DCLK1

Summary

DCLK1 (doublecortin like kinase 1, HGNC:2700) is a protein-coding gene on chromosome 13q13.3, encoding Serine/threonine-protein kinase DCLK1 (O15075). Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain.

This gene encodes a member of the protein kinase superfamily and the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, a C-terminal serine/threonine protein kinase domain, which shows substantial homology to Ca2+/calmodulin-dependent protein kinase, and a serine/proline-rich domain in between the doublecortin and the protein kinase domains, which mediates multiple protein-protein interactions. The microtubule-polymerizing activity of the encoded protein is independent of its protein kinase activity. The encoded protein is involved in several different cellular processes, including neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. This gene is up-regulated by brain-derived neurotrophic factor and associated with memory and general cognitive abilities. Multiple transcript variants generated by two alternative promoter usage and alternative splicing have been reported, but the full-length nature and biological validity of some variants have not been defined. These variants encode different isoforms, which are differentially expressed and have different kinase activities.

Source: NCBI Gene 9201 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 35 total — 3 pathogenic
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001330071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2700
Approved symbol	DCLK1
Name	doublecortin like kinase 1
Location	13q13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0369, DCLK, DCDC3A
Ensembl gene	ENSG00000133083
Ensembl biotype	protein_coding
OMIM	604742
Entrez	9201

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000255448, ENST00000360631, ENST00000379892, ENST00000379893, ENST00000460982, ENST00000477664, ENST00000486239, ENST00000615680, ENST00000879266, ENST00000879268, ENST00000914190, ENST00000914194

RefSeq mRNA: 6 — MANE Select: NM_001330071 NM_001195415, NM_001195416, NM_001195430, NM_001330071, NM_001330072, NM_004734

CCDS: CCDS55895, CCDS73561, CCDS81762, CCDS9354

Canonical transcript exons

ENST00000360631 — 17 exons

Exon	Start	End
ENSE00000680572	35810835	35810968
ENSE00000680573	35822729	35822875
ENSE00000680576	35828250	35828307
ENSE00000817072	35805699	35805779
ENSE00000817073	35808224	35808320
ENSE00000817078	35827635	35827754
ENSE00000817080	35836033	35836141
ENSE00000817083	35839092	35839176
ENSE00000938675	36111869	36112215
ENSE00001003745	35947358	35947457
ENSE00001093760	35871224	35871340
ENSE00001183960	35809018	35809095
ENSE00001406064	36125762	36126156
ENSE00003578867	35854499	35854593
ENSE00003614284	35793366	35793479
ENSE00003737572	35768652	35774699
ENSE00003901953	36131114	36131382

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.6523 / max 717.6807, expressed in 1026 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136757	5.0847	384
136767	4.1003	646
136765	2.9991	547
136755	1.5973	217
136764	1.1185	269
136766	0.6842	233
136756	0.5889	135
136768	0.5265	249
136769	0.4554	219
136759	0.4540	155

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.19	gold quality
frontal pole	UBERON:0002795	99.08	gold quality
cortical plate	UBERON:0005343	98.82	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.26	gold quality
substantia nigra pars compacta	UBERON:0001965	98.25	gold quality
occipital lobe	UBERON:0002021	98.19	gold quality
middle temporal gyrus	UBERON:0002771	98.16	gold quality
superior vestibular nucleus	UBERON:0007227	97.95	gold quality
primary visual cortex	UBERON:0002436	97.93	gold quality
orbitofrontal cortex	UBERON:0004167	97.68	gold quality
parietal lobe	UBERON:0001872	97.47	gold quality
pons	UBERON:0000988	97.07	gold quality
postcentral gyrus	UBERON:0002581	97.05	gold quality
prefrontal cortex	UBERON:0000451	96.91	gold quality
entorhinal cortex	UBERON:0002728	96.91	gold quality
medulla oblongata	UBERON:0001896	96.78	gold quality
superior frontal gyrus	UBERON:0002661	96.72	gold quality
ventral tegmental area	UBERON:0002691	96.66	gold quality
lateral globus pallidus	UBERON:0002476	96.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.10	gold quality
frontal cortex	UBERON:0001870	95.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.76	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.57	gold quality
cerebral cortex	UBERON:0000956	95.54	gold quality
neocortex	UBERON:0001950	95.53	gold quality
ganglionic eminence	UBERON:0004023	95.15	gold quality
skin of hip	UBERON:0001554	95.09	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2370.25
E-HCAD-25	yes	86.43
E-HCAD-35	yes	62.64
E-ANND-3	yes	24.36
E-MTAB-9388	yes	11.83
E-GEOD-109979	no	163.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, TP53

miRNA regulators (miRDB)

