MAP4K3

Summary

MAP4K3 (mitogen-activated protein kinase kinase kinase kinase 3, HGNC:6865) is a protein-coding gene on chromosome 2p22.1, encoding Mitogen-activated protein kinase kinase kinase kinase 3 (Q8IVH8). Serine/threonine kinase that plays a role in the response to environmental stress.

This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates key effectors in cell signalling, among them c-Jun. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 8491 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 142 total
• Druggable target: yes — 42 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6865
Approved symbol	MAP4K3
Name	mitogen-activated protein kinase kinase kinase kinase 3
Location	2p22.1
Locus type	gene with protein product
Status	Approved
Aliases	GLK, MAPKKKK3
Ensembl gene	ENSG00000011566
Ensembl biotype	protein_coding
OMIM	604921
Entrez	8491

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 15 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000263881, ENST00000341681, ENST00000414968, ENST00000429397, ENST00000437545, ENST00000437968, ENST00000465701, ENST00000474502, ENST00000475457, ENST00000479708, ENST00000484274, ENST00000495648, ENST00000497566, ENST00000934462, ENST00000934463, ENST00000934464, ENST00000934465, ENST00000958528, ENST00000958529, ENST00000958530, ENST00000958531, ENST00000958532, ENST00000958533, ENST00000958534

RefSeq mRNA: 3 — MANE Select: NM_003618 NM_001270425, NM_001410753, NM_003618

CCDS: CCDS1803, CCDS58707, CCDS92741

Canonical transcript exons

ENST00000263881 — 34 exons

Exon	Start	End
ENSE00000748172	39251830	39251885
ENSE00000748773	39267189	39267247
ENSE00000748865	39272283	39272400
ENSE00000749179	39278407	39278486
ENSE00000749566	39282513	39282554
ENSE00000749668	39286852	39286964
ENSE00000749902	39333532	39333574
ENSE00000749914	39336920	39336967
ENSE00000809675	39258348	39258440
ENSE00000809676	39258519	39258587
ENSE00000809677	39260606	39260777
ENSE00000809681	39272482	39272542
ENSE00000809690	39337526	39337581
ENSE00001922471	39436892	39437285
ENSE00001944928	39249266	39250705
ENSE00002437185	39254450	39254520
ENSE00002504102	39280272	39280356
ENSE00002524290	39331917	39331989
ENSE00003459513	39292773	39292826
ENSE00003461419	39293230	39293268
ENSE00003489958	39325518	39325628
ENSE00003502092	39356249	39356339
ENSE00003524087	39265203	39265306
ENSE00003532049	39299743	39299801
ENSE00003580619	39309461	39309519
ENSE00003584393	39325730	39325811
ENSE00003598519	39290292	39290334
ENSE00003613861	39343388	39343452
ENSE00003638861	39288121	39288280
ENSE00003642736	39325899	39325961
ENSE00003645113	39307943	39308005
ENSE00003657312	39315310	39315388
ENSE00003687598	39326146	39326277
ENSE00003703280	39378066	39378123

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1658 / max 490.4365, expressed in 1803 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27926	15.7463	1786
27924	7.5167	1660
27925	0.4799	260
27923	0.4228	252

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.39	gold quality
adrenal tissue	UBERON:0018303	96.05	gold quality
oocyte	CL:0000023	95.84	gold quality
calcaneal tendon	UBERON:0003701	95.31	gold quality
sural nerve	UBERON:0015488	93.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.85	gold quality
tibia	UBERON:0000979	92.41	gold quality
colonic epithelium	UBERON:0000397	92.34	gold quality
gastrocnemius	UBERON:0001388	92.01	gold quality
biceps brachii	UBERON:0001507	92.00	gold quality
endometrium	UBERON:0001295	91.75	gold quality
muscle of leg	UBERON:0001383	91.68	gold quality
jejunal mucosa	UBERON:0000399	91.61	gold quality
jejunum	UBERON:0002115	91.61	gold quality
right ovary	UBERON:0002118	91.23	gold quality
palpebral conjunctiva	UBERON:0001812	90.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.78	gold quality
eye	UBERON:0000970	90.69	gold quality
left ovary	UBERON:0002119	90.61	gold quality
germinal epithelium of ovary	UBERON:0001304	90.58	gold quality
cortical plate	UBERON:0005343	90.56	gold quality
renal medulla	UBERON:0000362	90.47	gold quality
skeletal muscle organ	UBERON:0014892	90.45	gold quality
muscle organ	UBERON:0001630	90.43	gold quality
stomach	UBERON:0000945	90.24	gold quality
ovary	UBERON:0000992	90.23	gold quality
cerebellar hemisphere	UBERON:0002245	90.18	gold quality
cerebellar cortex	UBERON:0002129	90.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	32.71
E-ANND-3	yes	5.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

