STK16

gene
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Also known as MPSK1PKL12MPSK

Summary

STK16 (serine/threonine kinase 16, HGNC:11394) is a protein-coding gene on chromosome 2q35, encoding Serine/threonine-protein kinase 16 (O75716). Membrane-associated protein kinase that phosphorylates on serine and threonine residues.

Predicted to enable protein serine/threonine kinase activity. Involved in protein autophosphorylation. Located in cytosol; nuclear body; and plasma membrane.

Source: NCBI Gene 8576 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 60 total — 1 likely-pathogenic
  • Druggable target: yes — 35 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001330213

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11394
Approved symbolSTK16
Nameserine/threonine kinase 16
Location2q35
Locus typegene with protein product
StatusApproved
AliasesMPSK1, PKL12, MPSK
Ensembl geneENSG00000115661
Ensembl biotypeprotein_coding
OMIM604719
Entrez8576

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000396738, ENST00000409260, ENST00000409516, ENST00000409638, ENST00000409743, ENST00000461417, ENST00000475342, ENST00000475696, ENST00000478018, ENST00000486813, ENST00000491697, ENST00000496443, ENST00000496800, ENST00000875262, ENST00000875263, ENST00000875264, ENST00000875265, ENST00000913739, ENST00000913740, ENST00000913741

RefSeq mRNA: 4 — MANE Select: NM_001330213 NM_001008910, NM_001330213, NM_001330214, NM_001330215

CCDS: CCDS42822, CCDS82573, CCDS86921

Canonical transcript exons

ENST00000396738 — 8 exons

ExonStartEnd
ENSE00001811654219245479219245796
ENSE00001819845219248421219250337
ENSE00003522107219247415219247535
ENSE00003575220219248193219248314
ENSE00003606757219245896219246085
ENSE00003624428219247113219247246
ENSE00003684484219246657219246876
ENSE00003692589219247662219247757

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 93.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5476 / max 133.8733, expressed in 1808 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
2543315.54761808

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499193.11gold quality
body of pancreasUBERON:000115092.73gold quality
right lobe of liverUBERON:000111492.72gold quality
right adrenal gland cortexUBERON:003582792.20gold quality
islet of LangerhansUBERON:000000692.18gold quality
olfactory segment of nasal mucosaUBERON:000538692.12gold quality
granulocyteCL:000009492.00gold quality
right adrenal glandUBERON:000123391.99gold quality
stromal cell of endometriumCL:000225591.93gold quality
body of stomachUBERON:000116191.85gold quality
left adrenal gland cortexUBERON:003582591.50gold quality
left adrenal glandUBERON:000123491.40gold quality
right testisUBERON:000453491.38gold quality
left testisUBERON:000453391.34gold quality
right lobe of thyroid glandUBERON:000111990.92gold quality
transverse colonUBERON:000115790.80gold quality
left lobe of thyroid glandUBERON:000112090.57gold quality
lower esophagus mucosaUBERON:003583490.55gold quality
adenohypophysisUBERON:000219690.43gold quality
metanephros cortexUBERON:001053390.41gold quality
apex of heartUBERON:000209890.19gold quality
rectumUBERON:000105290.14gold quality
minor salivary glandUBERON:000183090.02gold quality
pancreasUBERON:000126489.93gold quality
small intestine Peyer’s patchUBERON:000345489.76gold quality
prefrontal cortexUBERON:000045189.75gold quality
lower esophagusUBERON:001347389.72gold quality
lower esophagus muscularis layerUBERON:003583389.72gold quality
gall bladderUBERON:000211089.66gold quality
esophagogastric junction muscularis propriaUBERON:003584189.42gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes3.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting STK16, 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-4476100.0068.182030
HSA-MIR-6876-5P100.0067.682126
HSA-MIR-1252-5P100.0069.802774
HSA-MIR-6888-3P99.9765.951170
HSA-MIR-807599.9767.20962
HSA-MIR-589-3P99.9169.622088
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-1343-3P99.8966.781815
HSA-MIR-132199.8465.301811
HSA-MIR-473999.8465.251832
HSA-MIR-4756-5P99.8464.981809
HSA-MIR-465899.7764.94514
HSA-MIR-6790-5P99.7765.24505
HSA-MIR-197699.7465.481127
HSA-MIR-4755-5P99.7170.342716
HSA-MIR-5006-3P99.7170.262728
HSA-MIR-365999.7067.97694
HSA-MIR-64699.6867.841645
HSA-MIR-5004-5P99.6866.631294
HSA-MIR-29899.6367.561916
HSA-MIR-4743-3P99.6268.122095
HSA-MIR-1249-5P99.6166.552049
HSA-MIR-6797-5P99.6166.552084
HSA-MIR-7106-5P99.5367.473574
HSA-MIR-444199.4966.563216
HSA-MIR-143-3P99.4969.051457
HSA-MIR-477099.4969.091451
HSA-MIR-1224-5P99.4865.59803
HSA-MIR-127599.4767.902749
HSA-MIR-516A-3P99.4667.961378

