	1.0000
10:12553223:AGCG:A	acceptor_gain	1.0000
10:12553223:AGCGG:A	acceptor_gain	1.0000
10:12553224:G:GA	acceptor_gain	1.0000
10:12553224:G:T	acceptor_loss	1.0000
10:12553224:GC:G	acceptor_gain	1.0000
10:12553224:GCG:G	acceptor_gain	1.0000
10:12553224:GCGG:G	acceptor_gain	1.0000
10:12553224:GCGGG:G	acceptor_gain	1.0000
10:12553320:A:T	donor_gain	1.0000
10:12553352:AGAAA:A	donor_gain	1.0000
10:12553353:GAAA:G	donor_gain	1.0000
10:12553353:GAAAG:G	donor_gain	1.0000
10:12553354:AAA:A	donor_gain	1.0000
10:12553355:AA:A	donor_gain	1.0000
10:12553355:AAGTA:A	donor_loss	1.0000
10:12553356:AG:A	donor_loss	1.0000
10:12553357:G:GG	donor_gain	1.0000
10:12553357:GTAA:G	donor_loss	1.0000

AlphaMissense

2555 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:12349906:G:A	G30R	1.000
10:12349906:G:C	G30R	1.000
10:12349907:G:A	G30E	1.000
10:12349907:G:T	G30V	1.000
10:12553226:G:A	G32R	1.000
10:12553226:G:C	G32R	1.000
10:12553226:G:T	G32W	1.000
10:12553227:G:A	G32E	1.000
10:12553227:G:C	G32A	1.000
10:12553227:G:T	G32V	1.000
10:12553232:T:A	F34I	1.000
10:12553232:T:C	F34L	1.000
10:12553232:T:G	F34V	1.000
10:12553233:T:C	F34S	1.000
10:12553233:T:G	F34C	1.000
10:12553234:T:A	F34L	1.000
10:12553234:T:G	F34L	1.000
10:12553235:T:C	S35P	1.000
10:12553236:C:A	S35Y	1.000
10:12553236:C:T	S35F	1.000
10:12553241:G:A	V37M	1.000
10:12553241:G:C	V37L	1.000
10:12553241:G:T	V37L	1.000
10:12553242:T:A	V37E	1.000
10:12553251:C:A	A40D	1.000
10:12553281:C:A	A50D	1.000
10:12553286:A:C	K52Q	1.000
10:12553286:A:G	K52E	1.000
10:12553287:A:T	K52M	1.000
10:12553288:G:C	K52N	1.000

dbSNP variants (sampled 300 via entrez): RS1000000275 (10:12555205 C>G,T), RS1000008803 (10:12737120 C>T), RS1000012658 (10:12578259 T>G), RS1000012916 (10:12494557 A>T), RS1000032501 (10:12383348 C>T), RS1000035593 (10:12379300 G>A), RS1000047213 (10:12506119 A>G), RS1000050023 (10:12663503 A>G), RS1000067167 (10:12593573 A>G), RS1000068768 (10:12453173 T>A), RS1000071838 (10:12763677 A>C,T), RS1000073315 (10:12538492 A>G), RS1000074589 (10:12367032 A>G), RS1000075472 (10:12811533 C>G), RS1000081564 (10:12394487 G>A)

Disease associations

OMIM: gene MIM:607957 | disease phenotypes: MIM:613435, MIM:137760, MIM:146255

GenCC curated gene-disease

Mondo (4): intellectual disability (MONDO:0001071), amyotrophic lateral sclerosis type 12 (MONDO:0013264), OPTN-related open angle glaucoma (MONDO:0100553), hypoparathyroidism-deafness-renal disease syndrome (MONDO:0007797)