177 targeting MAP4K3, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7A-5P	99.98	72.29	1790

Literature-anchored findings (GeneRIF, showing 16)

• MAP4K3 orchestrates activation of BAX via the concerted posttranscriptional modulation of PUMA, BAD, and BIM. (PMID:19587239)
• Amino acid sufficiency phosphorylates MAP4K3/Ser170, activating mTORC1, but amino acid restriction causes MAP4K3 to interact with PP2A(T61 epsilon), promoting dephosphorylation of Ser170, MAP4K3 inhibition, and, inhibition of mTORC1 signaling. (PMID:20227368)
• enhanced expression in systemic lupus erythematosus (PMID:21983831)
• Significantly higher median frequencies of circulating GLK-expressing T-cells were observed in patients with adult-onset Still’s disease (31.85%) than in healthy volunteers (8.93%, P <0.001). (PMID:22867055)
• MAP4K3 expression is required for leucine-induced mTORC1 activation in human primary fibroblasts. (PMID:22898570)
• ITGB3 and MAP4K3 are directly repressed by let-7c, altering the metastatic potential of lung cancer cells. (PMID:23981581)
• Data indicate that GLK/MAP4K3 is a prognostic biomarker for non-small cell lung cancer (NSCLC) recurrence. (PMID:27203390)
• hepatocellular carcinoma recurrence may involve germinal center kinase-like kinase (PMID:27343552)
• This report details the first structure of GLK; comparison of its activation loop sequence and P-loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors. (PMID:27727493)
• Authors report that miR-199a-5p and let-7c cooperatively and efficiently inhibit HCC cell migration and invasion by targeting the metastasis promoter MAP4K3 and MAP4K3-mediated drug sensitization. (PMID:28099144)
• MAP4K3 is identified as an amino acid-dependent regulator of autophagy through its phosphorylation of transcription factor EB (TFEB), a transcriptional activator of autophagy. (PMID:29507340)
• MiR-206 contributed to euthyrox resistance in PTC cells through blockage p38 and JNK signaling pathway by targeting MAP4K3. (PMID:30904818)
• The GLK-induced AhR-ROR-gammat (and AhR-phosphorylated ROR-gammat) complex is a therapeutic target for the GLK(high)IL-17A(high) subpopulation of human patients with SLE. (PMID:31318609)
• These findings show the critical role of the GLK-IQGAP cascade in cell migration and tumor metastasis (PMID:31431460)
• MiR-338-3p inhibits growth of glioblastoma through targeting MAP4K3. (PMID:31578840)
• Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus. (PMID:34610951)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	map4k3b	ENSDARG00000071357
danio_rerio	map4k3a	ENSDARG00000087742
mus_musculus	Map4k3	ENSMUSG00000024242
rattus_norvegicus	Map4k3	ENSRNOG00000007172
caenorhabditis_elegans		WBGENE00022603

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), 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

Mitogen-activated protein kinase kinase kinase kinase 3 — Q8IVH8 (reviewed: Q8IVH8)

Alternative names: Germinal center kinase-related protein kinase, MAPK/ERK kinase kinase kinase 3

All UniProt accessions (6): Q8IVH8, F5H5A3, F8WAZ1, F8WBC3, H7C1A4, V9GY95

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase that plays a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway.

Subunit / interactions. Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation.

