MAP3K10

Summary

MAP3K10 (mitogen-activated protein kinase kinase kinase 10, HGNC:6849) is a protein-coding gene on chromosome 19q13.2, encoding Mitogen-activated protein kinase kinase kinase 10 (Q02779). Activates the JUN N-terminal pathway.

The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis.

Source: NCBI Gene 4294 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 148 total
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002446

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6849
Approved symbol	MAP3K10
Name	mitogen-activated protein kinase kinase kinase 10
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MST, MEKK10
Ensembl gene	ENSG00000130758
Ensembl biotype	protein_coding
OMIM	600137
Entrez	4294

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000253055, ENST00000593502, ENST00000593906, ENST00000594569, ENST00000594791, ENST00000594951, ENST00000597986, ENST00000601702, ENST00000856942, ENST00000856945, ENST00000933473, ENST00000941194

RefSeq mRNA: 1 — MANE Select: NM_002446 NM_002446

CCDS: CCDS12549

Canonical transcript exons

ENST00000253055 — 10 exons

Exon	Start	End
ENSE00000706439	40198375	40198555
ENSE00000706442	40204485	40204633
ENSE00001139930	40214970	40215575
ENSE00001233426	40191426	40192713
ENSE00003459811	40205121	40205296
ENSE00003497961	40213076	40213188
ENSE00003506477	40209103	40209219
ENSE00003622117	40205911	40206157
ENSE00003627565	40213517	40214221
ENSE00003644900	40212805	40212976

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 96.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9490 / max 108.4932, expressed in 1732 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175818	4.0986	1614
175819	1.0781	614
175820	1.0665	519
175817	0.2957	100
175816	0.1561	65
175821	0.1305	61
175822	0.1235	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	96.75	gold quality
prefrontal cortex	UBERON:0000451	96.43	gold quality
cingulate cortex	UBERON:0003027	96.39	gold quality
anterior cingulate cortex	UBERON:0009835	96.34	gold quality
amygdala	UBERON:0001876	95.84	gold quality
type B pancreatic cell	CL:0000169	95.77	silver quality
nucleus accumbens	UBERON:0001882	95.05	gold quality
putamen	UBERON:0001874	94.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.51	gold quality
cortical plate	UBERON:0005343	94.40	gold quality
caudate nucleus	UBERON:0001873	94.09	gold quality
cerebellar hemisphere	UBERON:0002245	94.08	gold quality
cerebellar cortex	UBERON:0002129	94.07	gold quality
olfactory bulb	UBERON:0002264	93.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.25	gold quality
neocortex	UBERON:0001950	93.13	gold quality
frontal cortex	UBERON:0001870	93.12	gold quality
frontal lobe	UBERON:0016525	93.11	gold quality
cerebellum	UBERON:0002037	92.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.00	silver quality
telencephalon	UBERON:0001893	91.94	gold quality
triceps brachii	UBERON:0001509	91.43	gold quality
cerebral cortex	UBERON:0000956	91.40	gold quality
forebrain	UBERON:0001890	91.29	gold quality
diaphragm	UBERON:0001103	91.20	gold quality
brain	UBERON:0000955	91.12	gold quality
lateral globus pallidus	UBERON:0002476	91.06	silver quality
central nervous system	UBERON:0001017	91.00	gold quality
vena cava	UBERON:0004087	90.79	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF3

miRNA regulators (miRDB)

33 targeting MAP3K10, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-4732-3P	97.15	65.45	881

Literature-anchored findings (GeneRIF, showing 15)