Literature-anchored findings (GeneRIF, showing 6)

  • The Endogenous STK16 subcellular localization was evaluated by indirect immunofluorescence in NRK cells, demonstrating a Golgi-associated pattern that appears to be independent of signals provided by integrin pathways. (PMID:16310770)
  • MAL2 and STK16 function to sort secretory soluble cargo into the constitutive secretory pathway in hepatocytes. (PMID:25084525)
  • we revealed STK16 as a novel actin binding protein that resides in the Golgi, which regulates actin dynamics to control Golgi structure and participate in cell cycle progression. (PMID:28294156)
  • Exosomes from M1-polarized macrophages promote apoptosis in lung adenocarcinoma via the miR-181a-5p/ETS1/STK16 axis. (PMID:35092121)
  • STK16 promoted colorectal cancer progress in a c-MYC signaling-dependent manner. (PMID:38622518)
  • Serine/Threonine kinase 16 phosphorylates STAT3 and confers a JAK2-Inhibition resistance phenotype in triple-negative breast cancer. (PMID:38723720)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriostk16ENSDARG00000037777
mus_musculusStk16ENSMUSG00000026201
rattus_norvegicusStk16ENSRNOG00000019294
drosophila_melanogasterCG1227FBGN0037491

Paralogs (2): AAK1 (ENSG00000115977), BMP2K (ENSG00000138756)

Protein

Protein identifiers

Serine/threonine-protein kinase 16O75716 (reviewed: O75716)

Alternative names: Myristoylated and palmitoylated serine/threonine-protein kinase, Protein kinase PKL12, TGF-beta-stimulated factor 1, Tyrosine-protein kinase STK16, hPSK

All UniProt accessions (4): B4DPS1, O75716, B8ZZI5, B8ZZN3

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. Also autophosphorylates. May be involved in secretory vesicle trafficking or intracellular signaling. May have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. May be involved in TGF-beta signaling. Able to autophosphorylate on Tyr residue; it is however unclear whether it has tyrosine-protein kinase toward other proteins.

Subunit / interactions. Monomer. Interacts with DRG1 (via its N-terminal); the interaction phosphorylates DRG1.

Subcellular location. Cytoplasm. Perinuclear region. Membrane.

Tissue specificity. Ubiquitously expressed at very low levels.

Post-translational modifications. Mainly autophosphorylated on serine/threonine residues. Also autophosphorylated on Tyr-198. It is uncertain whether palmitoylation is on Cys-6 and/or Cys-8.

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

RefSeq proteins (4): NP_001008910, NP_001317142, NP_001317143, NP_001317144 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR008271Ser/Thr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR052239Ser/Thr-specific_kinasesFamily

Pfam: PF00069

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

SubstrateKm (mM)Measurements
ATP0.0007–0.6411
KKRAARATSNVFA0.013–0.0453
PAH1 PHOSPHATIDATE PHOSPHATASE0.00022
RRRLSSLRA0.0036–0.00372
GTP0.461
KKRAARASSNVFA0.021
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA0.00931
MYELIN BASIC PROTEIN0.1451

Catalyzed reactions (Rhea), 3 shown:

  • L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
  • 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 (52 total): helix 13, strand 11, sequence variant 5, sequence conflict 5, lipid moiety-binding region 3, mutagenesis site 3, modified residue 3, turn 2, binding site 2, initiator methionine 1, chain 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
2BUJX-RAY DIFFRACTION2.6

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O75716-F193.410.88

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): 148 (proton acceptor)

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

Post-translational modifications (6): 2, 6, 8, 185, 197, 198

Mutagenesis-validated functional residues (3):