Tissue specificity. Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IVH8-1	1	yes
Q8IVH8-2	2
Q8IVH8-3	3

RefSeq proteins (3): NP_001257354, NP_001397682, NP_003609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001180	CNH_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR021160	MAPKKKK	Family
IPR050629	STE20/SPS1-PAK	Family

Pfam: PF00069, PF00780

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 (45 total): helix 14, strand 7, turn 4, modified residue 3, sequence variant 3, binding site 3, domain 2, splice variant 2, compositionally biased region 2, chain 1, mutagenesis site 1, sequence conflict 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5J5T	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVH8-F1	71.96	0.43

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): 136 (proton acceptor)

Ligand- & substrate-binding residues (3): 22–30; 45; 48

Post-translational modifications (3): 1, 329, 398

Mutagenesis-validated functional residues (1):

Position	Phenotype
45	loss of kinase activity and ability to activate jnk family.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 290 (showing top): ACTACCT_MIR196A_MIR196B, TGCGCANK_UNKNOWN, GOBP_RESPONSE_TO_PEPTIDE, KEGG_MAPK_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TATTATA_MIR374, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, CATTTCA_MIR203, ONKEN_UVEAL_MELANOMA_UP, PID_TNF_PATHWAY, GOBP_JNK_CASCADE, KMCATNNWGGA_UNKNOWN, ACATTCC_MIR1_MIR206, GOBP_RESPONSE_TO_UV

GO Biological Process (9): protein phosphorylation (GO:0006468), JNK cascade (GO:0007254), response to UV (GO:0009411), response to tumor necrosis factor (GO:0034612), intracellular signal transduction (GO:0035556), MAPK cascade (GO:0000165), stress-activated protein kinase signaling cascade (GO:0031098), cellular senescence (GO:0090398), regulation of intracellular signal transduction (GO:1902531)

GO Molecular Function (11): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), MAP kinase kinase kinase kinase activity (GO:0008349), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), MAP kinase kinase activity (GO:0004708), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), protein kinase binding (GO:0019901)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
MAPK cascade	3
intracellular anatomical structure	2
cellular response to stress	2
intracellular signal transduction	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
response to light stimulus	1
response to cytokine	1
signal transduction	1
intracellular signaling cassette	1
cellular process	1
regulation of signal transduction	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein serine/threonine kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
protein serine/threonine/tyrosine kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
kinase binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP4K3	DBNL	P84070	861
MAP4K3	DBN1	Q16643	818
MAP4K3	SH3GL1	Q99961	724
MAP4K3	RRAGC	Q9HB90	666
MAP4K3	IPMK	Q8NFU5	566
MAP4K3	EFCAB11	Q9BUY7	511
MAP4K3	MRPL11	Q9Y3B7	481
MAP4K3	PIK3C3	Q8NEB9	475
MAP4K3	SOS1	Q07889	461
MAP4K3	MCTP1	Q6DN14	456
MAP4K3	IQCK	Q8N0W5	456
MAP4K3	LIN28B	Q6ZN17	452
MAP4K3	RPL36	Q9Y3U8	450
MAP4K3	RHEB	Q15382	449
MAP4K3	SNRPB2	P08579	433

IntAct

35 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
GRB2	MAP4K3	psi-mi:“MI:0915”(physical association)	0.680
MAP4K3	PRKCQ	psi-mi:“MI:0915”(physical association)	0.640
MAP4K3	PRKCQ	psi-mi:“MI:0914”(association)	0.640
PRKCQ	MAP4K3	psi-mi:“MI:0407”(direct interaction)	0.640
MAP4K3	PRKCQ	psi-mi:“MI:0407”(direct interaction)	0.640
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
MAP4K3	Prkcq	psi-mi:“MI:0914”(association)	0.590
MAP4K3	LCP2	psi-mi:“MI:0407”(direct interaction)	0.590
LCP2	MAP4K3	psi-mi:“MI:0407”(direct interaction)	0.590
MAP4K3	Prkcq	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
Prkcq	MAP4K3	psi-mi:“MI:0915”(physical association)	0.590
MAP4K3	Prkcq	psi-mi:“MI:0915”(physical association)	0.590
MAP4K3	LCP2	psi-mi:“MI:0915”(physical association)	0.590
MAP4K3	MAP4K5	psi-mi:“MI:0915”(physical association)	0.560
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
MAP4K3	PCBP1	psi-mi:“MI:0915”(physical association)	0.400
MAP4K3	NCK1	psi-mi:“MI:0915”(physical association)	0.400
FCRL3	MAP4K3	psi-mi:“MI:0915”(physical association)	0.400
MAP4K3	ZNF423	psi-mi:“MI:0914”(association)	0.350
LOXL2	MAP4K3	psi-mi:“MI:0914”(association)	0.350
LCP2	PRKCQ	psi-mi:“MI:0914”(association)	0.350
	NFIB	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
MAP4K3	PTEN	psi-mi:“MI:2364”(proximity)	0.270
GRB2	MAP4K3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (99): PCBP1 (Affinity Capture-MS), MAP4K3 (Affinity Capture-MS), MAP4K3 (Affinity Capture-MS), MAP4K3 (Affinity Capture-MS), MAP4K3 (Affinity Capture-MS), MAP4K5 (Affinity Capture-MS), MAP4K3 (Affinity Capture-MS), MAP4K3 (Proximity Label-MS), MAP4K3 (Proximity Label-MS), MAP4K3 (Proximity Label-MS), MAP4K3 (Proximity Label-MS), MAP4K3 (Proximity Label-MS), MAP4K3 (Proximity Label-MS), MAP4K3 (Reconstituted Complex), MAP4K3 (Reconstituted Complex)

ESM2 similar proteins: A0A0G2K2P5, A0JNJ1, B1WAP7, G9CGD6, O14640, O75122, O88382, O95049, O97758, P34908, P39447, P51141, P54792, P70175, Q05AS8, Q07157, Q16825, Q5F488, Q5IS48, Q5SGD7, Q5TCQ9, Q5XI81, Q61062, Q62136, Q62728, Q62936, Q6DKE2, Q6P9H4, Q6ZM86, Q812E4, Q86UL8, Q8BMA3, Q8IVH8, Q8JHI3, Q8TDW5, Q920B0, Q924I2, Q925T6, Q92997, Q95168

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0LT89, B0XXN8, B5VNQ3, C4YRB7, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, H2L099, O00506, O14047, O14305, O22040, O22042, O24527, O54748, O61122, O61125, O81472, O95382, P0CY23, P0CY24, P23561, P27636, P28829

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
MAP4K3	up-regulates	MAP4K3	phosphorylation
MAP4K3	up-regulates	PRKCQ	phosphorylation
MAP4K3	“down-regulates activity”	TFEB	phosphorylation
MKRN4P	“down-regulates quantity”	MAP4K3	ubiquitination
MAP4K3	up-regulates	MAP3K1	phosphorylation
MAP4K3	“up-regulates activity”	IQGAP1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5299 predictions. Top by Δscore:

Variant	Effect	Δscore
2:39258343:CTTA:C	donor_loss	1.0000
2:39258344:TTA:T	donor_loss	1.0000
2:39258345:TAC:T	donor_loss	1.0000
2:39258346:A:AC	donor_gain	1.0000
2:39258347:C:CA	donor_loss	1.0000
2:39258347:C:CC	donor_gain	1.0000
2:39258347:CCTA:C	donor_gain	1.0000
2:39258437:CAAC:C	acceptor_gain	1.0000
2:39258440:CCTA:C	acceptor_loss	1.0000
2:39258441:C:CC	acceptor_gain	1.0000
2:39258441:CTAGA:C	acceptor_loss	1.0000
2:39258517:A:AC	donor_gain	1.0000
2:39258517:ACAGT:A	donor_gain	1.0000
2:39258518:C:CC	donor_gain	1.0000
2:39258518:CAGT:C	donor_gain	1.0000
2:39258518:CAGTC:C	donor_gain	1.0000
2:39272277:CCTTA:C	donor_loss	1.0000
2:39272278:CTTA:C	donor_loss	1.0000
2:39272280:TA:T	donor_loss	1.0000
2:39272281:ACCT:A	donor_loss	1.0000
2:39272282:C:CA	donor_loss	1.0000
2:39278402:CATA:C	donor_loss	1.0000
2:39278403:ATAC:A	donor_loss	1.0000
2:39278404:TA:T	donor_loss	1.0000
2:39278406:C:CA	donor_loss	1.0000
2:39278482:CTGAT:C	acceptor_gain	1.0000
2:39278487:C:CC	acceptor_gain	1.0000
2:39286850:A:AC	donor_gain	1.0000
2:39286851:C:CC	donor_gain	1.0000
2:39288197:C:CA	donor_gain	1.0000

AlphaMissense

5906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:39250643:A:G	L887P	1.000
2:39250643:A:T	L887Q	1.000
2:39250694:A:G	L870S	1.000
2:39251877:T:A	Q850H	1.000
2:39251877:T:G	Q850H	1.000
2:39254472:C:T	G840D	1.000
2:39254473:C:G	G840R	1.000
2:39254475:T:G	Q839P	1.000
2:39254481:C:A	G837V	1.000
2:39254481:C:T	G837E	1.000
2:39254496:G:T	A832D	1.000
2:39254499:A:G	L831P	1.000
2:39254499:A:T	L831Q	1.000
2:39254514:A:G	L826P	1.000
2:39258377:A:G	L814P	1.000
2:39258413:C:A	G802V	1.000
2:39258413:C:T	G802E	1.000
2:39258414:C:G	G802R	1.000
2:39258414:C:T	G802R	1.000
2:39258533:A:G	L788P	1.000
2:39265238:A:G	W701R	1.000
2:39265238:A:T	W701R	1.000
2:39265276:A:G	L688P	1.000
2:39272525:A:C	C604W	1.000
2:39278438:A:G	L588P	1.000
2:39278444:A:G	L586P	1.000
2:39278451:A:C	Y584D	1.000
2:39278456:C:A	G582V	1.000
2:39278456:C:T	G582E	1.000
2:39278457:C:A	G582W	1.000

dbSNP variants (sampled 300 via entrez): RS1000000766 (2:39432850 A>G), RS1000006435 (2:39304621 G>A), RS1000025140 (2:39320533 T>A), RS1000037020 (2:39391577 C>T), RS1000041865 (2:39409608 T>G), RS1000065615 (2:39356606 G>A,T), RS1000081355 (2:39346391 G>C), RS1000081924 (2:39299699 A>G,T), RS1000083179 (2:39315135 C>T), RS1000108454 (2:39369252 G>A,C), RS1000125343 (2:39335380 G>A,C), RS1000141056 (2:39391919 A>C,G), RS1000142629 (2:39319182 C>T), RS1000143621 (2:39384743 T>C), RS1000158455 (2:39417018 G>C,T)

Disease associations

OMIM: gene MIM:604921 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): ependymoma (MONDO:0016698)

Orphanet (1): Ependymoma (Orphanet:251636)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009377_1	Bone mineral density	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007620	volumetric bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5432 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

42 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 261,255 (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
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL1091644	LINSITINIB	3	1,446
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230609	FORETINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL253969	OSI-632	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — KHS subfamily

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

Ligand	Action	Affinity	Parameter
RIPK3 inhibitor 18	Inhibition	7.92	pIC50
compound 8h [PMID: 22765894]	Inhibition	7.6	pIC50
compound 5i [PMID: 36542759]	Inhibition	7.09	pIC50

Binding affinities (BindingDB)

96 measured of 96 human assays (96 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20250361241, Compound 2B	IC50	1.02 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 47	IC50	1.51 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
Staurosporine	KD	1.7 nM
US20250361241, Compound 29	IC50	1.98 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 48	IC50	2.06 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 60	IC50	2.14 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 37	IC50	2.25 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 67	IC50	2.49 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 86	IC50	2.61 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 110	IC50	2.67 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 36	IC50	2.73 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 39	IC50	2.78 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 75	IC50	2.78 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 38	IC50	2.92 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 70	IC50	2.99 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 158A	IC50	3 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 74	IC50	3.02 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 44	IC50	3.05 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 122	IC50	3.21 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 71	IC50	3.27 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 108	IC50	3.29 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 121	IC50	3.35 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 50	IC50	3.39 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 106	IC50	3.46 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 73	IC50	3.48 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 104	IC50	3.49 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 76	IC50	3.55 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 107	IC50	3.55 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 161	IC50	3.57 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 41	IC50	3.76 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 3	IC50	4.16 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 43	IC50	4.22 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 146	IC50	4.33 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 49	IC50	4.44 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 32	IC50	4.52 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 42	IC50	4.62 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 103	IC50	4.67 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 33	IC50	4.76 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 117	IC50	5.04 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 87	IC50	5.12 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 85	IC50	5.19 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 101	IC50	5.22 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 127	IC50	5.23 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 58	IC50	5.25 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 168	IC50	5.27 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 88	IC50	5.29 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 90	IC50	5.58 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 157	IC50	5.9 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 109	IC50	5.97 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF
US20250361241, Compound 59	IC50	6.09 nM	US-20250361241: HPK1 INHIBITOR AND MEDICAL USE THEREOF