273 targeting DCLK1, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
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-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• genomic organization underlying the splice variants of DCLK and the expression profile of two splice variants affecting the kinase domain of DCLK and CPG16 (candidate plasticity gene 16). (PMID:11884394)
• high-quality wild-type crystals of doublecortin-like kinase were obtained and a complete native data set was collected to 1.5 A resolution (PMID:12595708)
• an examination of the binding sites on this protein (PMID:12692530)
• Together, our results suggest that silencing the DCLK splice variants DCL and DCLK-long induces apoptosis in NB cells. (PMID:20228126)
• Data show that siRNA-mediated knockdown of DCAMKL-1 in pancreatic cancer cells induced microRNA miR-200a, an EMT inhibitor, along with downregulation of EMT-associated transcription factors. (PMID:21285251)
• Eight suggestive significant loci were detected with a series of genes expressed within the inner ear that underlie the auditory function, such as: DCLK1, PTPRD, GRM8, CMIP. (PMID:21493956)
• the progressive increase of DCAMKL-1 expression in Barrett’s esophagus from dysplasia to esophageal adenocarcinoma (PMID:21916995)
• High DCAMKL1 is associated with HCV-induced hepatocarcinogenesis. (PMID:21937640)
• Several DCLK1 variants were associated with disease phenotypes for rs7989807 in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3’UTR (SCZ+BP). (PMID:22539971)
• DCAMKL-1 marks a subset of colorectal stem cells, as well as a subset of entero-endocrine cells. (PMID:22749579)
• Dclk1 distinguishes between tumor and normal stem cells in the intestine. (PMID:23202126)
• DCAMKL1 represses osteoblast activation by antagonizing Runx2, the master transcription factor in osteoblasts. (PMID:23918955)
• DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer. (PMID:24040120)
• Human pancreatic ductal adenocarcinoma cells contain morphologically and functionally distinct subpopulations, expressing DCLK1, that have cancer stem cell-like properties. (PMID:24096005)
• DCLK1 mRNA levels were considerably reduced during FLV treatment. (PMID:24260365)
• Potential exist for DCLK1 as a colorectal cancer biomarker for early detection, but may also have clinical implications regarding the previously proposed therapy toward DCLK1-positive cancer cells. (PMID:24384857)
• RNA interference-mediated silencing of DCLK1 triggers apoptotic cell death of colon cancer cells in vitro and in vivo. (PMID:24626093)
• XMD8-92 treatment results in inhibition of DCLK1 and downstream oncogenic pathways. (PMID:24880079)
• Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with Barrett’s esophagus and esophageal adenocarcinoma. (PMID:25283374)
• Data indicate that doublecortin-like kinase 1 (DCLK1) is overexpressed and has a unique methylation signature in renal clear cell carcinoma (RCC). (PMID:25605241)
• the higher expression level of DCLK1 in patients undergoing CRT can propose it as a more relevant candidate among CSC markers comparing to Lgr5 for colorectal cancer patients. (PMID:25631749)
• Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells. (PMID:25723399)