PositionPhenotype
2loss of myristoylation.
6loss of palmitoylation.
8loss of palmitoylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOCC_GOLGI_ASSOCIATED_VESICLE, CREB_Q2_01, GOBP_RESPONSE_TO_GROWTH_FACTOR, USF_02, HAMAI_APOPTOSIS_VIA_TRAIL_DN, GOBP_PROTEIN_AUTOPHOSPHORYLATION, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_NON_MEMBRANE_SPANNING_PROTEIN_TYROSINE_KINASE_ACTIVITY, TCANNTGAY_SREBP1_01, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_ADENYL_NUCLEOTIDE_BINDING

GO Biological Process (4): positive regulation of transcription by RNA polymerase II (GO:0045944), protein autophosphorylation (GO:0046777), cellular response to transforming growth factor beta stimulus (GO:0071560), protein phosphorylation (GO:0006468)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), protein serine/threonine kinase activity (GO:0004674), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), Golgi-associated vesicle (GO:0005798), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure5
protein kinase activity3
cytoplasm3
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
positive regulation of DNA-templated transcription1
protein phosphorylation1
cellular response to growth factor stimulus1
response to transforming growth factor beta1
phosphorylation1
protein modification process1
RNA polymerase II transcription regulatory region sequence-specific DNA binding1
cis-regulatory region sequence-specific DNA binding1
protein tyrosine kinase activity1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
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
intracellular anatomical structure1
endomembrane system1
intracellular membrane-bounded organelle1
cytoplasmic vesicle1
membrane1
cell periphery1
nucleoplasm1
intracellular membraneless organelle1

Protein interactions and networks

STRING

1105 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
STK16NPPCP23582651
STK16UGT2B7P16662548
STK16DRG1Q9Y295526
STK16GCKP35557491
STK16CSNK1G1Q9HCP0467
STK16HNF1AP20823455
STK16FOXH1O75593434
STK16LHX3Q9UBR4426
STK16SERPINE1P05121424
STK16SRSF1Q07955400
STK16RIOK1Q9BRS2393
STK16GATA5Q9BWX5389
STK16ACIN1Q9UKV3389
STK16PCBD1P61457386
STK16SLCO1A2P46721384

IntAct

435 interactions, top by confidence:

ABTypeScore
STK16KCTD17psi-mi:“MI:0915”(physical association)0.780
KCTD17STK16psi-mi:“MI:0915”(physical association)0.780
TRIM42STK16psi-mi:“MI:0915”(physical association)0.720
SAXO1STK16psi-mi:“MI:0915”(physical association)0.720
EFEMP2STK16psi-mi:“MI:0915”(physical association)0.720
KRTAP10-8STK16psi-mi:“MI:0915”(physical association)0.720
INCA1STK16psi-mi:“MI:0915”(physical association)0.720
STK16PLSCR3psi-mi:“MI:0915”(physical association)0.720
STK16EFEMP2psi-mi:“MI:0915”(physical association)0.720
STK16KRTAP10-8psi-mi:“MI:0915”(physical association)0.720
STK16INCA1psi-mi:“MI:0915”(physical association)0.720
PLSCR3STK16psi-mi:“MI:0915”(physical association)0.720
RPIASTK16psi-mi:“MI:0915”(physical association)0.670
MIIPSTK16psi-mi:“MI:0915”(physical association)0.670
KCTD14STK16psi-mi:“MI:0915”(physical association)0.670
STK16MIIPpsi-mi:“MI:0915”(physical association)0.670
STK16KCTD14psi-mi:“MI:0915”(physical association)0.670
STK16RPIApsi-mi:“MI:0915”(physical association)0.670

BioGRID (182): STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), STK16 (Two-hybrid), DNAJA3 (Two-hybrid), CALCOCO2 (Two-hybrid)

ESM2 similar proteins: A0A5B9GBF0, A1CPG7, A1D2C9, A1IVT7, A2BD05, A2QRF6, B0XR80, D3ZBE5, G1XJZ4, G5EDF7, G5EFM9, M1T7M3, O09110, O75716, O88697, P0CP69, P21708, P26696, P27361, P28482, P45985, P46196, P46734, P47809, P52564, P57760, P59895, P70236, Q0D0P5, Q0U4L8, Q1DUU8, Q1KTF2, Q2WFL5, Q4PC06, Q4W6D3, Q4WSF6, Q52PH6, Q56R42, Q5E9X2, Q63844