• MLK2 has a role in vesicle formation and endosome recycling by binding to clathrin (PMID:12105200)
• demonstrate Alien-MLK2 interaction and also show that MLK2 is able to phosphorylate Alien; Alien, DAX-1 and thyroid hormone receptor mediated transcriptional silencing is strongly enhanced in the presence of active MLK2 (PMID:15062575)
• MLK2 and -3 are required for activation of JNK and p38 by ectopically expressed GCK (PMID:17584736)
• Hippocalcin and MLK2 were colocalized in the halo of Lewy bodies in Parkinson disease patients, and neither protein was detected in normal pigmented neurons. (PMID:19332348)
• Mixed lineage kinase phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways (PMID:19801649)
• Data show that miR-181b contributed to proliferation of AML cells by targeting MLK2. (PMID:20596961)
• This study showed that show that RUNX3 is a principal and evolutionarily conserved component of the MST pathway. (PMID:21678419)
• Mechanism of MAP kinase activation by TNF requires Src-dependent activation of Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site on MLK2 and 3. (PMID:21979919)
• Mechanism of MAP kinase activation by TNF requires Src-dependent activation of Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site on MLK3. (PMID:21979919)
• A novel and important role for MAP3K10 in the proliferation and chemoresistance of pancreatic ductal adenocarcinoma. (PMID:23178452)
• MAP3K4 is sufficiently mediate the TGFbeta-induced phosphorylation of p38 MAPK in MEFs and HaCaT cells. (PMID:23760366)
• We identified a direct target of miR-155 as MAP3K10 in osteosarcoma (PMID:28214207)
• MST interaction with MOB1 is not essential for development and tissue growth control. (PMID:28947795)
• DNA methylationregulated miR1555p depresses sensitivity of esophageal carcinoma cells to radiation and multiple chemotherapeutic drugs via suppression of MAP3K10. (PMID:32323857)
• DNA methylation of the MAP3K10 gene may participate in the development of intracranial aneurysm. (PMID:36341729)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	map3k10	ENSDARG00000055672
mus_musculus	Map3k10	ENSMUSG00000040390
rattus_norvegicus	Map3k10	ENSRNOG00000023521

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TESK1 (ENSG00000107140), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), RAF1 (ENSG00000132155), RIPK1 (ENSG00000137275), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), ILK (ENSG00000166333), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MOS (ENSG00000172680), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase 10 — Q02779 (reviewed: Q02779)

Alternative names: Mixed lineage kinase 2, Protein kinase MST

All UniProt accessions (4): Q02779, M0R0A7, M0R1J8, M0R365

UniProt curated annotations — full annotation on UniProt →

Function. Activates the JUN N-terminal pathway.

Subunit / interactions. Homodimer. Interacts with SH3RF2.

Tissue specificity. Expressed in brain and skeletal muscle.

Post-translational modifications. Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation.

Activity regulation. Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation.

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

RefSeq proteins (1): NP_002437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016231	MLK1-4	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR035779	MLK1-3_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051681	Ser/Thr_Kinases-Pseudokinases	Family

Pfam: PF07714, PF14604

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 (37 total): modified residue 7, compositionally biased region 6, sequence conflict 5, region of interest 5, strand 4, domain 2, binding site 2, sequence variant 2, helix 2, chain 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2RF0	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02779-F1	61.33	0.27

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): 222 (proton acceptor)

Ligand- & substrate-binding residues (2): 104–112; 125

Post-translational modifications (7): 258, 262, 498, 502, 506, 558, 857

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_JNK_CASCADE, DER_IFN_BETA_RESPONSE_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, BIOCARTA_MAPK_PATHWAY, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, KUUSELO_PANCREATIC_CANCER_19Q13_AMPLIFICATION, GOBP_SMOOTHENED_SIGNALING_PATHWAY

GO Biological Process (13): apoptotic process (GO:0006915), signal transduction (GO:0007165), smoothened signaling pathway (GO:0007224), JNK cascade (GO:0007254), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), positive regulation of apoptotic process (GO:0043065), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), positive regulation of JUN kinase activity (GO:0043507), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of JNK cascade (GO:0046330), protein autophosphorylation (GO:0046777), protein phosphorylation (GO:0006468)

GO Molecular Function (14): transcription corepressor activity (GO:0003714), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), JUN kinase kinase kinase activity (GO:0004706), ATP binding (GO:0005524), protein homodimerization activity (GO:0042803), bHLH transcription factor binding (GO:0043425), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), MAP kinase kinase kinase activity (GO:0004709), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein phosphorylation	3
protein kinase activity	3
MAPK cascade	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
peptidyl-serine modification	1
peptidyl-threonine modification	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
JUN kinase activity	1
positive regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
phosphorylation	1
protein modification process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
MAP kinase kinase kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
DNA-binding transcription factor binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

1712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP3K10	MAPK8IP2	Q13387	904
MAP3K10	KIF3A	Q9Y496	826
MAP3K10	MAPK8IP1	Q9UQF2	746
MAP3K10	CNKSR1	Q969H4	683
MAP3K10	CDC42	P21181	615
MAP3K10	MAPK8	P45983	518
MAP3K10	SMAD4	Q13485	477
MAP3K10	KLC2	Q9H0B6	450
MAP3K10	JUN	P05412	448
MAP3K10	KLC3	Q6P597	448
MAP3K10	KLC4	Q9NSK0	434
MAP3K10	KLC1	Q07866	433
MAP3K10	SLC2A2	P11168	423
MAP3K10	KIF17	Q9P2E2	415
MAP3K10	MAP2K7	O14733	405

IntAct

25 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
	MAP3K10	psi-mi:“MI:0407”(direct interaction)	0.440
MAP3K10	GARS1	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
AXL		psi-mi:“MI:0914”(association)	0.350
MAP3K10	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
MAP3K21	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
HPCA	ANKRD33B	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	PLEKHG3	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
ABL2	MAP3K10	psi-mi:“MI:0915”(physical association)	0.000
MAP3K21	MAP3K10	psi-mi:“MI:0915”(physical association)	0.000
LCOR	MAP3K10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (72): MAP2K4 (Biochemical Activity), KIFAP3 (Affinity Capture-Western), MAP3K10 (Two-hybrid), MAP3K10 (Biochemical Activity), POMC (Negative Genetic), SLC5A5 (Negative Genetic), MAPK12 (Negative Genetic), MAP3K10 (Negative Genetic), MAP3K10 (Negative Genetic), MAP3K10 (Negative Genetic), PRKCZ (Negative Genetic), MAP3K10 (Negative Genetic), TSPO (Negative Genetic), PIK3R2 (Negative Genetic), MAP3K10 (Negative Genetic)

ESM2 similar proteins: A0JPN4, A1YF56, A2A288, A2A9T0, A2AEV7, A6QQJ8, A7MCY6, A8MVW0, D3ZG83, D3ZZN9, O09039, O15037, O75427, O94983, O95382, O95947, P0C5W1, P98077, Q02779, Q16584, Q2M3V2, Q53LP3, Q5D1E7, Q5D1E8, Q66HA1, Q66K74, Q66L42, Q6DG50, Q6ZUM4, Q6ZW31, Q76KP1, Q7T0L4, Q7TSG2, Q80XI6, Q80Y50, Q8BIY3, Q8BLS7, Q8K120, Q8K1S6, Q8R5G7

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
MAPK8IP1	up-regulates	MAP3K10	binding
MAP3K10	down-regulates	TCF3	phosphorylation
MAP3K10	“up-regulates activity”	MAP2K4	phosphorylation
SH3RF1	up-regulates	MAP3K10	binding
MAP3K10	“up-regulates activity”	NEUROD1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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	7	355.3×	8e-16
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	313.5×	1e-15
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	313.5×	1e-15
Activation of BH3-only proteins	7	231.7×	1e-14
RHO GTPases activate PKNs	7	148.0×	3e-13
Intrinsic Pathway for Apoptosis	7	136.7×	5e-13
FOXO-mediated transcription	5	112.0×	4e-09
SARS-CoV-1-host interactions	7	82.0×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	107.8×	8e-08
intracellular protein localization	7	43.1×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	130
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2037 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40192711:ACA:A	donor_gain	1.0000
19:40192714:G:GG	donor_gain	1.0000
19:40198370:CACA:C	acceptor_loss	1.0000
19:40198371:ACAG:A	acceptor_loss	1.0000
19:40198372:C:G	acceptor_gain	1.0000
19:40198373:A:AC	acceptor_loss	1.0000
19:40198373:A:AG	acceptor_gain	1.0000
19:40198374:G:GT	acceptor_gain	1.0000
19:40198374:GT:G	acceptor_gain	1.0000
19:40198374:GTC:G	acceptor_gain	1.0000
19:40198374:GTCC:G	acceptor_gain	1.0000
19:40198374:GTCCT:G	acceptor_gain	1.0000
19:40198473:A:G	donor_gain	1.0000
19:40198509:G:GT	donor_gain	1.0000
19:40198540:GCA:G	donor_gain	1.0000
19:40198553:G:GT	donor_gain	1.0000
19:40198588:G:GT	donor_gain	1.0000
19:40198588:G:T	donor_gain	1.0000
19:40204483:A:AG	acceptor_gain	1.0000
19:40204484:G:GG	acceptor_gain	1.0000
19:40204484:GCT:G	acceptor_gain	1.0000
19:40204484:GCTTC:G	acceptor_gain	1.0000
19:40205117:CCAGA:C	acceptor_loss	1.0000
19:40205118:CA:C	acceptor_loss	1.0000
19:40205119:A:AG	acceptor_gain	1.0000
19:40205119:AGA:A	acceptor_loss	1.0000
19:40205120:G:GG	acceptor_gain	1.0000
19:40205120:GA:G	acceptor_gain	1.0000
19:40205120:GAA:G	acceptor_gain	1.0000
19:40205120:GAAT:G	acceptor_gain	1.0000

AlphaMissense

6122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40192356:T:C	F109L	1.000
19:40192358:T:A	F109L	1.000
19:40192358:T:G	F109L	1.000
19:40192402:T:A	V124D	1.000
19:40192404:A:C	K125Q	1.000
19:40192404:A:G	K125E	1.000
19:40192406:G:C	K125N	1.000
19:40192406:G:T	K125N	1.000
19:40192693:G:C	R221P	1.000
19:40192696:A:C	D222A	1.000
19:40192696:A:T	D222V	1.000
19:40192701:A:G	K224E	1.000
19:40192703:G:C	K224N	1.000
19:40192703:G:T	K224N	1.000
19:40198434:G:C	D248H	1.000
19:40198435:A:C	D248A	1.000
19:40198435:A:G	D248G	1.000
19:40198435:A:T	D248V	1.000
19:40198436:C:A	D248E	1.000
19:40198436:C:G	D248E	1.000
19:40198485:G:A	G265R	1.000
19:40198485:G:C	G265R	1.000
19:40198485:G:T	G265W	1.000
19:40198486:G:A	G265E	1.000
19:40198497:T:A	W269R	1.000
19:40198497:T:C	W269R	1.000
19:40198499:G:C	W269C	1.000
19:40198499:G:T	W269C	1.000
19:40198501:T:C	M270T	1.000
19:40198516:T:A	I275N	1.000

dbSNP variants (sampled 300 via entrez): RS1000070474 (19:40193149 G>A), RS1000142053 (19:40190820 G>A,C,T), RS1000168896 (19:40208319 C>A), RS1000511419 (19:40214258 C>T), RS1000708018 (19:40208565 T>A), RS1000734421 (19:40208326 C>G), RS1000744783 (19:40214588 G>A), RS1000805391 (19:40195595 G>T), RS1000989812 (19:40212523 A>G), RS1001353460 (19:40205177 C>CT), RS1001396478 (19:40207174 A>G), RS1001488773 (19:40200383 C>T), RS1001498719 (19:40200643 G>C), RS1001696451 (19:40194537 G>A), RS1001785045 (19:40201986 C>T)

Disease associations

OMIM: gene MIM:600137 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003818_30	Resting heart rate	1.000000e-11
GCST008362_31	Birth weight	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2873 (SINGLE PROTEIN), CHEMBL6066128 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 85,918 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL290352	CEP-1347	3	359
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MLK subfamily

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

Ligand	Action	Affinity	Parameter
CEP-1347	Inhibition	8.7	pIC50
URMC-099	Inhibition	7.38	pIC50

Binding affinities (BindingDB)

13 measured of 13 human assays (13 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.1^{15,18}.0^{2,6}.0^{7,27}.0^{8,13}.0^{19,26}.0^{20,25}]octacosa-1(26),2(6),7(27),8(13),9,11,20(25),21,23-nonaene-16-carboxylate	IC50	260 nM
3,13-diazahexacyclo[14.8.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tetracosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaene-12,14-dione	IC50	339 nM
3,13-diazahexacyclo[14.7.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tricosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-14-one	IC50	364 nM
3-(2-hydroxyethyl)-20-(propan-2-yloxy)-3,13-diazahexacyclo[14.8.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tetracosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-14-one	IC50	1060 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
3-(2-hydroxyethyl)-20-methoxy-3,13-diazahexacyclo[14.8.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tetracosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-14-one	IC50	1270 nM
3-thia-13,23-diazahexacyclo[14.7.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tricosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-12-one	IC50	2090 nM
3,13-diazahexacyclo[14.7.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tricosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-12-one	IC50	2660 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
3,13-diazahexacyclo[14.8.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tetracosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-12-one	IC50	3450 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

66 potent at pChembl≥5 of 67 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.10	Ki	0.7943	nM	CHEMBL1993661
8.70	IC50	2	nM	CEP-1347
8.57	IC50	2.69	nM	STAUROSPORINE
8.55	IC50	2.84	nM	STAUROSPORINE
8.53	IC50	2.93	nM	STAUROSPORINE
8.50	Ki	3.162	nM	CHEMBL1980995
8.42	Kd	3.8	nM	R-406
8.40	Ki	3.981	nM	R-406
7.82	Kd	15	nM	LESTAURTINIB
7.80	IC50	16	nM	CHEMBL288817
7.70	IC50	20	nM	CHEMBL277817
7.55	IC50	28	nM	CHEMBL288229
7.38	IC50	42	nM	CHEMBL2436978
7.35	IC50	45	nM	CHEMBL416056
7.34	IC50	46	nM	CHEMBL4218417
7.30	IC50	50	nM	CHEMBL4281823
7.29	IC50	51	nM	CEP-1347
7.28	Kd	52	nM	STAUROSPORINE
7.10	Ki	79.43	nM	CHEMBL1991674
7.05	IC50	89	nM	CHEMBL288816
7.00	Ki	100	nM	CHEMBL1972346
6.90	Ki	125.9	nM	CHEMBL1974328
6.90	Ki	125.9	nM	CHEMBL592030
6.85	IC50	140	nM	CHEMBL36891
6.70	Ki	199.5	nM	PF-00562271
6.50	Ki	316.2	nM	CHEMBL458997
6.47	IC50	339	nM	CHEMBL386636
6.44	IC50	364	nM	CHEMBL357490
6.40	Ki	398.1	nM	TOZASERTIB
6.34	IC50	452	nM	CHEMBL2171124
6.28	Kd	530	nM	FORETINIB
6.24	IC50	580	nM	STAUROSPORINE
6.20	IC50	627	nM	CHEMBL29709
6.20	Ki	631	nM	CHEMBL1998953
6.12	IC50	767	nM	CHEMBL3393333
6.10	Kd	790	nM	MIDOSTAURIN
5.96	Kd	1100	nM	TAE-684
5.82	Kd	1500	nM	KW-2449
5.80	IC50	1582	nM	CHEMBL460989
5.80	Ki	1585	nM	CHEMBL1982753
5.80	Ki	1585	nM	DOVITINIB
5.75	Kd	1800	nM	TOZASERTIB
5.73	IC50	1855	nM	CHEMBL460990
5.68	IC50	2088	nM	CHEMBL221536
5.68	Kd	2100	nM	PAZOPANIB
5.64	Kd	2300	nM	NINTEDANIB
5.60	Ki	2512	nM	DASATINIB
5.57	IC50	2664	nM	CHEMBL148471
5.50	Ki	3162	nM	CHEMBL1990496
5.46	IC50	3447	nM	CHEMBL374581

PubChem BioAssay actives

59 with measured affinity, of 330 total; 39 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
methyl (15S,16R,18R)-10,23-bis(ethylsulfanylmethyl)-16-hydroxy-15-methyl-3-oxo-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(13),9,11,20(25),21,23,26-nonaene-16-carboxylate	775351: Inhibition of MLK2 (unknown origin) after 20 mins in presence of [33P]-ATP	ic50	0.0020	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	1531778: Inhibition of human MLK2 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0027	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624867: Binding constant for MLK2 kinase domain	kd	0.0038	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507627: Binding affinity to MLK2	kd	0.0150	uM
methyl (15S,16R,18R)-16-hydroxy-10,23-bis(methoxymethyl)-15-methyl-3-oxo-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(13),9,11,20(25),21,23,26-nonaene-16-carboxylate	125160: Inhibition of Mixed lineage kinase 2(MLK2)	ic50	0.0160	uM
methyl (15S,16R,18R)-10,23-bis(ethoxymethyl)-16-hydroxy-15-methyl-3-oxo-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(13),9,11,20(25),21,23,26-nonaene-16-carboxylate	125160: Inhibition of Mixed lineage kinase 2(MLK2)	ic50	0.0200	uM
methyl (15S,16R,18R)-10-(ethylsulfanylmethyl)-16-hydroxy-15-methyl-3-oxo-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(13),9,11,20,22,24,26-nonaene-16-carboxylate	125160: Inhibition of Mixed lineage kinase 2(MLK2)	ic50	0.0280	uM
3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine	775427: Inhibition of MLK2 (unknown origin)	ic50	0.0420	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-nonaene-16-carboxylate	1797180: Mixed-Lineage Kinase Assays from Article 10.1021/jm051074u: “Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.”	ic50	0.0450	uM
methyl (15R,16S,18S)-16-hydroxy-15-methyl-3-oxo-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-nonaene-16-carboxylate	277638: Inhibition of GST-MLK2	ic50	0.0450	uM
3-(2-hydroxyethyl)-7-(propan-2-yloxymethyl)-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaen-12-one	1384626: Inhibition of recombinant GST-tagged full length human MLK2 KD/LZ expressed in baculovirus using myelin basic protein as substrate preincubated for 15 mins measured after 30 mins in presence of [gamma-32P]ATP by scintillation counting	ic50	0.0460	uM
1-[5-(4-amino-7-ethylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethoxy)phenyl]ethanone	1415194: Inhibition of recombinant human MLK2 (1 to 449 residues) using myelin basic protein as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis	ic50	0.0500	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-10,23-bis(propan-2-ylsulfanylmethyl)-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(13),9,11,20(25),21,23,26-nonaene-16-carboxylate	125160: Inhibition of Mixed lineage kinase 2(MLK2)	ic50	0.0890	uM
methyl (15S,16R,18R)-23-(ethylsulfanylmethyl)-16-hydroxy-15-methyl-3-oxo-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(25),21,23,26-nonaene-16-carboxylate	125160: Inhibition of Mixed lineage kinase 2(MLK2)	ic50	0.1400	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaene-12,14-dione	1797180: Mixed-Lineage Kinase Assays from Article 10.1021/jm051074u: “Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.”	ic50	0.3390	uM
3,13-diazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaen-14-one	1797180: Mixed-Lineage Kinase Assays from Article 10.1021/jm051074u: “Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.”	ic50	0.3640	uM
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone	702101: Inhibition of MLK2	ic50	0.4520	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624867: Binding constant for MLK2 kinase domain	kd	0.5300	uM
methyl (15S,16R,18R)-10,23-bis(butylsulfanylmethyl)-16-hydroxy-15-methyl-3-oxo-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(13),9,11,20(25),21,23,26-nonaene-16-carboxylate	125160: Inhibition of Mixed lineage kinase 2(MLK2)	ic50	0.6270	uM
2-[[6-(3,3-difluoropyrrolidin-1-yl)-4-[1-(oxetan-3-yl)piperidin-4-yl]-2-pyridinyl]amino]pyridine-4-carbonitrile	1189388: Inhibition of MLK2 (unknown origin)	ic50	0.7670	uM
Midostaurin	435432: Binding constant for MLK2 kinase domain	kd	0.7900	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624867: Binding constant for MLK2 kinase domain	kd	1.1000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624867: Binding constant for MLK2 kinase domain	kd	1.5000	uM
3-(2-hydroxyethyl)-20-methoxy-3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17(22),18,20-nonaen-14-one	1798485: Mixed-Lineage Kinase Assay from Article 10.1021/jm8005838: “Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models.”	ic50	1.5820	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435432: Binding constant for MLK2 kinase domain	kd	1.8000	uM
3-(2-hydroxyethyl)-20-propan-2-yloxy-3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17(22),18,20-nonaen-14-one	1798485: Mixed-Lineage Kinase Assay from Article 10.1021/jm8005838: “Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models.”	ic50	1.8550	uM
3-thia-13,23-diazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-12-one	1797180: Mixed-Lineage Kinase Assays from Article 10.1021/jm051074u: “Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.”	ic50	2.0880	uM
Pazopanib	435432: Binding constant for MLK2 kinase domain	kd	2.1000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624867: Binding constant for MLK2 kinase domain	kd	2.3000	uM
3,13-diazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaen-12-one	1797180: Mixed-Lineage Kinase Assays from Article 10.1021/jm051074u: “Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.”	ic50	2.6640	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaen-12-one	1797180: Mixed-Lineage Kinase Assays from Article 10.1021/jm051074u: “Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.”	ic50	3.4470	uM
5,5-dimethyl-8-[[4-(2,2,2-trifluoroethylamino)furo[3,2-d]pyrimidin-2-yl]amino]-1H-4,1-benzoxazepin-2-one	1440135: Inhibition of MAP3K10 (unknown origin) after 60 mins by TR-FRET assay	ic50	4.5500	uM
Neratinib	624867: Binding constant for MLK2 kinase domain	kd	4.6000	uM
5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine	1491962: Inhibition of recombinant human full length GST-tagged MLK2 expressed in baculovirus expression system by FRET assay	ic50	5.1500	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435432: Binding constant for MLK2 kinase domain	kd	5.2000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624867: Binding constant for MLK2 kinase domain	kd	5.3000	uM
Fedratinib	624867: Binding constant for MLK2 kinase domain	kd	6.9000	uM
5-[5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]-1-propan-2-ylpyrazol-3-yl]-3-(trifluoromethoxy)pyridin-2-amine	1491962: Inhibition of recombinant human full length GST-tagged MLK2 expressed in baculovirus expression system by FRET assay	ic50	7.8800	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-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]-N-methylbenzamide	507627: Binding affinity to MLK2	kd	8.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Particulate Matter	increases expression, increases abundance	2
aristolochic acid I	increases expression	1
arsenite	increases methylation	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Asbestos, Crocidolite	affects expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

174 unique, capped per target: 173 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000437	Binding	Inhibition of human MLK2 expressed in baculovirus insect cell system	Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. — J Med Chem
CHEMBL1964110	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP3K10	PubChem BioAssay data set

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3AK	Abcam HEK293T MAP3K10 KO	Transformed cell line	Female
CVCL_SW55	HAP1 MAP3K10 (-) 1	Cancer cell line	Male
CVCL_SW56	HAP1 MAP3K10 (-) 2	Cancer cell line	Male
CVCL_SW57	HAP1 MAP3K10 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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