• results provide new insights into the molecular mechanism of the hepatitis B/C-virus induced liver inflammation and tumorigenesis via DCLK1-controlled networks (PMID:25948779)
• DCLK1 promoter methylationis associated with lung cancer. (PMID:26311076)
• Data suggest that doublecortin and CaM kinase-like 1 protein short-transcripts (DCLK1-S) may represent an important target for preventing/inhibiting colon-cancers, and for eliminating colon-cancer-stem-cells (CSCs). (PMID:26447334)
• DCLK1 controls these complex cellular signaling pathways to regulate hepatocellular carcinoma growth, and may be used as a prognostic biomarker. (PMID:26468984)
• DCLK1 expression could aid in the prognostication and management of breast cancer with neuroendocrine differentiation. (PMID:26621833)
• Results showed the mechanism in which miR-137 regulates the expression of DCLK1, and demonstrated the opposite expression patterns of miR-137/DCLK1 in human non-small cell lung carcinoma and colon cancer stem cells. (PMID:26747706)
• DCLK1 is essential for the invasive and metastatic properties of pancreatic cancer stem cells. (PMID:26764906)
• first evidence for the suppressive activity of miR-613 in hepatocellular carcinoma, which is causally linked to targeting of DCLK1 (PMID:27049311)
• DCLK1 up-regulation may play a contributory role in colorectal cancer metastasis and poor prognosis via activation of EMT. DCLK1 may serve as an independent predictor for CRC prognosis. (PMID:27520310)
• Biochemical and structural characterization of DCLK1 allowed for the mapping of cancer-causing mutations within the kinase domain. (PMID:27545623)
• DCLK1 induction and its overexpression following hepatic injury are likely to contribute to tumorigenesis including maintenance and dissemination of tumor cells in circulation. (PMID:27694285)
• Increased expression of stromal DCLK1 was detected in endometriotic tissue compared to endometriosis patient endometrium. Stromal expression of DCLK1 was increased in endometrium of endometriosis patients compared to controls. (PMID:27881125)
• MSX1 and DCLK1 might be used in colorectal cancer detection or as target of cancer therapies. (PMID:27966796)
• DCLK1 plays crucial role in the regulation of epithelial-mesenchymal transition.DCLK1 is highly expressed in pancreatic neuroendocrine tumor. (PMID:28179411)
• DCLK1 has been identified as a potential target for miR-448 to regulate lung squamous cell carcinoma cells growth. (PMID:28320089)
• DCLK1 is a prognostic biomarker for shortened survival. Secondly, through inhibition of DCLK1, it may serve as a therapeutic target as well (PMID:28351564)
• DCLK1 expression was observed in tumor cells in patients with pathological stage I non-small cell lung cancer (NSCLC)and was correlated with adverse prognosis, especially in patients with adenocarcinoma. DCLK1 may be a potential new therapeutic target (PMID:28382517)
• Generated a (doublecortin like kinase 1) DCLK1-S-specific polyclonal antibody (S-isoform specific), and studied its use in screening of colon cancer after colonoscopy. (PMID:28414327)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dclk1a	ENSDARG00000018856
danio_rerio	dclk1b	ENSDARG00000104664
mus_musculus	Dclk1	ENSMUSG00000027797
rattus_norvegicus	Dclk1	ENSRNOG00000032922

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Serine/threonine-protein kinase DCLK1 — O15075 (reviewed: O15075)

Alternative names: Doublecortin domain-containing protein 3A, Doublecortin-like and CAM kinase-like 1, Doublecortin-like kinase 1

All UniProt accessions (3): A0A9L9PXT2, O15075, Q5VZY9

UniProt curated annotations — full annotation on UniProt →

Function. Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system.

Tissue specificity. In fetal tissues, highly expressed in brain, detectable in lung and liver, but not in kidney. In adult tissues, expressed ubiquitously in the brain, detectable in the heart, liver, spleen, thymus, prostate, testis, ovary, small intestine and colon. The type A isoforms seem to be expressed predominantly in fetal brain whereas type B isoforms are expressed abundantly in both fetal and adult brain.

Induction. Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).

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

Isoforms (4)

UniProt ID	Names	Canonical?
O15075-1	2, AL	yes
O15075-2	1, AS
O15075-3	3, BS
O15075-4	4, BL

RefSeq proteins (6): NP_001182344, NP_001182345, NP_001182359, NP_001317000, NP_001317001, NP_004725 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR003533	Doublecortin_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR036572	Doublecortin_dom_sf	Homologous_superfamily

Pfam: PF00069, PF03607

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

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 (80 total): modified residue 19, helix 18, strand 14, turn 8, sequence variant 5, compositionally biased region 4, domain 3, splice variant 3, binding site 2, region of interest 2, chain 1, active site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
1MG4	X-RAY DIFFRACTION	1.5
1MFW	X-RAY DIFFRACTION	1.6
5JZJ	X-RAY DIFFRACTION	1.71
7F3G	X-RAY DIFFRACTION	2.1
6KYQ	X-RAY DIFFRACTION	2.14
6KYR	X-RAY DIFFRACTION	2.21
7KX6	X-RAY DIFFRACTION	2.5
5JZN	X-RAY DIFFRACTION	2.85
7KXW	X-RAY DIFFRACTION	3
7KX8	X-RAY DIFFRACTION	3.1
1UF0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15075-F1	72.69	0.33

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): 511 (proton acceptor)

Ligand- & substrate-binding residues (2): 396–404; 419

Post-translational modifications (19): 32, 36, 46, 305, 307, 330, 332, 334, 337, 347, 352, 353, 355, 364, 376, 520, 726, 735, 738

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 352 (showing top): GNF2_RTN1, CREL_01, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEURON_PROJECTION_EXTENSION, MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TTTGTAG_MIR520D, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, MODULE_317, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, chr13q13, STARK_HYPPOCAMPUS_22Q11_DELETION_UP

GO Biological Process (12): protein phosphorylation (GO:0006468), nervous system development (GO:0007399), central nervous system development (GO:0007417), response to virus (GO:0009615), endosomal transport (GO:0016197), protein localization to nucleus (GO:0034504), intracellular signal transduction (GO:0035556), axon extension (GO:0048675), neuron migration (GO:0001764), cell differentiation (GO:0030154), axoneme assembly (GO:0035082), retina development in camera-type eye (GO:0060041)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), microtubule binding (GO:0008017), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell projection (GO:0042995), neuron projection (GO:0043005)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	2
intracellular anatomical structure	2
protein kinase activity	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
nervous system development	1
response to other organism	1
vesicle-mediated transport	1
intracellular transport	1
protein localization to organelle	1
signal transduction	1
axonogenesis	1
neuron projection extension	1
cell migration	1
generation of neurons	1
cellular developmental process	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
camera-type eye development	1
anatomical structure development	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
tubulin binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

3330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCLK1	NBEA	Q8NFP9	781
DCLK1	MAB21L1	Q13394	764
DCLK1	CALML3	P27482	746
DCLK1	CALML6	Q8TD86	745
DCLK1	CALML4	Q96GE6	745
DCLK1	CALML5	Q9NZT1	744
DCLK1	CALM1	P02593	742
DCLK1	TRPM5	Q9NZQ8	728
DCLK1	LGR5	O75473	718
DCLK1	NOTCH1	P46531	637
DCLK1	POU2F3	Q9UKI9	627
DCLK1	ZSCAN18	Q8TBC5	613
DCLK1	KRT19	P08727	607
DCLK1	PROM1	O43490	570
DCLK1	CHGA	P10645	556

IntAct

111 interactions, top by confidence:

A	B	Type	Score
DCX	ZBTB5	psi-mi:“MI:0914”(association)	0.670
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
DCLK1	DCX	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
DCX	DCLK1	psi-mi:“MI:0914”(association)	0.530
DCLK1	SNCA	psi-mi:“MI:0915”(physical association)	0.400
	DCLK1	psi-mi:“MI:0915”(physical association)	0.400
KLHL15	DCLK1	psi-mi:“MI:0915”(physical association)	0.400
DCLK1		psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
TNK2	DCLK1	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	SPTBN2	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
HAX1	DNM1L	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
DGUOK	BIN1	psi-mi:“MI:0914”(association)	0.350
CDCA8	DCLK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Co-fractionation), DCLK1 (Proximity Label-MS), DCLK1 (Proximity Label-MS), DCLK1 (Proximity Label-MS), DCLK1 (Proximity Label-MS), DCLK1 (Proximity Label-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS), DCLK1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9X0, A8WUG4, F1M7Y5, O08875, O13310, O15075, O19111, O97627, P00518, P07934, P09217, P21146, P25098, P26817, P26818, P26819, P31325, P34722, P35626, P41743, P54645, P54646, P83099, Q02111, Q02956, Q04735, Q05513, Q09137, Q09639, Q11179, Q12706, Q13131, Q16816, Q19266, Q21734, Q28948, Q39019, Q3UYH7, Q5EG47, Q5R4K9