Diamond homologs: A0QNG1, A5D791, A5GFW1, A5TY84, A5U3A3, A5U3A6, A8XJQ6, B0BBT2, O14965, O75716, P0A5S5, P0DPS8, P0DPS9, P18652, P33973, P38070, P41808, P53599, P53739, P54666, P54737, P54744, P57760, P57993, P59241, P9WI70, P9WI71, P9WI74, P9WI75, P9WI76, P9WI77, P9WI78, P9WI79, P9WI80, P9WI81, Q04J43, Q0WPH8, Q255D2, Q2TA06, Q3KM61

SIGNOR signaling

4 interactions.

AEffectBMechanism
STK16unknownSTK16phosphorylation
STK16unknownDRG1phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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:

PathwayPartnersFoldFDR
Keratinization1012.7×1e-06

GO biological processes:

GO termPartnersFoldFDR
negative regulation of gene expression77.8×1e-02
protein phosphorylation77.7×1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic1
Uncertain significance47
Likely benign1
Benign1

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
2578200NM_006000.3(TUBA4A):c.313C>T (p.Arg105Cys)Likely pathogenic

SpliceAI

1346 predictions. Top by Δscore:

VariantEffectΔscore
2:219245891:TCCA:Tacceptor_loss1.0000
2:219245894:A:ACacceptor_loss1.0000
2:219245894:A:AGacceptor_gain1.0000
2:219245894:AGCAT:Aacceptor_gain1.0000
2:219245895:G:GGacceptor_gain1.0000
2:219245895:GC:Gacceptor_gain1.0000
2:219245895:GCA:Gacceptor_gain1.0000
2:219245895:GCAT:Gacceptor_gain1.0000
2:219245895:GCATG:Gacceptor_gain1.0000
2:219246049:A:AGdonor_gain1.0000
2:219246081:GAGGG:Gdonor_gain1.0000
2:219246083:GGG:Gdonor_gain1.0000
2:219246084:GGG:Gdonor_gain1.0000
2:219246647:T:TAacceptor_gain1.0000
2:219246655:A:AGacceptor_gain1.0000
2:219246655:AGT:Aacceptor_gain1.0000
2:219246655:AGTG:Aacceptor_gain1.0000
2:219246656:G:GGacceptor_gain1.0000
2:219246656:GT:Gacceptor_gain1.0000
2:219246656:GTG:Gacceptor_gain1.0000
2:219246656:GTGG:Gacceptor_gain1.0000
2:219246835:GGTGC:Gdonor_gain1.0000
2:219246836:GTGC:Gdonor_gain1.0000
2:219246837:TGCT:Tdonor_gain1.0000
2:219247411:ACAG:Aacceptor_loss1.0000
2:219247412:CA:Cacceptor_loss1.0000
2:219247413:A:AGacceptor_gain1.0000
2:219247413:AG:Aacceptor_loss1.0000
2:219247414:G:GGacceptor_gain1.0000
2:219247414:G:GTacceptor_loss1.0000

AlphaMissense

2001 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
2:219246717:G:CK49N1.000
2:219246717:G:TK49N1.000
2:219246661:T:CF31L0.999
2:219246663:C:AF31L0.999
2:219246663:C:GF31L0.999
2:219247417:A:CD148A0.999
2:219247417:A:TD148V0.999
2:219247418:C:AD148E0.999
2:219247418:C:GD148E0.999
2:219247424:G:CK150N0.999
2:219247424:G:TK150N0.999
2:219247435:T:AI154K0.999
2:219247471:A:TD166V0.999
2:219247472:C:AD166E0.999
2:219247472:C:GD166E0.999
2:219247696:G:CR199P0.999
2:219247755:T:AW219R0.999
2:219247755:T:CW219R0.999
2:219248479:C:AR280S0.999
2:219246713:T:CL48P0.998
2:219246715:A:GK49E0.998
2:219246716:A:TK49M0.998
2:219247417:A:GD148G0.998
2:219247422:A:GK150E0.998
2:219247433:T:AN153K0.998
2:219247433:T:GN153K0.998
2:219247471:A:CD166A0.998
2:219247684:C:TT195I0.998
2:219247708:T:CL203P0.998
2:219248200:G:AG222D0.998