Orphanet (3): Amyotrophic lateral sclerosis (Orphanet:803), Hypoparathyroidism-sensorineural deafness-renal disease syndrome (Orphanet:2237), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000167_2	Type 2 diabetes	1.000000e-10
GCST000796_1	Type 2 diabetes	1.000000e-08
GCST001762_244	Obesity-related traits	1.000000e-06
GCST001762_48	Obesity-related traits	6.000000e-07
GCST001762_758	Obesity-related traits	1.000000e-06
GCST001762_773	Obesity-related traits	4.000000e-06
GCST001890_4	QT interval (drug interaction)	6.000000e-06
GCST001960_5	Eating disorders	4.000000e-06
GCST001961_10	Anorexia nervosa	6.000000e-06
GCST003400_48	Type 2 diabetes	1.000000e-12
GCST003445_3	Response to cyclophosphamide in systemic lupus erythematosus with lupus nephritis	9.000000e-07
GCST003560_14	Coronary artery aneurysm in Kawasaki disease	5.000000e-06
GCST004641_27	Borderline personality disorder	3.000000e-06
GCST004904_158	Body mass index	1.000000e-09
GCST004904_49	Body mass index	7.000000e-09
GCST005047_11	Type 2 diabetes	2.000000e-06
GCST005337_14	Headache	5.000000e-10
GCST005413_13	Type 2 diabetes	4.000000e-10
GCST006801_10	Type 2 diabetes	5.000000e-06
GCST007847_39	Type 2 diabetes	8.000000e-27
GCST007847_62	Type 2 diabetes	3.000000e-07
GCST008103_160	Bipolar disorder	6.000000e-06
GCST008529_61	Tea consumption	2.000000e-06
GCST008595_138	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-09
GCST008839_575	Height	5.000000e-09
GCST009379_97	Type 2 diabetes	2.000000e-32
GCST009524_195	Household income (MTAG)	5.000000e-09
GCST010118_179	Type 2 diabetes	1.000000e-61
GCST010219_13	Attention deficit hyperactivity disorder (inattention symptoms)	3.000000e-07
GCST010396_126	Gut microbiota (bacterial taxa, hurdle binary method)	1.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement
EFO:0005189	respiratory quotient
EFO:0004682	QT interval
EFO:0004340	body mass index
EFO:0010091	tea consumption measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009695	household income
EFO:0007874	gut microbiome measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C537907	Barakat syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5073 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

25 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 160,027 (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
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2
CHEMBL1908397	KW-2449	1
CHEMBL1980391	RG-1530	1
CHEMBL494089	GSK-690693	1
CHEMBL574738	AST-487	1

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10737062	Efficacy	3	losartan	Essential hypertension
rs10752271	Efficacy	3	losartan	Essential hypertension

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10737062	CAMK1D	3	2.75	1	losartan
rs10752271	CAMK1D	3	2.75	1	losartan
rs7896283	CAMK1D, MIR4481		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CAMK1 family

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

Ligand	Action	Affinity	Parameter
bosutinib	Inhibition	7.04	pIC50

Binding affinities (BindingDB)

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

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 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
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 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

266 potent at pChembl≥5 of 294 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.69	IC50	0.206	nM	STAUROSPORINE
9.61	IC50	0.243	nM	STAUROSPORINE
9.53	IC50	0.298	nM	STAUROSPORINE
8.96	Kd	1.1	nM	STAUROSPORINE
8.70	Kd	2	nM	STAUROSPORINE
8.40	IC50	4	nM	CHEMBL5753821
8.40	IC50	4	nM	CHEMBL6043667
8.40	Ki	3.981	nM	CHEMBL1980995
8.30	IC50	5	nM	CHEMBL5826196
8.30	IC50	5	nM	CHEMBL5918789
8.22	IC50	6	nM	CHEMBL5826007
8.22	IC50	6	nM	CHEMBL5996247
8.22	IC50	6	nM	CHEMBL6050954
8.15	IC50	7	nM	CHEMBL6001498
8.15	IC50	7	nM	CHEMBL5769875
8.15	IC50	7	nM	CHEMBL5968013
8.10	IC50	8	nM	CHEMBL4635883
8.10	IC50	8	nM	CHEMBL4640712
8.10	IC50	8	nM	CHEMBL5855802
8.10	IC50	8	nM	CHEMBL5772374
8.10	IC50	8	nM	CHEMBL5842788
8.00	IC50	10	nM	CHEMBL6043672
8.00	IC50	10	nM	CHEMBL5997642
8.00	IC50	10	nM	CHEMBL5868746
8.00	IC50	10	nM	CHEMBL5889394
8.00	IC50	10	nM	CHEMBL5747336
7.96	IC50	11	nM	CHEMBL4635883
7.96	IC50	11	nM	CHEMBL5762522
7.92	IC50	12	nM	CHEMBL5751699
7.82	IC50	15	nM	CHEMBL6037089
7.72	IC50	19	nM	CHEMBL4633229
7.72	IC50	19	nM	CHEMBL5865780
7.72	IC50	19	nM	CHEMBL5893977
7.68	IC50	21	nM	CHEMBL5749972
7.66	IC50	22	nM	CHEMBL4633229
7.66	IC50	22	nM	CHEMBL6026564
7.66	IC50	22	nM	CHEMBL5896182
7.64	IC50	23	nM	CHEMBL5988346
7.64	IC50	23	nM	CHEMBL6034515
7.62	IC50	24	nM	CHEMBL5838873
7.62	IC50	24	nM	CHEMBL5860251
7.62	IC50	24	nM	CHEMBL6064219
7.60	IC50	25	nM	CHEMBL6043878
7.58	IC50	26	nM	CHEMBL4640712
7.57	IC50	27	nM	CHEMBL4632457
7.57	IC50	27	nM	CHEMBL5997030
7.57	IC50	27	nM	CHEMBL5761324
7.55	IC50	28	nM	CHEMBL4632457
7.55	IC50	28	nM	CHEMBL5741412
7.55	IC50	28	nM	CHEMBL5886387