Diamond homologs: A1A5Q6, A1CHL6, A1CX69, A2BD05, A2QIL5, A6RYB8, A6ZU07, A7F0W2, A7KAL2, A7TIZ4, A8XQD5, D3ZHP7, D7UQM5, F4IRW0, F4JBP3, I1RNG8, J4W0G2, O15075, O22932, O70405, O75385, O80902, O94547, O94806, P0CP70, P0CP71, P22209, P48479, P53104, P59895, P87248, P92937, Q0CLX3, Q0UY20, Q10LQ2, Q10SC8, Q19469, Q1DN93, Q1LUA6, Q23023

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DCLK1	“up-regulates activity”	MACC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	65.3×	2e-09
Activation of BAD and translocation to mitochondria	6	63.4×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	56.0×	4e-08
Activation of BH3-only proteins	6	41.4×	2e-07
RHO GTPases activate PKNs	7	30.8×	1e-07
Intrinsic Pathway for Apoptosis	6	24.4×	4e-06
Apoptosis	7	16.3×	5e-06
SARS-CoV-1-host interactions	6	14.6×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	21.1×	3e-04
microtubule cytoskeleton organization	7	8.2×	4e-03
intracellular protein localization	8	8.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1527764	GRCh37/hg19 13q13.3(chr13:35757546-36398671)x1	Pathogenic
3063273	GRCh37/hg19 13q13.3(chr13:36143563-36524660)x1	Pathogenic
4682824	GRCh37/hg19 13q13.2-13.3(chr13:35060777-36582063)x1	Pathogenic

SpliceAI

4927 predictions. Top by Δscore:

Variant	Effect	Δscore
13:35774700:C:CC	acceptor_gain	1.0000
13:35774710:C:CT	acceptor_gain	1.0000
13:35774711:A:AC	acceptor_gain	1.0000
13:35774711:A:C	acceptor_gain	1.0000
13:35793364:A:AC	donor_gain	1.0000
13:35793365:C:CC	donor_gain	1.0000
13:35793365:CTG:C	donor_gain	1.0000
13:35793494:A:C	acceptor_gain	1.0000
13:35808318:CTT:C	acceptor_gain	1.0000
13:35808321:C:CC	acceptor_gain	1.0000
13:35808335:G:T	acceptor_gain	1.0000
13:35808921:T:A	donor_gain	1.0000
13:35810830:TTTAC:T	donor_loss	1.0000
13:35810831:TTAC:T	donor_loss	1.0000
13:35810832:TAC:T	donor_loss	1.0000
13:35810833:A:AC	donor_gain	1.0000
13:35810833:AC:A	donor_gain	1.0000
13:35810833:ACCCA:A	donor_loss	1.0000
13:35810834:C:CC	donor_gain	1.0000
13:35810834:C:T	donor_loss	1.0000
13:35810834:CC:C	donor_gain	1.0000
13:35810966:CAC:C	acceptor_gain	1.0000
13:35810968:CCTA:C	acceptor_loss	1.0000
13:35810969:CTAA:C	acceptor_loss	1.0000
13:35822722:CTCTT:C	donor_loss	1.0000
13:35822723:TCTTA:T	donor_loss	1.0000
13:35822724:CTTAC:C	donor_loss	1.0000
13:35822725:TTA:T	donor_loss	1.0000
13:35822726:TAC:T	donor_loss	1.0000
13:35822727:A:AG	donor_loss	1.0000

AlphaMissense

4807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:35805707:A:G	W646R	1.000
13:35805707:A:T	W646R	1.000
13:35808250:A:G	W613R	1.000
13:35808250:A:T	W613R	1.000
13:35809023:G:C	F587L	1.000
13:35809023:G:T	F587L	1.000
13:35809025:A:G	F587L	1.000
13:35809027:G:T	P586Q	1.000
13:35809036:C:A	G583V	1.000
13:35809036:C:T	G583D	1.000
13:35809045:A:G	L580P	1.000
13:35809063:C:T	G574D	1.000
13:35809064:C:G	G574R	1.000
13:35809071:C:A	W571C	1.000
13:35809071:C:G	W571C	1.000
13:35809073:A:G	W571R	1.000
13:35809073:A:T	W571R	1.000
13:35809078:T:A	D569V	1.000
13:35809078:T:G	D569A	1.000
13:35809079:C:A	D569Y	1.000
13:35809079:C:G	D569H	1.000
13:35810866:A:C	Y553D	1.000
13:35810866:A:G	Y553H	1.000
13:35810871:G:T	P551Q	1.000
13:35810877:C:A	G549V	1.000
13:35810877:C:T	G549D	1.000
13:35810878:C:A	G549C	1.000
13:35810878:C:G	G549R	1.000
13:35810878:C:T	G549S	1.000
13:35810913:G:T	A537D	1.000

dbSNP variants (sampled 300 via entrez): RS1000002557 (13:35920805 G>A), RS1000015064 (13:36024933 C>A,T), RS1000016779 (13:35837621 A>G), RS1000017260 (13:35897986 T>C), RS1000019940 (13:36081314 A>C), RS1000043052 (13:35790045 G>T), RS1000051625 (13:36124769 A>C,G), RS1000052658 (13:35806835 C>A,T), RS1000082265 (13:36072638 C>A,G), RS1000084556 (13:35962481 A>C,G), RS1000090254 (13:36006140 A>C), RS1000095413 (13:35849249 T>C), RS1000101138 (13:35860828 G>A), RS1000106642 (13:35976924 A>C), RS1000130547 (13:35995843 T>C)

Disease associations

OMIM: gene MIM:604742 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000086_2	Heart rate variability traits	8.000000e-06
GCST000700_9	Vertical cup-disc ratio	1.000000e-08
GCST001263_3	Height	7.000000e-07
GCST001762_479	Obesity-related traits	5.000000e-06
GCST001928_3	Pediatric non-alcoholic fatty liver disease activity score	7.000000e-06
GCST002762_15	Optic cup area	2.000000e-11
GCST002762_30	Optic cup area	4.000000e-08
GCST003262_596	Post bronchodilator FEV1	4.000000e-06
GCST004137_23	Optic cup area	3.000000e-14
GCST004137_39	Optic cup area	2.000000e-15
GCST006088_31	Familial squamous cell lung carcinoma	1.000000e-07
GCST006102_8	Interleukin-10 levels	3.000000e-07
GCST009404_15	Optic cup area	5.000000e-18
GCST009412_12	Vertical cup-disc ratio	3.000000e-11
GCST009723_48	Vertical cup-disc ratio (adjusted for vertical disc diameter)	9.000000e-18
GCST009724_51	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-23
GCST010396_171	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06
GCST012490_540	Femur bone mineral density x serum urate levels interaction	4.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004314	forced expiratory volume
EFO:0006953	family history of lung cancer
EFO:0004750	interleukin 10 measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0007874	gut microbiome measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5465224 (PROTEIN-PROTEIN INTERACTION), CHEMBL5683 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 163,710 (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
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL513909	BI-2536	2	895
CHEMBL575448	BMS-754807	2	406
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL494089	GSK-690693	1	2,061

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — DCAMKL family

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

Ligand	Action	Affinity	Parameter
DCLK1-IN-1	Inhibition	6.55	pIC50

Binding affinities (BindingDB)

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

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
BMS-387072	KD	1800 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
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 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
13-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-2,5,9-trimethyl-4-thia-2,6,9,12,14-pentazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),5,10,12-pentaen-8-one	IC50	3610 nM	US-12365696: Small-molecule focal adhesion kinase (FAK) inhibitors
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