dbSNP variants (sampled 300 via entrez): RS1000543493 (2:219245719 T>A,G), RS1001526126 (2:219247436 A>G), RS1002031647 (2:219246041 C>G,T), RS1002200789 (2:219245260 C>G), RS1003527769 (2:219250272 A>G), RS1003768201 (2:219247832 T>C), RS1003784936 (2:219243539 A>C), RS1003968493 (2:219250021 ACTC>A), RS1004033258 (2:219248897 G>A,T), RS1004510956 (2:219249095 G>C), RS1004566261 (2:219244287 C>T), RS1005329205 (2:219243734 T>C), RS1005497649 (2:219249706 A>T), RS1005798711 (2:219249979 G>A,C), RS1006116968 (2:219250269 G>A)

Disease associations

OMIM: gene MIM:604719 | disease phenotypes: MIM:616208, MIM:621226

GenCC curated gene-disease

Mondo (2): amyotrophic lateral sclerosis type 22 (MONDO:0014531), spastic ataxia 11, autosomal dominant (MONDO:0979230)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

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

GWAS associations

4 associations (top):

StudyTraitp-value
GCST90002385_463High light scatter reticulocyte count2.000000e-11
GCST90002386_534High light scatter reticulocyte percentage of red cells2.000000e-12
GCST90002405_4Reticulocyte count1.000000e-10
GCST90002406_71Reticulocyte fraction of red cells4.000000e-12

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0007986reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3938 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 188,381 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1078178MOMELOTINIB43,481
CHEMBL1287853FEDRATINIB43,554
CHEMBL1289926AXITINIB415,732
CHEMBL1789941RUXOLITINIB411,547
CHEMBL189963PALBOCICLIB413,102
CHEMBL2035187PACRITINIB43,345
CHEMBL2103830FOSTAMATINIB43,841
CHEMBL3301610ABEMACICLIB47,045
CHEMBL3301622GILTERITINIB42,395
CHEMBL3622821UPADACITINIB42,726
CHEMBL477772PAZOPANIB415,540
CHEMBL502835NINTEDANIB48,545
CHEMBL535SUNITINIB479,020
CHEMBL608533MIDOSTAURIN47,259
CHEMBL300138ENZASTAURIN33,209
CHEMBL3137331DEFACTINIB31,229
CHEMBL522892DOVITINIB34,944
CHEMBL603469LESTAURTINIB3
CHEMBL1721885SU-0148132363
CHEMBL230011TG100-11521,504
CHEMBL402548DANUSERTIB2
CHEMBL475251R-4062
CHEMBL482968ENMD-20762
CHEMBL495727AT-92832
CHEMBL513909BI-25362
CHEMBL521851PICTILISIB2
CHEMBL564829MILCICLIB2
CHEMBL572878TOZASERTIB2
CHEMBL1084546PF-005622711
CHEMBL1908397KW-24491

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — NAK family

Most potent curated ligand interactions (3 total), top 3:

LigandActionAffinityParameter
compound 13 [PMID: 34333981]Inhibition7.09pIC50
compound 6 [PMID: 34333981]Inhibition7.06pIC50
STK16-IN-1Inhibition6.53pIC50

Binding affinities (BindingDB)

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

LigandMeasureValue
StaurosporineKD1.7 nM
PKC-412KD190 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamideKD1100 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamideKD2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3bKD3100 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-carboxamideKD3500 nM
STK16-IN-1IC507940 nM

ChEMBL bioactivities

105 potent at pChembl≥5 of 109 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.77Kd1.7nMR-406
8.18Kd6.6nMFEDRATINIB
7.96Kd11nMCHEMBL5633837
7.78Kd16.67nMCHEMBL5653589
7.75Kd18nMCHEMBL1908395
7.75Kd18nMNINTEDANIB
7.72Kd19nMLESTAURTINIB
7.63ED5023.15nMCHEMBL5653589
7.62Kd24nMCHEMBL516312
7.54Kd29nMKW-2449
7.11Ki78nMCHEMBL4571548
7.09IC5082nMCHEMBL5079149
7.07Ki86nMCHEMBL4470026
7.06IC5088nMCHEMBL5083125
7.04Ki91nMCHEMBL4534959
7.03Kd93.93nMCHEMBL3752910
7.02Kd95nMR-406
6.97IC50107nMCHEMBL4877883
6.96Kd110nMCHEMBL4576489
6.96Ki110nMCHEMBL4552310
6.88ED50130.4nMCHEMBL3752910
6.86Kd138nMPF-00562271
6.85Kd140nMJNJ-7706621
6.83IC50148nMCHEMBL5437375
6.82Ki150nMCHEMBL4542463
6.78IC50167nMCHEMBL187139
6.75Ki180nMCHEMBL4447403
6.75Ki180nMCHEMBL4582326
6.73Kd186nMCHEMBL3688339
6.70Kd200nMSTAUROSPORINE
6.68Kd210nMCYC-116
6.66Ki220nMCHEMBL4472438
6.64Kd230nMCHEMBL1082152
6.63IC50235nMSTAUROSPORINE
6.62Ki240nMCHEMBL4535040
6.62IC50242nMSTAUROSPORINE
6.62IC50241nMSTAUROSPORINE
6.60Kd250nMSUNITINIB
6.57Ki270nMCHEMBL4452939
6.57Kd270nMSTAUROSPORINE
6.55Kd280nMMIDOSTAURIN
6.54Ki290nMCHEMBL4561238
6.53Kd295nMGILTERITINIB
6.51Ki310nMCHEMBL4531680
6.48Ki330nMCHEMBL4516665
6.46Ki350nMCHEMBL4452360
6.44Kd360nMSUNITINIB
6.44Kd365nMCHEMBL4465866
6.44Kd360nMPAZOPANIB
6.43Kd370nMAXITINIB