PubChem BioAssay actives

75 with measured affinity, of 1293 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	1715430: Inhibition of human CAMK1D using KKALRRQETVDAL as substrate by [gamma-33P]-ATP assay	ic50	0.0002	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[3,5-bis(2-cyanopropan-2-yl)anilino]pyrimidine-5-carboxamide	1668856: Inhibition of HA-tagged CAMK1D (unknown origin) expressed in human MDA-MB-231 cells assessed as reduction in CAMK1D autophosphorylation measured after 4 hrs by Western blot analysis	ic50	0.0080	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[[2,6-di(propan-2-yl)-4-pyridinyl]amino]pyrimidine-5-carboxamide	1668838: Inhibition of human CAMK1D using KKALRRQETVDAL as substrate in presence of [gamma-33P]-ATP by hotspot kinase assay	ic50	0.0080	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[3-(2-cyanopropan-2-yl)-5-phenylanilino]pyrimidine-5-carboxamide	1668856: Inhibition of HA-tagged CAMK1D (unknown origin) expressed in human MDA-MB-231 cells assessed as reduction in CAMK1D autophosphorylation measured after 4 hrs by Western blot analysis	ic50	0.0190	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-(3-tert-butyl-5-methylsulfonylanilino)pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.0270	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	507853: Binding affinity to CAMK1D	kd	0.0470	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-(3-phenylanilino)pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.0470	uM
Bosutinib	507450: Inhibition of CAMK1D	ic50	0.0920	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[3-(2-cyanopropan-2-yl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.0960	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-(3-methylsulfonylanilino)pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.1010	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[3,5-di(propan-2-yl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.1150	uM
Ruxolitinib	625118: Binding constant for CAMK1D kinase domain	kd	0.1200	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668838: Inhibition of human CAMK1D using KKALRRQETVDAL as substrate in presence of [gamma-33P]-ATP by hotspot kinase assay	ic50	0.1790	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	625118: Binding constant for CAMK1D kinase domain	kd	0.2000	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	625118: Binding constant for CAMK1D kinase domain	kd	0.2300	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-(3-tert-butylanilino)pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.2770	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-(3,5-ditert-butylanilino)pyrimidine-5-carboxamide	1668838: Inhibition of human CAMK1D using KKALRRQETVDAL as substrate in presence of [gamma-33P]-ATP by hotspot kinase assay	ic50	0.3990	uM
2-(2-aminoethylamino)-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.4320	uM
2-[(3S)-3-aminopiperidin-1-yl]-4-[3,5-bis(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.4550	uM
Fedratinib	625118: Binding constant for CAMK1D kinase domain	kd	0.4600	uM
2-(3-aminopiperidin-1-yl)-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.4850	uM
Sunitinib	435393: Binding constant for CAMK1D kinase domain	kd	0.5100	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625118: Binding constant for CAMK1D kinase domain	kd	0.5300	uM
Midostaurin	435393: Binding constant for CAMK1D kinase domain	kd	0.6700	uM
2-[2-aminoethyl(methyl)amino]-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	0.8510	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	435393: Binding constant for CAMK1D kinase domain	kd	0.9700	uM
Momelotinib	2183888: Inhibition of CAMK1 delta (unknown origin)	ic50	1.0000	uM