126 potent at pChembl≥5 of 126 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL1673048
8.92	Kd	1.2	nM	CHEMBL1673039
8.70	IC50	2	nM	CHEMBL4646447
8.70	IC50	2	nM	CHEMBL4643632
8.52	IC50	3	nM	CHEMBL4636475
8.52	IC50	3	nM	CHEMBL4634326
8.40	IC50	4	nM	CHEMBL4645267
8.31	Kd	4.9	nM	TAE-684
8.00	IC50	10	nM	CHEMBL4640016
7.96	IC50	11	nM	CHEMBL1673041
7.96	IC50	11	nM	CHEMBL1673039
7.85	IC50	14	nM	CHEMBL4636072
7.77	IC50	17	nM	CHEMBL4639395
7.66	IC50	22	nM	CHEMBL2381340
7.60	Kd	25	nM	CHEMBL4554938
7.58	IC50	26	nM	CHEMBL1673053
7.55	IC50	27.9	nM	CHEMBL4554938
7.50	IC50	32	nM	CHEMBL4648947
7.44	IC50	36	nM	CHEMBL4644273
7.43	IC50	37	nM	CHEMBL4634025
7.42	IC50	37.9	nM	CHEMBL4639395
7.40	Ki	39.81	nM	TAE-684
7.40	Ki	39.81	nM	CHEMBL1981047
7.28	IC50	52	nM	CHEMBL1673042
7.24	IC50	58	nM	CHEMBL4647792
7.24	IC50	57.2	nM	CHEMBL4639395
7.21	Kd	61	nM	CHEMBL5193786
7.17	Kd	68	nM	RUXOLITINIB
7.15	IC50	71	nM	CHEMBL1673052
7.10	IC50	80	nM	CHEMBL4641263
7.01	IC50	97	nM	CHEMBL1673040
6.98	IC50	104	nM	CHEMBL4648454
6.96	IC50	109	nM	CHEMBL4649424
6.96	IC50	111	nM	CHEMBL3904942
6.96	Kd	110	nM	STAUROSPORINE
6.90	IC50	126	nM	CHEMBL4646882
6.90	Ki	125.9	nM	CHEMBL1993661
6.81	IC50	154	nM	CHEMBL1673051
6.77	IC50	171.3	nM	CHEMBL5639361
6.76	IC50	173	nM	STAUROSPORINE
6.73	IC50	187	nM	CHEMBL1673047
6.72	Kd	190	nM	FEDRATINIB
6.67	IC50	214	nM	CHEMBL4645722
6.63	IC50	233	nM	STAUROSPORINE
6.50	Ki	316.2	nM	CHEMBL2000114
6.50	Ki	316.2	nM	CHEMBL1971029
6.48	Kd	330	nM	CRIZOTINIB
6.44	IC50	361	nM	STAUROSPORINE
6.43	Kd	370	nM	SUNITINIB
6.39	IC50	411	nM	CHEMBL4649318