PubChem BioAssay actives

99 with measured affinity, of 836 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
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one624775: Binding constant for STK16 kinase domainkd0.0017uM
Fedratinib624775: Binding constant for STK16 kinase domainkd0.0066uM
2-[2-methyl-5-[3-(3,4,5-trimethoxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]anilino]ethanol2137777: Binding affinity to human STK16 assessed as dissociation constant by Adp-glo assaykd0.0110uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149509: Binding affinity to human STK16 incubated for 45 mins by Kinobead based pull down assaykd0.0167uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate624775: Binding constant for STK16 kinase domainkd0.0180uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride624775: Binding constant for STK16 kinase domainkd0.0180uM
(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-one508094: Binding affinity to STK16kd0.0190uM
N-[5-(4-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide389039: Binding affinity to human MPSK1kd0.0240uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone624775: Binding constant for STK16 kinase domainkd0.0290uM
N-[6-[3-(2-methylpropylsulfonylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.0780uM
N-[3-[[5-bromo-4-[(4-sulfamoylphenyl)methylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide1823769: Inhibition of human STK16 in presence of [gamma-33P-ATP] by radiometric scintillation assayic500.0820uM
N-[6-[3-[[[ethyl(methyl)sulfamoyl]amino]methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.0860uM
4-[[[5-bromo-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]methyl]benzenesulfonamide1823769: Inhibition of human STK16 in presence of [gamma-33P-ATP] by radiometric scintillation assayic500.0880uM
N-[6-[3-(cyclopropylmethylsulfonylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.0910uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149509: Binding affinity to human STK16 incubated for 45 mins by Kinobead based pull down assaykd0.0939uM
8-[3-chloro-5-(1-methylindazol-5-yl)-2H-pyrazolo[3,4-b]pyridin-4-yl]-2,8-diazaspiro[4.5]decan-1-one1769454: Inhibition of human wild type partial length STK16 (G11 to I305) expressed in bacterial expression system by Kinomescan methodic500.1070uM
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]propanamide1526317: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK16 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.1100uM
N-[6-[3-(propylsulfonylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.1100uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide1425179: 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.kd0.1380uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide435692: Binding constant for STK16 kinase domainkd0.1400uM
2-[5-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]-2-methylphenyl]-1H-benzimidazole-4-carboxamide1972173: Inhibition of MPSK1 (unknown origin) by Z’-Lyte kinase assayic500.1480uM
N-[6-[3-[(cyclopropylmethylsulfonylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.1500uM
N-[6-[3-[(3,3,3-trifluoropropylsulfonylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.1800uM
N-[6-[3-[(2,2,2-trifluoroethylsulfonylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.1800uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone1425179: 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.kd0.1860uM
(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-one256606: Average Binding Constant for STK16; NA=Not Active at 10 uMkd0.2000uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine1425179: 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.kd0.2100uM
N-[6-[3-[(diethylsulfamoylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.2200uM
3-[3-(2,3-dihydroxypropylamino)phenyl]-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione465274: Inhibition of STK16kd0.2300uM
N-[6-[3-(cyclobutylsulfonylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.2400uM
Sunitinib435692: Binding constant for STK16 kinase domainkd0.2500uM
N-[6-[3-(diethylsulfamoylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.2700uM
Midostaurin435692: Binding constant for STK16 kinase domainkd0.2800uM
N-[6-[3-[[[methyl(2,2,2-trifluoroethyl)sulfamoyl]amino]methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.2900uM
1-(4-fluoro-3-hydroxyphenyl)-7H-pyrrolo[2,3-h][1,6]naphthyridin-2-one1801714: Invitrogen SelectScreen Enzymatic Assay from Article 10.1021/acschembio.6b00250: “Discovery of a Highly Selective STK16 Kinase Inhibitor.”ic500.2950uM
Gilteritinib1425179: 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.kd0.2950uM
N-[6-[3-[[ethyl(methyl)sulfamoyl]amino]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.3100uM
N-[6-[3-(cyclopropylsulfonylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.3300uM
N-[6-[3-(dimethylsulfamoylamino)phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.3500uM
Pazopanib435692: Binding constant for STK16 kinase domainkd0.3600uM
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]propanamide1526317: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK16 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.3650uM
Axitinib624775: Binding constant for STK16 kinase domainkd0.3700uM
N-[6-[3-[(4-fluorophenyl)methylsulfonylamino]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.4300uM
N-[6-[3-[(2-methylpropylsulfonylamino)methyl]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.4500uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone769493: Binding affinity to STK16 (unknown origin)kd0.4500uM
N-[6-[3-[(2-fluorophenyl)methylsulfonylamino]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.4700uM
Ruxolitinib624775: Binding constant for STK16 kinase domainkd0.4900uM
Abemaciclib1425179: 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.kd0.4950uM
N-[6-[3-[(3-fluorophenyl)methylsulfonylamino]phenyl]-1H-indazol-3-yl]cyclopropanecarboxamide1547796: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged STK16 kinase domain (13 to 305 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assayki0.5100uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one256606: Average Binding Constant for STK16; NA=Not Active at 10 uMkd0.5100uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arseniteaffects expression, decreases expression2
Air Pollutantsaffects cotreatment, increases abundance, increases oxidation, increases expression2
Smokedecreases expression, increases abundance, increases expression2
Cadmium Chlorideincreases expression, decreases expression, increases abundance2
GSK-J4decreases expression1
methylmercuric chloridedecreases expression1
triphenyl phosphateaffects expression1
alpha-pineneaffects cotreatment, increases oxidation, increases abundance1
bisphenol Adecreases expression, increases methylation1
beta-lapachoneincreases expression1
nickel sulfateincreases expression1
methacrylaldehydeaffects cotreatment, increases oxidation, increases abundance1
CGP 52608affects binding, increases reaction1
abrineincreases expression1
jinfukangincreases expression1
Sunitinibdecreases expression1
Arsenic Trioxidedecreases response to substance1
Acroleinincreases oxidation, increases abundance, affects cotreatment1
Amiodaroneincreases expression1
Atrazineincreases expression1
Cadmiumincreases abundance, increases expression1
Leadaffects expression1
Ozoneaffects cotreatment, increases oxidation, increases abundance1
Quercetinincreases expression1
Tetrachlorodibenzodioxinaffects expression1
Okadaic Aciddecreases expression1
Volatile Organic Compoundsaffects cotreatment, increases oxidation1

ChEMBL screening assays

244 unique, capped per target: 244 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1020555BindingInhibition of STK16 assessed as enzyme activity relative to controlExamining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Cellosaurus cell lines

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

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

CellosaurusNameCategorySex
CVCL_B3IFAbcam HEK293T STK16 KOTransformed cell lineFemale
CVCL_TQ73HAP1 STK16 (-) 1Cancer cell lineMale
CVCL_TQ74HAP1 STK16 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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