DCLK2

Summary

DCLK2 (doublecortin like kinase 2, HGNC:19002) is a protein-coding gene on chromosome 4q31.23-q31.3, encoding Serine/threonine-protein kinase DCLK2 (Q8N568). Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family.

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. Mouse studies show that the DCX gene, another family member, and this gene share function in the establishment of hippocampal organization and that their absence results in a severe epileptic phenotype and lethality, as described in human patients with lissencephaly. Multiple alternatively spliced transcript variants have been identified.

Source: NCBI Gene 166614 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 110 total — 1 likely-pathogenic
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001040260

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19002
Approved symbol	DCLK2
Name	doublecortin like kinase 2
Location	4q31.23-q31.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC45428, DCDC3, DCDC3B, DCK2
Ensembl gene	ENSG00000170390
Ensembl biotype	protein_coding
OMIM	613166
Entrez	166614

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296550, ENST00000302176, ENST00000411937, ENST00000506325, ENST00000507694, ENST00000634233, ENST00000635524, ENST00000897298, ENST00000897299, ENST00000897300, ENST00000953289, ENST00000953290, ENST00000953291, ENST00000953292

RefSeq mRNA: 3 — MANE Select: NM_001040260 NM_001040260, NM_001040261, NM_001410852

CCDS: CCDS34076, CCDS47142, CCDS93647

Canonical transcript exons

ENST00000296550 — 16 exons

Exon	Start	End
ENSE00001081795	150232682	150232828
ENSE00001081796	150239742	150239875
ENSE00001081799	150240399	150240476
ENSE00001081801	150224501	150224558
ENSE00001081802	150248305	150248385
ENSE00001081803	150247603	150247699
ENSE00001154074	150221677	150221785
ENSE00001201615	150232337	150232456
ENSE00001201662	150102478	150102812
ENSE00001201667	150203795	150203889
ENSE00001259332	150220703	150220778
ENSE00001411160	150249568	150249684
ENSE00001429067	150078445	150079448
ENSE00003468987	150198002	150198103
ENSE00003564876	150193138	150193240
ENSE00003665760	150256020	150257438

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 95.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1181 / max 223.0619, expressed in 1002 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49974	2.6350	466
49971	1.2951	409
49977	0.9442	453
49976	0.7327	279
49975	0.5542	200
49973	0.3880	186
49970	0.3263	150
49978	0.1462	72
49972	0.0964	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.83	gold quality
secondary oocyte	CL:0000655	93.96	gold quality
cortical plate	UBERON:0005343	93.30	gold quality
amygdala	UBERON:0001876	93.24	gold quality
nucleus accumbens	UBERON:0001882	93.12	gold quality
caudate nucleus	UBERON:0001873	92.92	gold quality
anterior cingulate cortex	UBERON:0009835	92.82	gold quality
right frontal lobe	UBERON:0002810	92.71	gold quality
embryo	UBERON:0000922	92.38	gold quality
ganglionic eminence	UBERON:0004023	92.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.65	gold quality
hypothalamus	UBERON:0001898	91.63	gold quality
putamen	UBERON:0001874	91.57	gold quality
prefrontal cortex	UBERON:0000451	91.28	gold quality
Ammon’s horn	UBERON:0001954	90.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.88	gold quality
neocortex	UBERON:0001950	90.71	gold quality
frontal cortex	UBERON:0001870	90.53	gold quality
temporal lobe	UBERON:0001871	90.41	gold quality
cerebral cortex	UBERON:0000956	90.37	gold quality
forebrain	UBERON:0001890	90.14	gold quality
brain	UBERON:0000955	89.23	gold quality
spinal cord	UBERON:0002240	89.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.06	gold quality
corpus callosum	UBERON:0002336	89.02	gold quality
substantia nigra	UBERON:0002038	88.58	gold quality
midbrain	UBERON:0001891	87.68	gold quality
entorhinal cortex	UBERON:0002728	87.47	gold quality
superior frontal gyrus	UBERON:0002661	87.43	gold quality
ventricular zone	UBERON:0003053	87.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	64.98
E-HCAD-25	yes	21.39
E-CURD-119	yes	19.16
E-GEOD-93593	no	10.77
E-ANND-3	no	4.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting DCLK2, 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-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-2110	99.96	66.68	1930
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-657	99.48	66.02	848
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-330-5P	98.73	67.63	1788

Literature-anchored findings (GeneRIF, showing 1)

• Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma. (PMID:38211588)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dclk2	ENSMUSG00000028078
rattus_norvegicus	Dclk2	ENSRNOG00000016550

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), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Serine/threonine-protein kinase DCLK2 — Q8N568 (reviewed: Q8N568)

Alternative names: CaMK-like CREB regulatory kinase 2, Doublecortin domain-containing protein 3B, Doublecortin-like and CAM kinase-like 2, Doublecortin-like kinase 2

All UniProt accessions (4): Q8N568, A0A0U1RR70, A0A0U1RRD0, G5E9L9

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm.