2-[(3R)-3-aminopiperidin-1-yl]-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668848: Inhibition of recombinant human full-length His-tagged CAMK1D expressed in baculovirus expression system using autocamtide-2 as substrate preincubated for 15 mins followed by ATP addition and measured after 2 hrs by ADP-glo luminescence assay	ic50	1.3500	uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one	256584: Average Binding Constant for CAMK1D; NA=Not Active at 10 uM	kd	1.4000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625118: Binding constant for CAMK1D kinase domain	kd	1.5000	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625118: Binding constant for CAMK1D kinase domain	kd	1.5000	uM
Tofacitinib	625118: Binding constant for CAMK1D kinase domain	kd	1.6000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625118: Binding constant for CAMK1D kinase domain	kd	2.2000	uM
Upadacitinib	2189490: Inhibition of CAMK1D (unknown origin) by TR-FRET assay	ic50	2.3000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625118: Binding constant for CAMK1D kinase domain	kd	2.4000	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-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]-N-methylbenzamide	507853: Binding affinity to CAMK1D	kd	2.4000	uM
N-propyl-4-[[4-(2,2,2-trifluoroethylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]benzamide	1440101: Inhibition of human CAMK1D (unknown origin) after 60 mins by TR-FRET assay	ic50	2.4800	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625118: Binding constant for CAMK1D kinase domain	kd	2.5000	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	256584: Average Binding Constant for CAMK1D; NA=Not Active at 10 uM	kd	2.6000	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769532: Binding affinity to CAMK1D (unknown origin)	kd	2.8000	uM
1-pentyl-4-(2-phenylmethoxyphenyl)imidazol-2-amine;hydrochloride	1734146: Inhibition of wild-type human CAMK1delta using KKALRRQETVDAL peptide as substrate in presence of Ca2+ calmodulin and [gamma-33P]-ATP by radiometric hotspot kinase assay	ic50	3.0000	uM
2-[methyl-[2-(methylamino)ethyl]amino]-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide	1668838: Inhibition of human CAMK1D using KKALRRQETVDAL as substrate in presence of [gamma-33P]-ATP by hotspot kinase assay	ic50	3.4900	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256584: Average Binding Constant for CAMK1D; NA=Not Active at 10 uM	kd	3.8000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625118: Binding constant for CAMK1D kinase domain	kd	4.4000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435393: Binding constant for CAMK1D kinase domain	kd	4.9000	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625118: Binding constant for CAMK1D kinase domain	kd	5.3000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625118: Binding constant for CAMK1D kinase domain	kd	5.4000	uM
Neratinib	625118: Binding constant for CAMK1D kinase domain	kd	5.6000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625118: Binding constant for CAMK1D kinase domain	kd	6.6000	uM
8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)-2-(4-piperidin-4-ylpiperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine	674639: Inhibition of CAMK1D by FRET assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	5
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
bisphenol A	decreases methylation, increases expression, affects cotreatment, affects methylation	2
trichostatin A	affects cotreatment, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, decreases expression, increases reaction	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1

ChEMBL screening assays

276 unique, capped per target: 274 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011057	Binding	Inhibition of CaMK1delta at 100 nM relative to control	Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. — J Med Chem
CHEMBL1963811	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CAMK1D	PubChem BioAssay data set

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D7LJ	Ubigene A-549 CAMK1D KO	Cancer cell line	Male
CVCL_D8IA	Ubigene HCT 116 CAMK1D KO	Cancer cell line	Male
CVCL_D9AT	Ubigene HEK293 CAMK1D KO	Transformed cell line	Female
CVCL_D9Z7	Ubigene HeLa CAMK1D KO	Cancer cell line	Female
CVCL_SG64	HAP1 CAMK1D (-) 1	Cancer cell line	Male
CVCL_SG65	HAP1 CAMK1D (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders