STK10

gene
On this page

Also known as LOKPRO2729

Summary

STK10 (serine/threonine kinase 10, HGNC:11388) is a protein-coding gene on chromosome 5q35.1, encoding Serine/threonine-protein kinase 10 (O94804). Serine/threonine-protein kinase involved in regulation of lymphocyte migration.

This gene encodes a member of the Ste20 family of serine/threonine protein kinases, and is similar to several known polo-like kinase kinases. The protein can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. The kinase can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway.

Source: NCBI Gene 6793 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 171 total
  • Druggable target: yes — 79 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_005990

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11388
Approved symbolSTK10
Nameserine/threonine kinase 10
Location5q35.1
Locus typegene with protein product
StatusApproved
AliasesLOK, PRO2729
Ensembl geneENSG00000072786
Ensembl biotypeprotein_coding
OMIM603919
Entrez6793

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 10 protein_coding, 8 retained_intron, 6 protein_coding_CDS_not_defined

ENST00000176763, ENST00000517360, ENST00000517381, ENST00000517524, ENST00000517527, ENST00000517775, ENST00000518267, ENST00000519269, ENST00000519441, ENST00000519710, ENST00000520476, ENST00000521322, ENST00000522879, ENST00000522936, ENST00000523603, ENST00000523615, ENST00000877786, ENST00000877787, ENST00000877788, ENST00000877789, ENST00000877790, ENST00000916144, ENST00000916145, ENST00000916146

RefSeq mRNA: 1 — MANE Select: NM_005990 NM_005990

CCDS: CCDS34290

Canonical transcript exons

ENST00000176763 — 19 exons

ExonStartEnd
ENSE00000769446172156624172156788
ENSE00000812846172187887172188224
ENSE00000973051172096426172096560
ENSE00000973052172093412172093960
ENSE00000973055172082326172082505
ENSE00000973060172055588172055776
ENSE00000973061172054569172054694
ENSE00000973062172052929172053042
ENSE00001003610172064720172064812
ENSE00001003619172061139172061268
ENSE00001003620172042079172045022
ENSE00001507187172082961172083084
ENSE00001507188172090232172090362
ENSE00003484309172106620172106814
ENSE00003494266172107780172107852
ENSE00003494555172117481172117630
ENSE00003560084172057349172057473
ENSE00003589902172127373172127421
ENSE00003645837172105656172105737

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.9293 / max 1085.8611, expressed in 1794 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
6485421.01841778
648554.64421414
648533.76601062
648520.3482142
648410.058220
648560.058113
648420.036211

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
granulocyteCL:000009498.83gold quality
sural nerveUBERON:001548897.36gold quality
bloodUBERON:000017897.35gold quality
leukocyteCL:000073896.98gold quality
monocyteCL:000057696.93gold quality
mononuclear cellCL:000084296.88gold quality
spleenUBERON:000210696.01gold quality
cerebellar hemisphereUBERON:000224595.95gold quality
right hemisphere of cerebellumUBERON:001489095.80gold quality
cerebellar cortexUBERON:000212995.77gold quality
bone marrow cellCL:000209294.70gold quality
cerebellumUBERON:000203793.85gold quality
upper lobe of left lungUBERON:000895293.07gold quality
lymph nodeUBERON:000002992.94gold quality
vermiform appendixUBERON:000115492.55gold quality
upper lobe of lungUBERON:000894892.39gold quality
right lungUBERON:000216791.59gold quality
bone marrowUBERON:000237191.23gold quality
tibial nerveUBERON:000132391.20gold quality
omental fat padUBERON:001041490.80gold quality
peritoneumUBERON:000235890.73gold quality
adipose tissue of abdominal regionUBERON:000780890.07gold quality
left testisUBERON:000453390.00gold quality
right testisUBERON:000453489.81gold quality
skin of legUBERON:000151189.61gold quality
small intestine Peyer’s patchUBERON:000345489.37gold quality
bone elementUBERON:000147489.08gold quality
caecumUBERON:000115388.76gold quality
apex of heartUBERON:000209888.56gold quality
testisUBERON:000047388.30gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-MTAB-6678yes9.48
E-GEOD-110499no268.00
E-MTAB-6379no265.25
E-CURD-112no2.57
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting STK10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4283100.0066.422097
HSA-MIR-6867-5P100.0082.213464
HSA-MIR-5692A100.0074.406850
HSA-MIR-4692100.0067.322066
HSA-MIR-4682100.0068.891258
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-1252-5P100.0069.802774
HSA-MIR-451499.9967.101870
HSA-MIR-118499.9968.191458
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-548N99.9871.944170
HSA-MIR-56899.9869.862084
HSA-MIR-767-5P99.9570.85993
HSA-MIR-185-3P99.9567.011743
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-10527-5P99.9172.283754
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-95-5P99.8972.173973
HSA-MIR-1343-3P99.8966.781815
HSA-MIR-7162-3P99.8968.161682
HSA-MIR-3140-3P99.8868.472069
HSA-MIR-391999.8769.452489
HSA-MIR-548D-3P99.8770.674362
HSA-MIR-449299.8768.253611
HSA-MIR-548BB-3P99.8670.584354

Literature-anchored findings (GeneRIF, showing 9)

  • Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells (PMID:11903060)
  • Stk10 is a novel polo-like kinase kinase that cooperates with hSlk to regulate Plk1 function in human cells (PMID:12639966)
  • These studies identify a new ERM kinase of importance in lymphocytes and confirm the role of ezrin-radixin-moesin phosphorylation in regulating cell shape and motility. (PMID:19255442)
  • genetic polymorphism is associated with aspirin-intolerant asthma in a Korean population (PMID:21905501)
  • It was shown that lymphocyte-oriented and STE20 kinase were sufficient to restrict ezrin function to the apical domain. Both kinases were enriched in microvilli and locally activated there. (PMID:23209304)
  • STK10 functions as a tumor suppressor gene, and dysfunction of STK10 activity either through polymorphism or somatic mutations may confer anti-apoptotic effects contributing to carcinogenesis. (PMID:23842845)
  • The gene signature of OPA1, CTSA, NDUFA1, STK10 and PRDX1 was able to identify patients post-implant with a sensitivity of 91% and a specificity of 86% in discrimination between post-implant group and healthy controls. (PMID:27177495)
  • Binding of phosphatidylinositol 4,5-biphosphate to ezrin induces a conformational change permitting the insertion of the LOK C-terminal domain to wedge apart the membrane and F-actin-binding domains of ezrin. The N-terminal LOK kinase domain can then access a site 40 residues distal from the consensus sequence that collectively direct phosphorylation of the appropriate threonine residue. (PMID:28430576)
  • Systematic analysis of prognostic significance, functional enrichment and immune implication of STK10 in acute myeloid leukemia. (PMID:35501867)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriostk10ENSDARG00000101894
mus_musculusStk10ENSMUSG00000020272
rattus_norvegicusStk10ENSRNOG00000004217

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Serine/threonine-protein kinase 10O94804 (reviewed: O94804)

Alternative names: Lymphocyte-oriented kinase

All UniProt accessions (2): O94804, H0YB71

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.

Subunit / interactions. Homodimer; homodimerization is required for activation segment autophosphorylation.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in rapidly proliferating tissues (spleen, placenta, and peripheral blood leukocytes). Also expressed in brain, heart, skeletal muscle, colon, thymus, kidney, liver, small intestine and lung.

Post-translational modifications. Autophosphorylates following homodimerization, leading to activation of the protein.

Disease relevance. Testicular germ cell tumor (TGCT) [MIM:273300] A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by the pyrrole-indolinone inhibitor SU11274 (K00593): intercalates between the ATP-binding Lys-65 and alpha-C glutamate (Glu-81), resulting in a partial disordering of the lysine side chain. Also specifically inhibited by erlotinib. Slightly inhibited by gefitinib.

Miscellaneous. Inhibition by erlotinib, an orally administered EGFR tyrosine kinase inhibitor used for treatment, enhances STK10-dependent lymphocytic responses, possibly leading to the aggravation of skin inflammation observed upon treatment by erlotinib.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

RefSeq proteins (1): NP_005981* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR008271Ser/Thr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR022165PKKFamily
IPR042743STK10_STKcDomain
IPR051585STE20_Ser/Thr_KinasesFamily

Pfam: PF00069, PF12474

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 (72 total): helix 15, sequence variant 12, modified residue 10, strand 9, region of interest 7, turn 5, compositionally biased region 4, sequence conflict 3, binding site 2, chain 1, domain 1, active site 1, mutagenesis site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

14 structures.

PDBMethodResolution (Å)
6EIMX-RAY DIFFRACTION1.43
7QGPX-RAY DIFFRACTION1.9
2J7TX-RAY DIFFRACTION2
4EQUX-RAY DIFFRACTION2
6HXFX-RAY DIFFRACTION2.09
4BC6X-RAY DIFFRACTION2.2
5AJQX-RAY DIFFRACTION2.2
6GTTX-RAY DIFFRACTION2.25
5OWRX-RAY DIFFRACTION2.3
4AOTX-RAY DIFFRACTION2.33
6I2YX-RAY DIFFRACTION2.56
4USEX-RAY DIFFRACTION2.65
5OWQX-RAY DIFFRACTION2.7
4USDX-RAY DIFFRACTION3.05

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O94804-F174.820.50

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): 157 (proton acceptor)

Ligand- & substrate-binding residues (2): 42–50; 65

Post-translational modifications (10): 13, 20, 191, 438, 450, 454, 485, 514, 549, 952

Mutagenesis-validated functional residues (1):

PositionPhenotype
65loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

IDPathway
R-HSA-6798695Neutrophil degranulation
R-HSA-8980692RHOA GTPase cycle
R-HSA-9013026RHOB GTPase cycle
R-HSA-9013106RHOC GTPase cycle
R-HSA-162582Signal Transduction
R-HSA-168249Innate Immune System
R-HSA-168256Immune System
R-HSA-194315Signaling by Rho GTPases
R-HSA-9012999RHO GTPase cycle
R-HSA-9716542Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 312 (showing top): MODULE_97, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GNF2_CASP8, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, MODULE_182, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_CELL_CELL_ADHESION, GOBP_LEUKOCYTE_MIGRATION, FINETTI_BREAST_CANCER_KINOME_GREEN, XU_RESPONSE_TO_TRETINOIN_AND_NSC682994_UP

GO Biological Process (5): protein phosphorylation (GO:0006468), intracellular signal transduction (GO:0035556), protein autophosphorylation (GO:0046777), lymphocyte aggregation (GO:0071593), regulation of lymphocyte migration (GO:2000401)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), 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 (8): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

CategoryPathways
RHO GTPase cycle3
Innate Immune System1
Immune System1
Signaling by Rho GTPases, Miro GTPases and RHOBTB31
Signaling by Rho GTPases1
Signal Transduction1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
intracellular anatomical structure2
protein kinase activity2
phosphorylation1
protein modification process1
signal transduction1
protein phosphorylation1
leukocyte aggregation1
regulation of mononuclear cell migration1
lymphocyte migration1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
protein binding1
identical protein binding1
protein dimerization activity1
nucleoside phosphate binding1
heterocyclic compound binding1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
binding1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
nuclear lumen1
cytoplasm1
membrane1
cell periphery1
nucleoplasm1
intracellular membraneless organelle1
secretory granule membrane1
specific granule1
extracellular vesicle1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
STK10EZRP15311494
STK10MSNP26038464
STK10RDXP35241464
STK10RHOAP06749457
STK10PLK1P53350434
STK10IFNGP01579420
STK10ERBB2P04626397
STK10ERVMER34-1Q9H9K5355
STK10NHERF1O14745348
STK10C5orf52A6NGY3323
STK10UBTD2Q8WUN7311
STK10NR3C1P04150297
STK10NHERF2Q15599289
STK10ARHGEF37A1IGU5283
STK10ARHGEF38Q9NXL2279

IntAct

23 interactions, top by confidence:

ABTypeScore
CFTRESYT2psi-mi:“MI:2364”(proximity)0.710
STK10STK10psi-mi:“MI:0407”(direct interaction)0.620
MAP1LC3ASTK10psi-mi:“MI:0407”(direct interaction)0.440
STK10NONOpsi-mi:“MI:0915”(physical association)0.400
STK10psi-mi:“MI:0915”(physical association)0.400
Xpo1IFT56psi-mi:“MI:0914”(association)0.350
TANKCNOT1psi-mi:“MI:0914”(association)0.350
RIPK2CNOT1psi-mi:“MI:0914”(association)0.350
CAMK4CNOT1psi-mi:“MI:0914”(association)0.350
BORCS8SH3PXD2Bpsi-mi:“MI:0914”(association)0.350
TBC1D9SH3PXD2Bpsi-mi:“MI:0914”(association)0.350
MILR1SBNO1psi-mi:“MI:0914”(association)0.350
MRPL53psi-mi:“MI:0914”(association)0.350
TBKBP1psi-mi:“MI:0914”(association)0.350
PSMD12psi-mi:“MI:0914”(association)0.350
LAMP1PIPSLpsi-mi:“MI:2364”(proximity)0.270
CFTRUBA6psi-mi:“MI:2364”(proximity)0.270
CDH5ESYT2psi-mi:“MI:2364”(proximity)0.270

BioGRID (74): STK10 (Affinity Capture-RNA), STK10 (Affinity Capture-RNA), STK10 (Affinity Capture-RNA), STK10 (Affinity Capture-RNA), KIFC1 (Co-fractionation), STK10 (Affinity Capture-MS), STK10 (Affinity Capture-RNA), STK10 (Affinity Capture-RNA), STK10 (Affinity Capture-RNA), STK10 (Proximity Label-MS), STK10 (Proximity Label-MS), STK10 (Affinity Capture-RNA), STK10 (Affinity Capture-MS), STK10 (Affinity Capture-MS), NONO (Proximity Label-MS)

ESM2 similar proteins: A0JMA8, A5WW21, A8WVU9, B0S6J3, B7ZR30, E1BK52, E7F187, E9PTG8, F1NBT0, G5EFD2, O01583, O08815, O43150, O54874, O54988, O55092, O55098, O88664, O94804, P46549, Q08CX1, Q0IHQ8, Q22908, Q3UU96, Q4G3H4, Q53UA7, Q5F2E8, Q5R4F3, Q5U245, Q5VT25, Q5ZJB4, Q619T5, Q6DD27, Q6GPK9, Q6NU21, Q7L7X3, Q7SIG6, Q7SY52, Q7TT49, Q7TT50

Diamond homologs: A0A194VNL2, A0A1S4CGX4, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8XJW8, A9RWC9, A9S5R3, A9SR33, B0XPE4, C4YLK8, E1BK52, F1NBT0, G4N6Z6, G4NEB8, G5EDF7, O00506, O09110, O14733, O54748, O80396, O94804, O95819, P06784, P08018, P0CY25, P10506, P29678, P31938, P32490, P32491, P33886, P36506, P36507, P45985, P46734

SIGNOR signaling

2 interactions.

AEffectBMechanism
STK10“up-regulates activity”MSNphosphorylation
STK10“up-regulates activity”EZRphosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance136
Likely benign5
Benign5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3620 predictions. Top by Δscore:

VariantEffectΔscore
5:172045019:GAGC:Gacceptor_gain1.0000
5:172045020:AGC:Aacceptor_gain1.0000
5:172045020:AGCC:Aacceptor_loss1.0000
5:172045021:GC:Gacceptor_gain1.0000
5:172045022:CC:Cacceptor_gain1.0000
5:172045022:CCT:Cacceptor_loss1.0000
5:172045023:C:CCacceptor_gain1.0000
5:172045023:CTA:Cacceptor_loss1.0000
5:172052924:GTTA:Gdonor_loss1.0000
5:172052926:TAC:Tdonor_loss1.0000
5:172052928:CCTT:Cdonor_gain1.0000
5:172052931:T:Adonor_gain1.0000
5:172053039:CATT:Cacceptor_gain1.0000
5:172053041:TT:Tacceptor_gain1.0000
5:172053041:TTCTG:Tacceptor_loss1.0000
5:172053042:TCTGG:Tacceptor_loss1.0000
5:172053043:C:CCacceptor_gain1.0000
5:172053043:CTGGA:Cacceptor_loss1.0000
5:172053044:T:Gacceptor_loss1.0000
5:172053049:C:CTacceptor_gain1.0000
5:172053056:C:CTacceptor_gain1.0000
5:172053056:C:Tacceptor_gain1.0000
5:172054566:TA:Tdonor_loss1.0000
5:172054567:AC:Adonor_loss1.0000
5:172054568:C:CTdonor_loss1.0000
5:172054690:GAGAA:Gacceptor_gain1.0000
5:172054691:AGAA:Aacceptor_gain1.0000
5:172054692:GAA:Gacceptor_gain1.0000
5:172054693:AA:Aacceptor_gain1.0000
5:172054695:C:CCacceptor_gain1.0000

AlphaMissense

6454 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:172083073:A:GL566P1.000
5:172090325:C:GR531P1.000
5:172090326:G:TR531S1.000
5:172106674:A:TV245D1.000
5:172106728:A:GL227P1.000
5:172106740:A:GL223P1.000
5:172106745:C:AW221C1.000
5:172106745:C:GW221C1.000
5:172106747:A:GW221R1.000
5:172106747:A:TW221R1.000
5:172106753:C:GD219H1.000
5:172106797:A:TV204D1.000
5:172106812:A:CM199R1.000
5:172106812:A:GM199T1.000
5:172106812:A:TM199K1.000
5:172106814:C:AW198C1.000
5:172106814:C:GW198C1.000
5:172107781:A:GW198R1.000
5:172107781:A:TW198R1.000
5:172107784:A:CY197D1.000
5:172107784:A:GY197H1.000
5:172107786:G:TP196H1.000
5:172107792:C:TG194D1.000
5:172107793:C:GG194R1.000
5:172107797:G:CF192L1.000
5:172107797:G:TF192L1.000
5:172107799:A:GF192L1.000
5:172107844:C:GG177R1.000
5:172107848:G:CD175E1.000
5:172107848:G:TD175E1.000

dbSNP variants (sampled 300 via entrez): RS1000033992 (5:172142280 C>A), RS1000038065 (5:172056360 G>C), RS1000064835 (5:172133580 G>A), RS1000070058 (5:172177270 G>C), RS1000082564 (5:172095875 A>G), RS1000096966 (5:172133941 G>C), RS1000105369 (5:172061242 C>T), RS1000137865 (5:172061039 A>C,T), RS1000142524 (5:172145496 C>T), RS1000145432 (5:172098755 T>G), RS1000159789 (5:172173543 G>A,T), RS1000174272 (5:172055746 G>A), RS1000187145 (5:172136868 C>T), RS1000190220 (5:172101081 C>T), RS1000197703 (5:172108811 G>T)

Disease associations

OMIM: gene MIM:603919 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST006658_10Longevity9.000000e-06
GCST006979_480Heel bone mineral density2.000000e-11
GCST007202_15High density lipoprotein cholesterol levels6.000000e-06
GCST011066_4Motor fluctuations in levodopa treated Parkinson’s disease9.000000e-06
GCST011108_2Colorectal cancer x fine particulate matter exposure levels interaction2.000000e-09
GCST90002404_228Red cell distribution width2.000000e-21

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0009270heel bone mineral density
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0010747response to levodopa
EFO:0010749motor function measurement
EFO:0008255particulate matter air pollution measurement
EFO:0009188Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3981 (SINGLE PROTEIN), CHEMBL4888459 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

79 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 469,629 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1173655AFATINIB415,144
CHEMBL1287853FEDRATINIB43,554
CHEMBL1289494TIVOZANIB44,455
CHEMBL1289601LENVATINIB48,784
CHEMBL1289926AXITINIB415,732
CHEMBL1336SORAFENIB486,060
CHEMBL180022NERATINIB49,404
CHEMBL2035187PACRITINIB43,345
CHEMBL24828VANDETANIB442,230
CHEMBL255863NILOTINIB438,627
CHEMBL288441BOSUTINIB412,255
CHEMBL3301607FILGOTINIB42,905
CHEMBL3301610ABEMACICLIB47,045
CHEMBL3301622GILTERITINIB42,395
CHEMBL3545311BRIGATINIB45,634
CHEMBL477772PAZOPANIB415,540
CHEMBL502835NINTEDANIB48,545
CHEMBL535SUNITINIB479,020
CHEMBL5416410DASATINIB4655
CHEMBL553ERLOTINIB4108,300
CHEMBL554LAPATINIB4
CHEMBL576982QUIZARTINIB4
CHEMBL601719CRIZOTINIB4
CHEMBL608533MIDOSTAURIN4
CHEMBL939GEFITINIB4
CHEMBL2087361ICOTINIB3
CHEMBL2105728CRENOLANIB3
CHEMBL217092SARACATINIB3
CHEMBL223360LINIFANIB3
CHEMBL270995BRIVANIB ALANINATE3

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — SLK subfamily

Most potent curated ligand interactions (2 total), top 2:

LigandActionAffinityParameter
DDR1/2 inhibitor 5nInhibition8.0pKd
bosutinibInhibitor7.28pIC50

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
3-[2-(cyclopropanecarbonylamino)-[1,3]thiazolo[5,4-b]pyridin-5-yl]-N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamideKD57 nMUS-8765747: Fused 2-aminothiazole compounds

ChEMBL bioactivities

255 potent at pChembl≥5 of 265 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.52Kd0.03nMSTAUROSPORINE
10.43Kd0.037nMSTAUROSPORINE
9.28Kd0.53nMFORETINIB
9.04Kd0.92nMAST-487
8.52Kd3nMUCN-01
8.24Kd5.7nMLESTAURTINIB
8.23Kd5.9nMBAY-826
8.16IC506.93nMSTAUROSPORINE
8.15Kd7.1nMDORAMAPIMOD
8.15Kd7nMBOSUTINIB
8.04IC509.01nMSTAUROSPORINE
8.02Kd9.5nMCHEMBL2148124
8.00Kd10nMCHEMBL4168305
8.00Kd10nMCHEMBL4571241
7.92IC5012nMCHEMBL156277
7.92Kd12nMDORAMAPIMOD
7.89Kd13nMNERATINIB
7.89Kd13nMKW-2449
7.85Kd14nMCHEMBL3688339
7.81IC5015.6nMSTAUROSPORINE
7.72Kd19nMERLOTINIB
7.72Kd19nMSUNITINIB
7.66Kd22nMCHEMBL1908396
7.64IC5023nMCHEMBL4875188
7.64Kd23nMCEDIRANIB
7.58Ki26nMCHEMBL4875188
7.49Kd32.12nMCHEMBL5653589
7.46Ki35nMCHEMBL4878325
7.46ED5035.08nMCHEMBL5653589
7.36Kd44nMCRIZOTINIB
7.34Ki46nMCHEMBL156277
7.33Ki47nMCHEMBL4877889
7.33IC5047nMREBASTINIB
7.28IC5052nMBOSUTINIB
7.24Kd57nMCHEMBL5084426
7.22IC5060nMCHEMBL4878325
7.22Kd60nMRAF-265
7.21Ki61nMCHEMBL4856751
7.16Kd70nMR-406
7.16Kd69nMGSK-461364
7.15Kd71nMDECERNOTINIB
7.14Ki73nMCHEMBL157089
7.12Ki76nMCHEMBL4855513
7.11Kd77nMCHEMBL1241674
7.09Kd81nMVANDETANIB
7.09Kd82nMAT-9283
7.09Kd82nMTAE-684
7.08Kd83nMERLOTINIB
7.08Ki84nMCHEMBL4869745
7.08Kd84nMPAZOPANIB

PubChem BioAssay actives

247 with measured affinity, of 1298 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.

CompoundAssayTypeValueUnit
(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-one256604: Average Binding Constant for STK10; NA=Not Active at 10 uMkd<0.0001uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide625030: Binding constant for LOK kinase domainkd0.0005uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea435677: Binding constant for LOK kinase domainkd0.0009uM
(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-one1425177: 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.kd0.0030uM
(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-one507591: Binding affinity to LOKkd0.0057uM
3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide2155086: Binding affinity to LOK (unknown origin) assessed as dissociation constant by KINOME scan assaykd0.0059uM
Bosutinib625030: Binding constant for LOK kinase domainkd0.0070uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea256604: Average Binding Constant for STK10; NA=Not Active at 10 uMkd0.0071uM
N-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-3-fluorophenyl]-6-ethyl-1,2-dimethyl-4-oxoquinoline-3-carboxamide1626965: Binding affinity to human LOKkd0.0100uM
3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-ylbenzamide1356736: Binding affinity to human LOKkd0.0100uM
N-[3-[2-[4-(2-aminoethoxy)anilino]quinazolin-6-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide1799897: Fluorescence Assay from Article 10.1021/cb300623a: “A Hexylchloride-Based Catch-and-Release System for Chemical Proteomic Applications.”ic500.0100uM
3-(3-chloroanilino)-4-(2-methoxyphenyl)pyrrole-2,5-dione1779843: Inhibition of STK10 (unknown origin) expressed in Sf9 cells assessed as transfer of radiolabelled phosphate group from ATP by reaction biology methodic500.0120uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone625030: Binding constant for LOK kinase domainkd0.0130uM
Neratinib625030: Binding constant for LOK kinase domainkd0.0130uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone1425177: 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.kd0.0140uM
Erlotinib435677: Binding constant for LOK kinase domainkd0.0190uM
Sunitinib435677: Binding constant for LOK kinase domainkd0.0190uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea625030: Binding constant for LOK kinase domainkd0.0220uM
3-[[4-(2-methoxyphenyl)-2,5-dioxopyrrol-3-yl]amino]benzonitrile1779843: Inhibition of STK10 (unknown origin) expressed in Sf9 cells assessed as transfer of radiolabelled phosphate group from ATP by reaction biology methodic500.0230uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline625030: Binding constant for LOK kinase domainkd0.0230uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149507: Binding affinity to human STK10 incubated for 45 mins by Kinobead based pull down assaykd0.0321uM
3-[[4-(4-bromo-2-methoxyphenyl)-2,5-dioxopyrrol-3-yl]amino]benzonitrile1779840: Binding affinity human STK10 by binding displacement assayki0.0350uM
Crizotinib625030: Binding constant for LOK kinase domainkd0.0440uM
3-(2-methoxyphenyl)-4-(naphthalen-1-ylamino)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.0470uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide2168214: Inhibition of human LOK preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysisic500.0470uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine435677: Binding constant for LOK kinase domainkd0.0600uM
3-[[4-(5-bromo-2-methoxyphenyl)-2,5-dioxopyrrol-3-yl]amino]benzonitrile1779840: Binding affinity human STK10 by binding displacement assayki0.0610uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide625030: Binding constant for LOK kinase domainkd0.0690uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one625030: Binding constant for LOK kinase domainkd0.0700uM
(2R)-2-methyl-2-[[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]-N-(2,2,2-trifluoroethyl)butanamide1425177: 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.kd0.0710uM
3-(3-chloro-4-hydroxyanilino)-4-(2-methoxyphenyl)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.0730uM
3-(3-fluoroanilino)-4-(2-methoxyphenyl)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.0760uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol625030: Binding constant for LOK kinase domainkd0.0770uM
Vandetanib435677: Binding constant for LOK kinase domainkd0.0810uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea1425177: 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.kd0.0820uM
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-diamine625030: Binding constant for LOK kinase domainkd0.0820uM
Pazopanib435677: Binding constant for LOK kinase domainkd0.0840uM
3-(1,3-benzodioxol-5-ylamino)-4-(2-methoxyphenyl)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.0840uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate625030: Binding constant for LOK kinase domainkd0.0870uM
N-[4-[4-(3-cyanoanilino)-2,5-dioxopyrrol-3-yl]-3-methoxyphenyl]-2-methylpropanamide1779840: Binding affinity human STK10 by binding displacement assayki0.0880uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid1425177: 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.kd0.0960uM
3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propyl carbamimidothioate1779843: Inhibition of STK10 (unknown origin) expressed in Sf9 cells assessed as transfer of radiolabelled phosphate group from ATP by reaction biology methodic500.0990uM
3-(2-methoxyphenyl)-4-(3-methylsulfanylanilino)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.1100uM
3-(2-methoxyphenyl)-4-(quinolin-6-ylamino)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.1100uM
3-[(4-naphthalen-1-yl-2,5-dioxopyrrol-3-yl)amino]benzonitrile1779840: Binding affinity human STK10 by binding displacement assayki0.1100uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide435677: Binding constant for LOK kinase domainkd0.1100uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide256604: Average Binding Constant for STK10; NA=Not Active at 10 uMkd0.1100uM
3-(4-methoxyanilino)-4-(2-methoxyphenyl)pyrrole-2,5-dione1779840: Binding affinity human STK10 by binding displacement assayki0.1200uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide435677: Binding constant for LOK kinase domainkd0.1200uM
Brigatinib2182831: Inhibition of human STK10 using RLGRDKYKTLRQIRQ as substrate in presence of [gamma33P]-ATP by HotSpot assayic500.1230uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Tobacco Smoke Pollutiondecreases expression, increases expression, affects expression3
Benzo(a)pyreneaffects methylation, decreases expression2
Estradiolaffects cotreatment, increases expression2
aristolochic acid Iincreases expression1
FR900359decreases phosphorylation1
bisphenol Fincreases expression1
testosterone enanthateaffects expression1
triphenyl phosphateaffects expression1
arseniteaffects binding, decreases reaction1
sodium arseniteincreases expression1
benzo(e)pyreneincreases methylation1
potassium chromate(VI)affects cotreatment, decreases expression1
coumarinaffects phosphorylation1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediaminedecreases expression1
epigallocatechin gallateaffects cotreatment, decreases expression1
azoxystrobindecreases expression1
CGP 52608affects binding, increases reaction1
calfactantaffects cotreatment, decreases expression1
bisphenol Bincreases expression1
abrineincreases expression1
bisphenol Saffects cotreatment, increases methylation1
picoxystrobindecreases expression1
Sunitinibincreases expression1
Fulvestrantaffects cotreatment, increases methylation1
Acetaminophenincreases expression1
Aspirinaffects response to substance1
Caffeinedecreases phosphorylation1
Ethyl Methanesulfonateincreases expression1
Ivermectindecreases expression1
Methapyrileneincreases methylation1

ChEMBL screening assays

308 unique, capped per target: 308 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1004492BindingBinding affinity to human recombinant LOK expressed in Escherichia coli assessed as thermal shift by differential scanning fluorimetryDiscovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

CellosaurusNameCategorySex
CVCL_B2HMAbcam HeLa STK10 KOCancer cell lineFemale
CVCL_TQ69HAP1 STK10 (-) 1Cancer cell lineMale
CVCL_TQ70HAP1 STK10 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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