Subunit / interactions. Binds to and stabilizes microtubules. Interacts with MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK9/JNK2, PPP1R9B/NEURABIN-2 and actin.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in the brain, heart and eyes.

Post-translational modifications. Autophosphorylated.

Domain organisation. The doublecortin domains are involved in the colocalization with microtubules.

Miscellaneous. By homology to mouse isoform 2.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N568-1	1	yes
Q8N568-2	2
Q8N568-3	3

RefSeq proteins (3): NP_001035350, NP_001035351, NP_001397781 (=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

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 (28 total): compositionally biased region 6, modified residue 4, sequence variant 4, domain 3, region of interest 3, binding site 2, splice variant 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N568-F1	70.37	0.30

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): 515 (proton acceptor)

Ligand- & substrate-binding residues (2): 400–408; 423

Post-translational modifications (4): 61, 362, 647, 666

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, GCANCTGNY_MYOD_Q6, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_HIPPOCAMPUS_DEVELOPMENT, TCF11_01, GOBP_PALLIUM_DEVELOPMENT, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, MYOD_Q6, GOBP_HEAD_DEVELOPMENT

GO Biological Process (8): microtubule cytoskeleton organization (GO:0000226), hippocampus development (GO:0021766), pyramidal neuron development (GO:0021860), protein localization to nucleus (GO:0034504), intracellular signal transduction (GO:0035556), negative regulation of protein localization to nucleus (GO:1900181), protein phosphorylation (GO:0006468), central nervous system development (GO:0007417)

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

GO Cellular Component (2): cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
cytoskeleton organization	1
microtubule-based process	1
pallium development	1
limbic system development	1
anatomical structure development	1
pyramidal neuron differentiation	1
forebrain neuron development	1
protein localization to organelle	1
signal transduction	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
negative regulation of protein localization	1
phosphorylation	1
protein modification process	1
nervous system development	1
system development	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCLK2	KLHL36	Q8N4N3	581
DCLK2	PPP1R9B	Q96SB3	524
DCLK2	TANC2	Q9HCD6	471
DCLK2	CRTC2	Q53ET0	461
DCLK2	SLC15A5	A6NIM6	422
DCLK2	MAPK8	P45983	407
DCLK2	CALML3	P27482	405
DCLK2	CALML6	Q8TD86	405
DCLK2	CALML4	Q96GE6	405
DCLK2	CALML5	Q9NZT1	405
DCLK2	HSP90AA1	P07900	400
DCLK2	HPSE2	Q8WWQ2	399
DCLK2	CALM1	P02593	394
DCLK2	HSPA1A	P08107	392
DCLK2	CTXND1	A0A1B0GTU2	366

IntAct

21 interactions, top by confidence:

A	B	Type	Score
DCLK2	YWHAE	psi-mi:“MI:0915”(physical association)	0.560
	DCLK2	psi-mi:“MI:0407”(direct interaction)	0.440
DCLK2	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	DCLK2	psi-mi:“MI:0915”(physical association)	0.400
DCLK2	KLHL15	psi-mi:“MI:0915”(physical association)	0.400
KLHL15	DCLK2	psi-mi:“MI:0915”(physical association)	0.400
SFN	DCLK2	psi-mi:“MI:0915”(physical association)	0.400
DCLK2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
TSC22D3	DCLK2	psi-mi:“MI:0915”(physical association)	0.370
STK32C	ILVBL	psi-mi:“MI:0914”(association)	0.350
DCLK2	ZBTB5	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
FBLIM1	DCLK1	psi-mi:“MI:0914”(association)	0.350
DCTN1	NACA	psi-mi:“MI:2364”(proximity)	0.270
BTG3	DCLK2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): DCLK2 (Affinity Capture-RNA), DCLK2 (Synthetic Lethality), DCLK2 (Proximity Label-MS), DCLK2 (Affinity Capture-RNA), DCLK2 (Affinity Capture-RNA), CCDC57 (Two-hybrid), DCLK2 (Affinity Capture-Western), KLHL15 (Affinity Capture-Western), DCLK2 (Proximity Label-MS), DCLK2 (Affinity Capture-MS), DCLK2 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), SCO2 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), IMPDH2 (Affinity Capture-MS)

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

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8WXF6, E9PT87, F1M0Z1, G4SLH0, O02827, O08875, O43293, O44997, O54784, O60229, O62305, O70150, O75962, O88764, O94768, O94806, P07313, P08414, P10911, P13234, P18652, P18653, P18654, P20689, P22216, P25323, P29294, P51812, P53355, P97924, Q00168, Q0KHT7, Q0KL02, Q14012, Q15139, Q15418

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	85
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1697205	NC_000004.11:g.(?149081621)(151082561_?)del	Likely pathogenic

SpliceAI

3901 predictions. Top by Δscore:

Variant	Effect	Δscore
4:150102472:TTTTA:T	acceptor_loss	1.0000
4:150102476:AGGT:A	acceptor_gain	1.0000
4:150102477:GGT:G	acceptor_gain	1.0000
4:150102477:GGTG:G	acceptor_gain	1.0000
4:150102477:GGTGA:G	acceptor_gain	1.0000
4:150102809:GCAG:G	donor_gain	1.0000
4:150102810:CAGG:C	donor_loss	1.0000
4:150102811:AGG:A	donor_loss	1.0000
4:150102812:GGT:G	donor_loss	1.0000
4:150102813:G:GG	donor_gain	1.0000
4:150102813:GTAA:G	donor_loss	1.0000
4:150102814:T:G	donor_loss	1.0000
4:150181301:TGGA:T	donor_gain	1.0000
4:150193238:GTG:G	donor_gain	1.0000
4:150203781:T:A	acceptor_gain	1.0000
4:150203788:T:TA	acceptor_gain	1.0000
4:150203789:G:A	acceptor_gain	1.0000
4:150221673:GCA:G	acceptor_loss	1.0000
4:150221674:CAGGT:C	acceptor_loss	1.0000
4:150221675:A:AG	acceptor_gain	1.0000
4:150221675:AG:A	acceptor_gain	1.0000
4:150221675:AGGT:A	acceptor_gain	1.0000
4:150221676:G:A	acceptor_loss	1.0000
4:150221676:G:GT	acceptor_gain	1.0000
4:150221676:GG:G	acceptor_gain	1.0000
4:150221676:GGT:G	acceptor_gain	1.0000
4:150221676:GGTG:G	acceptor_gain	1.0000
4:150221676:GGTGT:G	acceptor_gain	1.0000
4:150221781:GACAG:G	donor_gain	1.0000
4:150221782:ACAGG:A	donor_loss	1.0000

AlphaMissense

4997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:150079254:T:C	F76S	1.000
4:150079256:T:G	Y77D	1.000
4:150079264:C:A	N79K	1.000
4:150079264:C:G	N79K	1.000
4:150079283:G:C	G86R	1.000
4:150079344:T:C	L106P	1.000
4:150079374:T:C	L116P	1.000
4:150079386:T:A	V120D	1.000
4:150102486:T:G	Y144D	1.000
4:150102492:T:C	C146R	1.000
4:150102494:T:G	C146W	1.000
4:150102549:T:A	W165R	1.000
4:150102549:T:C	W165R	1.000
4:150102642:C:T	P196S	1.000
4:150102643:C:A	P196H	1.000
4:150102643:C:G	P196R	1.000
4:150102647:G:C	K197N	1.000
4:150102647:G:T	K197N	1.000
4:150102649:T:C	L198S	1.000
4:150102652:T:A	V199E	1.000
4:150102658:T:A	V201E	1.000
4:150102670:G:A	G205E	1.000
4:150102682:G:C	R209T	1.000
4:150102682:G:T	R209I	1.000
4:150102683:A:C	R209S	1.000
4:150102683:A:T	R209S	1.000
4:150102688:C:A	A211D	1.000
4:150102700:T:A	L215H	1.000
4:150102700:T:C	L215P	1.000
4:150102703:T:A	L216Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000013072 (4:150247634 C>G,T), RS1000023961 (4:150208045 G>A), RS1000025310 (4:150163449 T>C), RS1000041695 (4:150121721 A>G), RS1000045844 (4:150115698 A>G), RS1000047004 (4:150117952 C>T), RS1000049952 (4:150158553 C>G,T), RS1000057011 (4:150214186 A>T), RS10000923 (4:150115055 T>C), RS1000109881 (4:150121908 G>A), RS10001334 (4:150152368 A>G), RS1000135856 (4:150199827 G>C), RS1000137889 (4:150121416 A>G), RS1000140216 (4:150252991 G>A,T), RS1000141610 (4:150165347 G>C)

Disease associations

OMIM: gene MIM:613166 | disease phenotypes: MIM:177735

GenCC curated gene-disease

Mondo (1): autosomal dominant pseudohypoaldosteronism type 1 (MONDO:0008329)

Orphanet (2): Renal pseudohypoaldosteronism type 1 (Orphanet:171871), Pseudohypoaldosteronism type 1 (Orphanet:756)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001523_4	Visceral adipose tissue adjusted for BMI	1.000000e-06
GCST002228_1	Social autistic-like traits	1.000000e-06
GCST003470_3	Coronary artery disease	8.000000e-10
GCST003471_2	Myocardial infarction	6.000000e-06
GCST003809_2	Response to selective serotonin reuptake inhibitors and depression	1.000000e-07
GCST005790_95	Rosacea symptom severity	8.000000e-06
GCST007946_1	Psychological resilience (self-assessed)	6.000000e-09
GCST008258_1	Alcohol use disorder (consumption score)	1.000000e-08
GCST008258_14	Alcohol use disorder (consumption score)	3.000000e-08
GCST009856_34	Leukocyte telomere length	3.000000e-06
GCST009996_10	HDL cholesterol levels	5.000000e-07

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005426	autism spectrum disorder symptom
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0009180	rosacea severity measurement
EFO:0009945	psychological resilience measurement
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009458	alcohol use disorder measurement
EFO:0007805	HDL cholesterol change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5519 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 113,982 (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
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL445813	AT-7519	2	2,614
CHEMBL575448	BMS-754807	2	406
CHEMBL296468	BMS-387032	1	2,075

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
DCLK1-IN-1	Inhibition	7.51	pIC50
XMD8-92	Inhibition	6.72	pKd

Binding affinities (BindingDB)

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

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
BMS-387072	KD	1800 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

ChEMBL bioactivities

23 potent at pChembl≥5 of 23 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	Kd	10	nM	CHEMBL1673039
7.80	Kd	16	nM	TAE-684
7.14	Kd	73	nM	STAUROSPORINE
7.08	IC50	83.5	nM	STAUROSPORINE
7.05	IC50	88.2	nM	STAUROSPORINE
7.03	IC50	94.4	nM	STAUROSPORINE
6.72	Kd	190	nM	CHEMBL1673046
6.43	Kd	370	nM	CRIZOTINIB
6.12	Kd	760	nM	RUXOLITINIB
6.06	Kd	870	nM	FEDRATINIB
6.00	Kd	1000	nM	BMS-387032
6.00	Kd	990	nM	PHA-665752
5.58	Kd	2600	nM	AT-7519
5.57	Kd	2700	nM	SUNITINIB
5.44	Kd	3600	nM	BMS-754807
5.43	Kd	3700	nM	SU-014813
5.35	Kd	4500	nM	JNJ-7706621
5.35	Kd	4500	nM	LESTAURTINIB

PubChem BioAssay actives

22 with measured affinity, of 625 total; 15 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
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	570546: Binding affinity to DCAMKL2 by immobilized ligand displacement assay	kd	0.0100	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	624814: Binding constant for DCAMKL2 kinase domain	kd	0.0160	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	435651: Binding constant for DCAMKL2 kinase domain	kd	0.0730	uM
2-[2-ethoxy-4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one	2160994: Binding affinity to DCAMKL2 (unknown origin) assessed as dissociation constant by ATP-competition binding assay	kd	0.1900	uM
Crizotinib	624814: Binding constant for DCAMKL2 kinase domain	kd	0.3700	uM
Ruxolitinib	624814: Binding constant for DCAMKL2 kinase domain	kd	0.7600	uM
Fedratinib	624814: Binding constant for DCAMKL2 kinase domain	kd	0.8700	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	624814: Binding constant for DCAMKL2 kinase domain	kd	0.9900	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435651: Binding constant for DCAMKL2 kinase domain	kd	1.0000	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624814: Binding constant for DCAMKL2 kinase domain	kd	2.6000	uM
Sunitinib	435651: Binding constant for DCAMKL2 kinase domain	kd	2.7000	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	2167414: Binding affinity to DCAMKL2 (unknown origin) by phage based competition assay	kd	3.6000	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	624814: Binding constant for DCAMKL2 kinase domain	kd	3.7000	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	624814: Binding constant for DCAMKL2 kinase domain	kd	4.5000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435651: Binding constant for DCAMKL2 kinase domain	kd	4.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1

ChEMBL screening assays

216 unique, capped per target: 216 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1034097	Binding	Inhibition of DCAMKL2 at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XN16	HAP1 DCLK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03630094	PHASE1	COMPLETED	Plasma and Intrapulmonary Concentrations Study of WCK 5222
NCT06435936	PHASE1	ACTIVE_NOT_RECRUITING	A Study to Assess the Safety of SAB-176 to Prevent the Flu, Given IM in Healthy Adults Compared With Placebo
NCT06806995	PHASE1	COMPLETED	A Single-center, Open-label, Study Evaluating Safety and Pharmacokinetics of Single Doses of Zidebactam-Cefepime and Metronidazole Alone or in Combination.
NCT03931668	EARLY_PHASE1	UNKNOWN	Tolerance, PK and PD Effects Study of TPN-672 in Chinese Healthy Volunteers