PubChem BioAssay actives

68 with measured affinity, of 913 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
4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0010	uM
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	570545: Binding affinity to DCAMKL1 by immobilized ligand displacement assay	kd	0.0012	uM
N-[4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]phenyl]methanesulfonamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0020	uM
4-[(5-ethyl-11-methyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0020	uM
N-[4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxyphenyl]methanesulfonamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0030	uM
5-ethyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-11-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0030	uM
11-benzyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0040	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	624966: Binding constant for DCAMKL1 kinase domain	kd	0.0049	uM
3-methoxy-4-[[11-methyl-6-oxo-5-(2,2,2-trifluoroethyl)pyrimido[4,5-b][1,4]benzodiazepin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0100	uM
2-(2-methoxy-4-morpholin-4-ylanilino)-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0110	uM
11-cyclobutyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0140	uM
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-11-methyl-5-(2,2,2-trifluoroethyl)pyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0170	uM
11-cyclopentyl-2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0220	uM
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide	2189149: Binding affinity to DCAMKL1 (unknown origin) assessed as dissociation constant	kd	0.0250	uM
11-cyclopentyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0260	uM
11-butan-2-yl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0320	uM
N-[4-[(5-ethyl-11-methyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-3-methoxyphenyl]methanesulfonamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0360	uM
2-[4-(4-hydroxypiperidin-1-yl)-2-methylanilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0370	uM
2-(2-methoxy-4-piperazin-1-ylanilino)-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0520	uM
2-[2-methoxy-4-[4-(1-methylpiperidin-4-yl)piperazine-1-carbonyl]anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0580	uM
4-(3,6-dichloro-2-fluorobenzoyl)-N-(1-methylpyrazol-4-yl)-1H-pyrrole-2-carboxamide	1909528: Binding affinity to wild-type human partial length DCLK1 (L270 to A662 residues) expressed in mammalian expression system by Kinomescan assay	kd	0.0610	uM
Ruxolitinib	624966: Binding constant for DCAMKL1 kinase domain	kd	0.0680	uM
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-11-propan-2-ylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0710	uM
N-[3-methoxy-4-[[11-methyl-6-oxo-5-(2,2,2-trifluoroethyl)pyrimido[4,5-b][1,4]benzodiazepin-2-yl]amino]phenyl]methanesulfonamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0800	uM
2-[4-(4-hydroxypiperidin-1-yl)-2-methoxyanilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.0970	uM
2-[2-methoxy-4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.1040	uM
2-[4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.1090	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	435284: Binding constant for DCAMKL1 kinase domain	kd	0.1100	uM
3-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]benzenesulfonamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.1110	uM
3-methoxy-4-[(11-methyl-6-oxo-5-propan-2-ylpyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]-N-(1-methylpiperidin-4-yl)benzamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.1260	uM
11-ethyl-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.1540	uM
2-N-(2-methoxyphenyl)-6-N-(2-propan-2-ylsulfonylphenyl)-7H-purine-2,6-diamine	2143233: Inhibition of DCLK1 (unknown origin) preincubated for 10 mins followed by substrate/ATP addition measured after 60 mins by mobility shift assay	ic50	0.1713	uM
4-[(5,11-dimethyl-6-oxopyrimido[4,5-b][1,4]benzodiazepin-2-yl)amino]benzenesulfonamide	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.1870	uM
Fedratinib	624966: Binding constant for DCAMKL1 kinase domain	kd	0.1900	uM
11-methyl-2-[4-(4-methylpiperazin-1-yl)-2-propan-2-yloxyanilino]-5-(2,2,2-trifluoroethyl)pyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.2140	uM
Crizotinib	624966: Binding constant for DCAMKL1 kinase domain	kd	0.3300	uM
Sunitinib	435284: Binding constant for DCAMKL1 kinase domain	kd	0.3700	uM
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-11-methyl-5-propan-2-ylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.4110	uM
2-[4-(4-hydroxypiperidin-1-yl)-2-propan-2-yloxyanilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.5100	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624966: Binding constant for DCAMKL1 kinase domain	kd	0.5400	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	435284: Binding constant for DCAMKL1 kinase domain	kd	0.5500	uM
2-[2-ethoxy-4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	1652716: Inhibition of recombinant human N-terminal His6-tagged DCLK1 (G351 to H689 residues) expressed in Escherichia coli BL21 DE3 using 5-FAM-KKLRRTLSVA-COOH as substrate measured after 2 hrs by mobility shift assay	ic50	0.7160	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	624966: Binding constant for DCAMKL1 kinase domain	kd	1.4000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435284: Binding constant for DCAMKL1 kinase domain	kd	1.6000	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	2167410: Binding affinity to DCAMKL1 (unknown origin) by phage based competition assay	kd	1.7000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624966: Binding constant for DCAMKL1 kinase domain	kd	2.0000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435284: Binding constant for DCAMKL1 kinase domain	kd	2.1000	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	624966: Binding constant for DCAMKL1 kinase domain	kd	2.4000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435284: Binding constant for DCAMKL1 kinase domain	kd	2.5000	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	624966: Binding constant for DCAMKL1 kinase domain	kd	4.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	8
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, increases expression	2
entinostat	decreases expression, increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Vehicle Emissions	decreases methylation, increases abundance, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Asbestos, Crocidolite	decreases expression, decreases methylation	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
propionaldehyde	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
trichostatin A	decreases expression, increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1

ChEMBL screening assays

150 unique, capped per target: 149 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5369606	Binding	PROTAC activity at VHL/DCLK1 in human A-375 cells assessed as induction of DCLK1 degradation at 6 to 500 nM incubated for 12 hrs by western bot analysis	Design, Synthesis, and Biological Evaluation of Proteolysis-Targeting Chimeras as Highly Selective and Efficient Degraders of Extracellular Signal-Regulated Kinase 5. — J Med Chem
CHEMBL1963822	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: DCAMKL1	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9D1	Ubigene HEK293 DCLK1 KO	Transformed cell line	Female
CVCL_SK46	HAP1 DCLK1 (-) 1	Cancer cell line	Male
CVCL_SK47	HAP1 DCLK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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