SIK2

Summary

SIK2 (salt inducible kinase 2, HGNC:21680) is a protein-coding gene on chromosome 11q23.1, encoding Serine/threonine-protein kinase SIK2 (Q9H0K1). Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism.

Enables ATP binding activity; magnesium ion binding activity; and protein kinase activity. Involved in intracellular signal transduction and protein autophosphorylation. Is active in endoplasmic reticulum membrane.

Source: NCBI Gene 23235 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 13 total
• Druggable target: yes — 49 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21680
Approved symbol	SIK2
Name	salt inducible kinase 2
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0781, QIK, DKFZp434K1115, LOH11CR1I
Ensembl gene	ENSG00000170145
Ensembl biotype	protein_coding
OMIM	608973
Entrez	23235

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000304987, ENST00000533868, ENST00000876569, ENST00000876570, ENST00000940048

RefSeq mRNA: 1 — MANE Select: NM_015191 NM_015191

CCDS: CCDS8347

Canonical transcript exons

ENST00000304987 — 15 exons

Exon	Start	End
ENSE00000446324	111704987	111705139
ENSE00000989876	111688001	111688162
ENSE00000989877	111700886	111701010
ENSE00000989878	111701452	111701575
ENSE00000989880	111712211	111712375
ENSE00000989882	111720478	111720762
ENSE00000989883	111720899	111721062
ENSE00000989884	111721830	111721940
ENSE00000989885	111722665	111722756
ENSE00001154009	111703203	111703423
ENSE00001185069	111620339	111620402
ENSE00001185074	111616243	111616359
ENSE00001185079	111602449	111602698
ENSE00001302014	111723496	111730855
ENSE00003654923	111719775	111720003

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 93.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1622 / max 654.8848, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116631	18.9728	1795
206443	0.1284	62
116630	0.0611	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	93.14	gold quality
cardia of stomach	UBERON:0001162	91.38	gold quality
germinal epithelium of ovary	UBERON:0001304	90.86	gold quality
adipose tissue	UBERON:0001013	90.73	gold quality
lower lobe of lung	UBERON:0008949	90.57	gold quality
hair follicle	UBERON:0002073	90.50	silver quality
subcutaneous adipose tissue	UBERON:0002190	90.49	gold quality
stromal cell of endometrium	CL:0002255	90.40	gold quality
connective tissue	UBERON:0002384	90.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.26	gold quality
synovial joint	UBERON:0002217	90.16	gold quality
parietal lobe	UBERON:0001872	89.86	gold quality
islet of Langerhans	UBERON:0000006	89.83	gold quality
pericardium	UBERON:0002407	89.64	gold quality
vena cava	UBERON:0004087	89.64	gold quality
postcentral gyrus	UBERON:0002581	89.52	gold quality
superficial temporal artery	UBERON:0001614	89.44	gold quality
CA1 field of hippocampus	UBERON:0003881	89.40	gold quality
superior vestibular nucleus	UBERON:0007227	89.35	gold quality
endothelial cell	CL:0000115	89.19	gold quality
ventral tegmental area	UBERON:0002691	89.17	gold quality
pylorus	UBERON:0001166	89.15	gold quality
orbitofrontal cortex	UBERON:0004167	89.07	gold quality
parietal pleura	UBERON:0002400	89.00	gold quality
gastrocnemius	UBERON:0001388	88.86	gold quality
cartilage tissue	UBERON:0002418	88.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.58	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, KAT7

miRNA regulators (miRDB)

119 targeting SIK2, 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-188-3P	100.00	68.76	1240
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 39)

• Increased SIK2 expression is associated with diffuse large B-cell lymphoma. (PMID:20367563)
• Depletion of SIK2 also delayed G1/S transition and reduced AKT phosphorylation. Higher expression of SIK2 significantly correlated with poor survival in patients with high-grade serous ovarian cancers (PMID:20708153)
• In adipocytes, Ser358 (not Ser587) is the main site phosphorylated and responsible for the binding of SIK2 to 14-3-3 proteins. (PMID:22462548)
• findings uncover SIK2 as a critical determinant in autophagy progression and further suggest a mechanism in which the interplay among kinase and deacetylase activities contributes to cellular protein pool homeostasis. (PMID:23322770)
• tumor suppressor kinase LKB1 activates the downstream kinases SIK2 and SIK3 to stimulate nuclear export of class IIa histone deacetylases (PMID:23393134)
• These findings revealed a new function of LKB1 and salt-inducible kinases as negative regulators of HTLV-1 transcription. (PMID:23577667)
• a mechanism by which the interplay between SIK2 and p97/VCP contributes to the regulation of ERAD in mammalian cells. (PMID:24129571)
• this study suggests that the tightly linked regulatory loop comprised of the SIK2-PP2A and CaMKI and PME-1 networks may function in fine-tuning cell proliferation and stress response. (PMID:24841198)
• Examination of SIK2 in prostate cancer cells found that it functions both as a positive regulator of cell-cycle progression and a negative regulator of CREB1 activity. Also, the study shows high levels of auto-antibodies against SIK2 in plasma. (PMID:25548099)
• salt-inducible kinase inhibition decreases proinflammatory cytokines in human myeloid cells upon IL-1R stimulation. (PMID:26590148)
• Data show that microRNA miR-203 and the salt-inducible kinase 2 (SIK2) are reverse expressed in colorectal tumors. (PMID:27236538)
• The results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by peritoneal dialysis solutions. (PMID:27441650)
• Activated SIK2 plays a dual role in augmenting AMPK-induced phosphorylation of acetyl-CoA carboxylase and in activating the PI3K/AKT pathway through p85alpha-S154 phosphorylation. These findings identify SIK2 at the apex of the adipocyte-induced signaling cascades in cancer cells. (PMID:27478041)
• Findings suggest that SIK2 restricts autophagic flux which in the claudin-low subtype is essential for viability of triple-negative breast cancer cells. (PMID:27697861)
• SIK2 controls osteocyte responses to parathyroid hormone. (PMID:27759007)
• Data demonstrate that SIK2 and SIK3 mRNA are downregulated in adipose tissue from obese individuals and that the expression is regulated by weight change. SIK2 is also negatively associated with in vivo insulin resistance (HOMA-IR), independently of BMI and age. (PMID:27807598)
• Data suggest that cAMP/protein kinase A-dependent phosphorylation of SIK1, SIK2, and SIK3 inhibits their catalytic activity by inducing 14-3-3 protein binding. (PMID:29211348)
• results of this study indicate that SIK2 expression can serve as a prognostic biomarker for EOC and that miR-874-3p and miR-874-5p have the potential to enhance clinical treatment of EOC (PMID:30004169)
• Parathyroid hormone can affect the osteogenesis process of adipose tissue stem cells by regulating SIK2 and Wnt4. (PMID:31235257)
• In ovarian cancer (OC) cells SIK2 upregulated the expression of HIF-1alpha by activating the PI3K/AKT signaling pathway, which directly upregulated the transcription of major glycolytic genes to promote glycolysis and promoted mitochondrial fission through phosphorylation of Drp1 at Ser616 site, which inhibited the mitochondrial oxidative phosphorylation. SIK2 promoted growth and metastasis of OC cells. (PMID:31639424)
• High-Throughput Implementation of the NanoBRET Target Engagement Intracellular Kinase Assay to Reveal Differential Compound Engagement by SIK2/3 Isoforms. (PMID:31849250)
• SIK2 enhances synthesis of fatty acid and cholesterol in ovarian cancer cells and tumor growth through PI3K/Akt signaling pathway. (PMID:31932581)
• Salt-inducible kinases (SIKs) regulate TGFbeta-mediated transcriptional and apoptotic responses. (PMID:31969556)
• Salt-inducible Kinases Are Critical Determinants of Female Fertility. (PMID:32343771)
• Tumor-suppressor Fbxw7 targets SIK2 for degradation to interfere with TORC2-AKT signaling in pancreatic cancer. (PMID:32437091)
• JUP/plakoglobin is regulated by salt-inducible kinase 2, and is required for insulin-induced signalling and glucose uptake in adipocytes. (PMID:32966883)
• SIK2 represses AKT/GSK3beta/beta-catenin signaling and suppresses gastric cancer by inhibiting autophagic degradation of protein phosphatases. (PMID:33128264)
• SIK2 orchestrates actin-dependent host response upon Salmonella infection. (PMID:33947818)
• SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA-deficient cells. (PMID:34058059)
• Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human beta cell proliferation. (PMID:34302056)
• Salt-inducible kinase 2 functions as a tumor suppressor in hepatocellular carcinoma. (PMID:34491613)
• Role of saltinducible kinase 2 in the malignant behavior and glycolysis of colorectal cancer cells. (PMID:34558647)
• LINC00662 facilitates osteosarcoma progression via sponging miR-103a-3p and regulating SIK2 expression. (PMID:34559955)
• SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/beta-catenin signaling. (PMID:35277657)
• SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK. (PMID:35278271)
• SIK2 protects against renal tubular injury and the progression of diabetic kidney disease. (PMID:36075517)
• Inhibiting eukaryotic initiation factor 5A (eIF5A) hypusination attenuated activation of the SIK2 (salt-inducible kinase 2)-p4E-BP1 pathway involved in ovarian cancer cell proliferation and migration. (PMID:37219665)
• Salt-inducible kinases are required for glucose uptake and insulin signaling in human adipocytes. (PMID:37608474)
• LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition. (PMID:37966164)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sik2b	ENSDARG00000062315
danio_rerio	sik2a	ENSDARG00000079618
mus_musculus	Sik2	ENSMUSG00000037112
rattus_norvegicus	Sik2	ENSRNOG00000043498
drosophila_melanogaster	Sik2	FBGN0025625
caenorhabditis_elegans		WBGENE00002210

Paralogs (17): NUAK1 (ENSG00000074590), PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), HUNK (ENSG00000142149), SIK1 (ENSG00000142178), BRSK1 (ENSG00000160469), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), NUAK2 (ENSG00000163545), SNRK (ENSG00000163788), MELK (ENSG00000165304), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203), TSSK1B (ENSG00000212122)

Protein

Protein identifiers

Serine/threonine-protein kinase SIK2 — Q9H0K1 (reviewed: Q9H0K1)

Alternative names: Qin-induced kinase, Salt-inducible kinase 2, Serine/threonine-protein kinase SNF1-like kinase 2

All UniProt accessions (1): Q9H0K1

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism. Phosphorylates ‘Ser-794’ of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators. Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity. In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL. Also plays a role in thymic T-cell development.

Subunit / interactions. Interacts with and phosphorylates TORC2/CRTC2.

Subcellular location. Cytoplasm. Endoplasmic reticulum membrane.

Post-translational modifications. Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylated at Thr-484 in response to insulin in adipocytes. Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6.

Activity regulation. Activated by phosphorylation on Thr-175.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

RefSeq proteins (1): NP_056006* (*=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
IPR015940	UBA	Domain
IPR017090	Ser/Thr_kinase_SIK1/2	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR034672	SIK	Domain
IPR057380	UBA_SIK1/2/3	Domain

Pfam: PF00069, PF23312

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): modified residue 6, sequence variant 5, compositionally biased region 4, region of interest 3, domain 2, binding site 2, mutagenesis site 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0K1-F1	58.68	0.29

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): 142 (proton acceptor)

Ligand- & substrate-binding residues (2): 26–34; 49

Post-translational modifications (6): 25, 53, 175, 484, 534, 587

Mutagenesis-validated functional residues (2):

Position	Phenotype
175	prevents phosphorylation and activation by stk11/lkb1 complex.
175	constitutively active.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): E2F_Q4, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, PAX4_01, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, AREB6_03, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CREBP1_Q2, TGACCTY_ERR1_Q2, MEF2_02, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, NKX61_01

GO Biological Process (6): protein phosphorylation (GO:0006468), intracellular signal transduction (GO:0035556), regulation of insulin receptor signaling pathway (GO:0046626), protein autophosphorylation (GO:0046777), lipid biosynthetic process (GO:0008610), ERAD pathway (GO:0036503)

GO Molecular Function (10): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), 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), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
signal transduction	1
insulin receptor signaling pathway	1
regulation of signal transduction	1
protein phosphorylation	1
lipid metabolic process	1
biosynthetic process	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIK2	CRTC2	Q53ET0	807
SIK2	CRTC3	Q6UUV7	805
SIK2	CREB1	P16220	726
SIK2	CRTC1	Q6UUV9	693
SIK2	TCL1B	O95988	547
SIK2	PJA2	O43164	541
SIK2	NUAK2	Q9H093	540
SIK2	NUAK1	O60285	517
SIK2	RCAN2	Q14206	497
SIK2	RCAN3	Q9UKA8	495
SIK2	TCL1A	P56279	491
SIK2	MARK1	Q9P0L2	483
SIK2	CDK5	Q00535	478
SIK2	SIK3	Q9Y2K2	473
SIK2	MAGI3	Q5TCQ9	457

IntAct

73 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
SIK1	GINS4	psi-mi:“MI:0914”(association)	0.800
PPP2R2C	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
SIK2	VCP	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
SIK2	CEP250	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
SIK2	CEP250	psi-mi:“MI:0915”(physical association)	0.620
CEP250	SIK2	psi-mi:“MI:0915”(physical association)	0.620
CEP250	SIK2	psi-mi:“MI:0403”(colocalization)	0.620
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
SIK2	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.560
GABARAPL2	SIK2	psi-mi:“MI:0915”(physical association)	0.560
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
PIK3R1	SIK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SIK2	ACACA	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SIK2	PIK3R1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	PIK3CA	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (149): SIK2 (Two-hybrid), BAG2 (Affinity Capture-MS), CSNK1A1 (Affinity Capture-MS), EMD (Affinity Capture-MS), FUS (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), SHROOM3 (Affinity Capture-MS), SLC25A1 (Affinity Capture-MS), SLC25A13 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), YWHAE (Affinity Capture-MS), SIK2 (Affinity Capture-MS), VCP (Affinity Capture-Western)

ESM2 similar proteins: A0A1W2PPF3, A0A3B3IT52, E9Q3T6, O02747, O13161, O42173, O57374, O73622, O95238, P01103, P01104, P09632, P0C7M4, P10242, P14837, P17278, P30561, P31538, P41738, P46200, Q1KKS8, Q28G02, Q32NH9, Q4JM65, Q5REX1, Q5WM45, Q66IG8, Q68EH7, Q6U8D7, Q6ZTZ1, Q7T1K4, Q8BIL2, Q8BKE5, Q8CFH6, Q8IWB6, Q8JIT7, Q8NHV9, Q8R4S2, Q8R4S4, Q8R4S5

Diamond homologs: A0AUV4, A1A5Q6, A2KF29, A2XFF4, A8WYE4, B2DD29, B7XHR6, B8BBT7, C0HKC8, C0HKC9, F1QGZ6, O08678, O08679, O22932, O22971, O65554, O74536, O94168, P27448, P52497, P54645, P54646, P57059, P92958, Q00372, Q02723, Q03141, Q05512, Q09137, Q0D4B2, Q0JI49, Q13131, Q19469, Q28948, Q2QY53, Q2RAX3, Q2V452, Q38997, Q54DF2, Q54TA3

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
STK11	up-regulates	SIK2	phosphorylation
SIK2	down-regulates	CRTC2	phosphorylation
SIK2	down-regulates	CEP250	phosphorylation
SIK2	unknown	CEP250	phosphorylation
SIK2	down-regulates	CDK5R1	phosphorylation
SIK2	“up-regulates activity”	LRP6	phosphorylation
SIK2	“down-regulates activity”	EP300	phosphorylation
SIK2	unknown	IRS1	phosphorylation
SIK2	down-regulates	MLXIPL
SIK2	“down-regulates quantity”	IRS1	phosphorylation
SIK2	“up-regulates activity”	SIK2	phosphorylation
SIK2	“up-regulates activity”	PIK3R1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Activation of BAD and translocation to mitochondria	6	93.2×	6e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	82.3×	7e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	82.3×	7e-09
Activation of BH3-only proteins	6	60.8×	5e-08
RHO GTPases activate PKNs	6	38.8×	7e-07
Intrinsic Pathway for Apoptosis	6	35.9×	1e-06
SARS-CoV-1-host interactions	6	21.5×	1e-05
Apoptosis	6	20.6×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	28.6×	5e-04
intracellular protein localization	7	11.4×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3359 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111602696:G:GT	donor_gain	1.0000
11:111616233:T:TA	acceptor_gain	1.0000
11:111616234:G:A	acceptor_gain	1.0000
11:111616238:TGCA:T	acceptor_loss	1.0000
11:111616239:GCAG:G	acceptor_loss	1.0000
11:111616240:CA:C	acceptor_loss	1.0000
11:111616241:A:AC	acceptor_loss	1.0000
11:111616242:G:A	acceptor_loss	1.0000
11:111616355:ATCAG:A	donor_loss	1.0000
11:111616356:TCAG:T	donor_loss	1.0000
11:111616357:CAG:C	donor_loss	1.0000
11:111616358:AGG:A	donor_loss	1.0000
11:111616359:GGT:G	donor_loss	1.0000
11:111616360:GT:G	donor_loss	1.0000
11:111616361:T:A	donor_loss	1.0000
11:111620666:G:GT	donor_gain	1.0000
11:111684029:TGA:T	donor_gain	1.0000
11:111684031:A:T	donor_gain	1.0000
11:111687993:A:AG	acceptor_gain	1.0000
11:111687994:T:G	acceptor_gain	1.0000
11:111687995:TTACA:T	acceptor_loss	1.0000
11:111687997:ACAG:A	acceptor_loss	1.0000
11:111687999:A:AG	acceptor_gain	1.0000
11:111687999:AGAC:A	acceptor_loss	1.0000
11:111688000:G:GG	acceptor_gain	1.0000
11:111688000:GA:G	acceptor_gain	1.0000
11:111688000:GAC:G	acceptor_gain	1.0000
11:111688000:GACT:G	acceptor_gain	1.0000
11:111688000:GACTA:G	acceptor_gain	1.0000
11:111699989:GGA:G	donor_gain	1.0000

AlphaMissense

6067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:111602615:G:A	G18R	1.000
11:111602615:G:C	G18R	1.000
11:111602615:G:T	G18W	1.000
11:111602616:G:A	G18E	1.000
11:111602642:G:C	G27R	1.000
11:111602643:G:A	G27D	1.000
11:111602643:G:T	G27V	1.000
11:111602648:G:A	G29S	1.000
11:111602648:G:C	G29R	1.000
11:111602648:G:T	G29C	1.000
11:111602649:G:A	G29D	1.000
11:111602649:G:C	G29A	1.000
11:111602649:G:T	G29V	1.000
11:111602654:T:A	F31I	1.000
11:111602654:T:C	F31L	1.000
11:111602655:T:C	F31S	1.000
11:111602655:T:G	F31C	1.000
11:111602656:C:A	F31L	1.000
11:111602656:C:G	F31L	1.000
11:111602657:G:C	A32P	1.000
11:111602658:C:A	A32D	1.000
11:111602664:T:A	V34E	1.000
11:111602666:A:G	K35E	1.000
11:111602668:G:C	K35N	1.000
11:111602668:G:T	K35N	1.000
11:111602672:G:T	G37W	1.000
11:111602673:G:A	G37E	1.000
11:111602679:A:G	H39R	1.000
11:111616246:G:C	A47P	1.000
11:111616247:C:A	A47E	1.000

dbSNP variants (sampled 300 via entrez): RS1000007272 (11:111689554 A>G), RS1000050820 (11:111641713 C>T), RS1000065784 (11:111634767 C>T), RS1000070943 (11:111713438 A>G), RS1000106835 (11:111729644 T>C), RS1000114466 (11:111662187 G>A), RS1000118265 (11:111616737 T>A), RS1000204960 (11:111608070 G>A), RS1000249193 (11:111662529 G>A,T), RS1000310396 (11:111678217 C>A), RS1000315840 (11:111608279 A>G), RS1000317262 (11:111641283 C>T), RS1000329252 (11:111705541 C>T), RS1000354998 (11:111685315 C>T), RS1000363487 (11:111685691 ATAT>A)

Disease associations

OMIM: gene MIM:608973 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST004030_7	Primary sclerosing cholangitis	5.000000e-07
GCST005038_73	Allergic disease (asthma, hay fever or eczema)	7.000000e-15
GCST006627_13	Diastolic blood pressure	2.000000e-10
GCST006670_10	Primary sclerosing cholangitis	3.000000e-09
GCST007563_14	Allergic disease (asthma, hay fever or eczema)	1.000000e-10
GCST007564_5	Asthma or allergic disease (pleiotropy)	6.000000e-11
GCST007798_134	Asthma	2.000000e-09
GCST007799_31	Asthma (adult onset)	6.000000e-09
GCST007930_125	Medication use (agents acting on the renin-angiotensin system)	2.000000e-12
GCST008916_78	Asthma	2.000000e-08
GCST009524_214	Household income (MTAG)	8.000000e-09
GCST009720_54	Asthma	5.000000e-13
GCST010042_58	Asthma	1.000000e-10
GCST010043_52	Asthma	2.000000e-09
GCST010135_36	Oily fish consumption	9.000000e-09
GCST010140_26	Pork consumption	9.000000e-09
GCST010142_27	Fish- and plant-related diet	3.000000e-09
GCST010173_176	Triglyceride levels	3.000000e-08
GCST010703_266	Brain morphology (MOSTest)	4.000000e-13
GCST90002382_395	Eosinophil percentage of white cells	6.000000e-12
GCST90014325_50	Asthma	2.000000e-08
GCST90020024_418	A body shape index	1.000000e-11
GCST90020024_421	A body shape index	2.000000e-09
GCST90020025_874	Waist-to-hip ratio adjusted for BMI	3.000000e-10
GCST90020027_1627	Waist-hip index	5.000000e-11
GCST90020029_244	Waist circumference adjusted for body mass index	9.000000e-12
GCST90020029_246	Waist circumference adjusted for body mass index	8.000000e-15
GCST90020029_247	Waist circumference adjusted for body mass index	5.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:1002011	adult onset asthma
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009695	household income
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5699 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

49 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 471,872 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL2386889	SCH-900776	2
CHEMBL253969	OSI-632	2
CHEMBL3545396	BMS-690514	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — QIK subfamily

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
GLPG3970	Inhibition	11.0	pIC50
GLPG3312	Inhibition	9.15	pIC50
PF-07899895	Inhibition	9.05	pIC50
ARN-3236	Inhibition	9.0	pIC50
dasatinib	Inhibition	8.52	pIC50
bosutinib	Inhibition	8.52	pIC50
HG-9-91-01	Inhibition	8.18	pIC50

Binding affinities (BindingDB)

28 measured of 31 human assays (31 total across all organisms); most potent 28 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20250340556, Compound SLT-048	IC50	0.6 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
US20250340556, Compound SLT-073	IC50	0.7 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
US20250340556, Compound SLT-033	IC50	0.8 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
US20250340556, Compound SLT-062	IC50	0.8 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
US20250340556, Compound SLT-038	IC50	1 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
US20250340556, Compound SLT-079	IC50	1 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
Staurosporine	KD	1.7 nM
US20250340556, Compound SLT-061	IC50	2 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
US20250340556, Compound SLT-070	IC50	2 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
HG-9-91-01 derivative, 2	EC50	3 nM
US20250340556, Compound SLT-071	IC50	3 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
YKL-05-095 (3)	EC50	11 nM
US20250340556, Compound SLT-068	IC50	17 nM	US-20250340556: PYRIMIDOPYRIMIDONE COMPOUNDS AND METHODS OF USE THEREOF
BMS-354825	KD	27 nM
YKL-05-096 (4)	EC50	70 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
HG-9-91-01 (1)	EC50	220 nM
YKL-05-099 (5)	EC50	460 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 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
CI-1033	KD	1700 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 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

303 potent at pChembl≥5 of 307 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.72	IC50	0.019	nM	CHEMBL6148877
10.10	IC50	0.08	nM	CHEMBL6159758
9.52	IC50	0.3	nM	CHEMBL5090394
9.51	IC50	0.306	nM	STAUROSPORINE
9.46	IC50	0.345	nM	STAUROSPORINE
9.43	IC50	0.37	nM	STAUROSPORINE
9.40	IC50	0.4	nM	CHEMBL5407103
9.32	IC50	0.48	nM	CHEMBL6160074
9.30	IC50	0.5	nM	CHEMBL6146175
9.22	IC50	0.6	nM	CHEMBL5394880
9.22	IC50	0.6	nM	CHEMBL4553284
9.21	IC50	0.61	nM	CHEMBL5430450
9.20	Ki	0.631	nM	CHEMBL1980995
9.19	IC50	0.64	nM	CHEMBL5426204
9.15	IC50	0.7	nM	CHEMBL5394880
9.15	IC50	0.7	nM	CHEMBL5417444
9.10	Ki	0.7943	nM	DASATINIB
9.08	IC50	0.83	nM	CHEMBL6144245
9.05	IC50	0.9	nM	CHEMBL5438171
9.00	IC50	1	nM	CHEMBL4539742
9.00	Ki	1	nM	CHEMBL1993661
8.96	EC50	1.1	nM	STAUROSPORINE
8.96	Kd	1.1	nM	STAUROSPORINE
8.96	IC50	1.1	nM	CHEMBL6162015
8.80	IC50	1.6	nM	CHEMBL5440720
8.72	IC50	1.9	nM	CHEMBL5421558
8.72	IC50	1.9	nM	CHEMBL5405960
8.70	Kd	2	nM	CHEMBL400402
8.70	IC50	2	nM	CHEMBL4859969
8.66	IC50	2.2	nM	CHEMBL6161140
8.64	IC50	2.3	nM	CHEMBL5405960
8.64	IC50	2.3	nM	CHEMBL5431938
8.62	IC50	2.4	nM	CHEMBL5427025
8.60	IC50	2.5	nM	CHEMBL5412961
8.59	IC50	2.6	nM	CHEMBL5405883
8.57	IC50	2.7	nM	CHEMBL6172249
8.52	Kd	3	nM	CHEMBL4576489
8.52	IC50	3	nM	DASATINIB
8.48	IC50	3.3	nM	CHEMBL5404502
8.48	IC50	3.3	nM	CHEMBL5415380
8.41	IC50	3.9	nM	CHEMBL5397288
8.40	IC50	4	nM	CHEMBL3780091
8.40	Kd	4	nM	CHEMBL4465866
8.36	IC50	4.4	nM	CHEMBL3770443
8.32	IC50	4.8	nM	CHEMBL5437300
8.31	IC50	4.9	nM	CHEMBL6164789
8.31	IC50	4.9	nM	CHEMBL6143750
8.30	IC50	5	nM	CHEMBL6152906
8.28	IC50	5.3	nM	CHEMBL5420653
8.28	IC50	5.3	nM	CHEMBL5410472

PubChem BioAssay actives

249 with measured affinity, of 832 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
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(3-fluoro-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1895141: Inhibition of GST-tagged human SIK2 autophosphorylation measured after 30 mins in presence of [gamma33P]ATP by Western blot analysis	ic50	0.0003	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	1715171: Inhibition of human SIK2 using AMARAASAAALARRR as substrate by [gamma-33P]-ATP assay	ic50	0.0003	uM
2-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-5-ethyl-1,3,4-oxadiazole	1985480: Inhibition of SIK2 (unknown origin)	ic50	0.0004	uM
8-methoxy-6-[2-[[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]amino]-1,3-thiazol-5-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0006	uM
6-[2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazol-5-yl]-8-methoxy-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0006	uM
2-[8-methoxy-6-[2-[[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]amino]-1,3-thiazol-5-yl]-1-oxo-3,4-dihydroisoquinolin-2-yl]acetonitrile	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0006	uM
1-(2,4-dimethoxyphenyl)-3-(2,6-dimethylphenyl)-1-[6-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]urea	1992912: Inhibition of GST fused recombinant SIK2 (unknown origin) expressed in HEK293 cells ALNRTSSDSALHRRR as substrate incubated for 1 hr in presence of ATP	ic50	0.0006	uM
N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0007	uM
4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxybenzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0009	uM
3-(2,4-dimethoxyphenyl)-4-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridine	1895089: Inhibition of SIK2 (unknown origin)	ic50	0.0010	uM
3-(3,5-difluoro-2-methoxyphenyl)-5-(1-piperidin-4-ylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	1985480: Inhibition of SIK2 (unknown origin)	ic50	0.0010	uM
N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-[2-(oxan-4-yl)ethoxy]imidazo[1,2-a]pyridin-3-yl]benzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0016	uM
N-[5-[2-cyano-5-(1-methylazetidin-3-yl)oxy-4-pyridinyl]pyrazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide	1985480: Inhibition of SIK2 (unknown origin)	ic50	0.0019	uM
8-methoxy-6-[2-[(2-methyl-6-morpholin-4-ylpyrimidin-4-yl)amino]-1,3-thiazol-5-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0019	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425166: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0020	uM
2-(difluoromethoxy)-N-ethyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-6-methoxybenzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0023	uM
[4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxyphenyl]methanol	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0024	uM
N-cyclopropyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxybenzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0025	uM
N-cyclopropyl-2-(difluoromethoxy)-4-[7-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-6-methoxybenzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0026	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	2017518: Inhibition of SIK2 (unknown origin)	ic50	0.0030	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526255: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged SIK2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0030	uM
Bosutinib	2017518: Inhibition of SIK2 (unknown origin)	ic50	0.0030	uM
4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0033	uM
2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0033	uM
4-[5-[1-(cyanomethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-ethyl-2,6-dimethoxybenzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0039	uM
4-[(4-aminocyclohexyl)amino]-3-(1H-benzimidazol-2-yl)-1H-pyridin-2-one	1287937: Inhibition of SNF1LK2 (unknown origin)	ic50	0.0040	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526255: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged SIK2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0040	uM
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1895141: Inhibition of GST-tagged human SIK2 autophosphorylation measured after 30 mins in presence of [gamma33P]ATP by Western blot analysis	ic50	0.0044	uM
N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]benzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0048	uM
N-cyclopropyl-2-(difluoromethoxy)-4-[7-[4-(2-hydroxyethyl)piperazin-1-yl]imidazo[1,2-a]pyridin-3-yl]-6-methoxybenzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0053	uM
8-methoxy-6-[2-[[4-(morpholin-4-ylmethyl)-2-pyridinyl]amino]-1,3-thiazol-5-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0053	uM
N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl]benzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0054	uM
N-cyclopropyl-4-[7-(3,3-difluoroazetidin-1-yl)imidazo[1,2-a]pyridin-3-yl]-2-(difluoromethoxy)-6-methoxybenzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0057	uM
4-[2-(butylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1185905: Inhibition of QIK (unknown origin) by Off-chip Mobility Shift Assay	ic50	0.0057	uM
4-[7-(4-acetylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopropyl-2-(difluoromethoxy)-6-methoxybenzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0059	uM
3-(2-chloro-6-methylphenyl)-1-(5-methoxy-2-pyridinyl)-7-[4-(4-methylpiperazin-1-yl)anilino]-4H-pyrimido[4,5-d]pyrimidin-2-one	1801917: Caliper-based Mobility Shift Assay from Article 10.1021/acschembio.6b00217: “Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo.”	ic50	0.0060	uM
4-(cyclopropylamino)-N-(2-fluoro-6-methylphenyl)-2-[3-fluoro-4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	2017518: Inhibition of SIK2 (unknown origin)	ic50	0.0060	uM
4-[[2-[[5-[8-methoxy-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-6-yl]-1,3-thiazol-2-yl]amino]-4-pyridinyl]methyl]morpholin-3-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0064	uM
6-[2-[[6-[2-(dimethylamino)ethoxy]-2-pyridinyl]amino]-1,3-thiazol-5-yl]-8-methoxy-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0066	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1425166: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0070	uM
8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0078	uM
8-methoxy-6-[2-[(4-morpholin-4-yl-2-pyridinyl)amino]-1,3-thiazol-5-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one	1975694: Inhibition of SIK2 (unknown origin) using AMARA as substrate buffer incubated for 60 mins followed by addition of ADP-Glo reagent further incubated for 60 mins	ic50	0.0078	uM
N-ethyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxybenzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0079	uM
4-(cyclobutylamino)-N-(2-fluoro-6-methylphenyl)-2-[3-fluoro-4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	2017518: Inhibition of SIK2 (unknown origin)	ic50	0.0080	uM
N-ethyl-2,6-dimethoxy-4-[5-[1-(oxan-4-yl)pyrazol-4-yl]benzimidazol-1-yl]benzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0092	uM
N-cyclopropyl-2-(difluoromethoxy)-4-[7-[3-(dimethylamino)azetidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-6-methoxybenzamide	1985483: Inhibition of full length human SIK2 using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0101	uM
4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-methylbenzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0105	uM
(2S,3R,4R,6R,18S)-18-hydroxy-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	1425166: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0110	uM
N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1425166: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0110	uM
N-ethyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide	1992749: Inhibition of SIK2 (unknown origin) using AMARA peptide as substrate incubated for 120 mins in presence of ATP by ADP-Glo assay	ic50	0.0112	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	increases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation, affects cotreatment	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Quercetin	decreases phosphorylation	1
Rifampin	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Zinc	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

259 unique, capped per target: 258 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043815	Binding	Residual activity of SNF1LK2 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1963784	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SIK2	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TL13	HAP1 SIK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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