ChEMBL bioactivities

250 potent at pChembl≥5 of 256 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.08	IC50	0.0825	nM	STAUROSPORINE
10.08	IC50	0.0833	nM	STAUROSPORINE
9.87	IC50	0.135	nM	STAUROSPORINE
9.34	IC50	0.46	nM	CHEMBL4780798
9.31	IC50	0.49	nM	CHEMBL5505932
9.14	IC50	0.72	nM	CHEMBL5999390
9.10	IC50	0.8	nM	CHEMBL5428695
8.82	IC50	1.5	nM	CHEMBL4778959
8.52	IC50	3	nM	CHEMBL4749141
8.52	IC50	3	nM	CHEMBL5396693
8.40	IC50	4	nM	CHEMBL6133969
8.30	IC50	5	nM	CHEMBL4762312
8.29	Kd	5.1	nM	BOSUTINIB
8.15	IC50	7	nM	CHEMBL5397290
8.12	IC50	7.56	nM	CHEMBL5558185
8.11	Kd	7.7	nM	NERATINIB
8.09	Kd	8.2	nM	STAUROSPORINE
7.99	IC50	10.22	nM	CHEMBL5555917
7.97	IC50	10.8	nM	CHEMBL6190046
7.92	IC50	12	nM	CHEMBL4753188
7.83	IC50	14.67	nM	CHEMBL5555788
7.78	IC50	16.7	nM	CHEMBL5407530
7.77	IC50	17	nM	CHEMBL4793665
7.77	IC50	17	nM	CHEMBL6160518
7.75	IC50	18	nM	CHEMBL4782885
7.72	IC50	19	nM	CHEMBL6150979
7.65	IC50	22.32	nM	CHEMBL5555659
7.64	IC50	23	nM	CHEMBL6152052
7.62	IC50	24	nM	CHEMBL4568440
7.60	IC50	25	nM	CHEMBL2086760
7.57	IC50	27.04	nM	CHEMBL6141676
7.56	IC50	27.8	nM	CHEMBL5417139
7.55	IC50	28.44	nM	CHEMBL6102008
7.52	IC50	30.24	nM	CHEMBL5558967
7.51	IC50	31	nM	CHEMBL4790577
7.48	Kd	33	nM	Cerdulatinib Hydrochloride
7.48	IC50	33	nM	CHEMBL4788727
7.46	IC50	35	nM	CHEMBL4785602
7.44	IC50	36	nM	CHEMBL5398202
7.44	IC50	36.67	nM	CHEMBL6101966
7.41	IC50	39	nM	CHEMBL518323
7.39	IC50	41	nM	CHEMBL4789200
7.38	IC50	42.2	nM	CHEMBL4748154
7.37	IC50	43	nM	CHEMBL4750822
7.37	IC50	43	nM	CHEMBL4759406
7.34	IC50	46	nM	CHEMBL4784181
7.31	Kd	49	nM	AZD-4547
7.31	IC50	49	nM	CRIZOTINIB
7.27	IC50	53.6	nM	CHEMBL5403199
7.24	Kd	58	nM	BOSUTINIB

PubChem BioAssay actives

185 with measured affinity, of 607 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(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	1531706: Inhibition of human GLK using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
5-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0005	uM
5-amino-2-[(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)amino]-8-[[2-(trifluoromethyl)phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2062030: Inhibition of GLK (unknown origin) by ADP-Glo assay	ic50	0.0005	uM
N-(3,3-dimethyl-1H-2-benzofuran-5-yl)-7-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)quinazolin-2-amine	1975904: Inhibition of GLK (unknown origin)	ic50	0.0008	uM
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-[3-(1-methylpiperidin-4-yl)-1,2,4-oxadiazol-5-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0015	uM
5-(2-piperidin-4-yl-1,3-thiazol-5-yl)-3-(pyridin-4-ylmethoxy)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0030	uM
N-[4-(1-methylpiperidin-4-yl)phenyl]-7-(1-methylpyrazol-4-yl)quinazolin-2-amine	1975904: Inhibition of GLK (unknown origin)	ic50	0.0030	uM
2-(2,6-dichloro-3-fluorophenyl)-4-(1-piperidin-4-ylpyrazol-4-yl)furo[2,3-c]pyridin-7-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0050	uM
Bosutinib	1679423: Inhibition of GLK (unknown origin)	kd	0.0051	uM
3-[4-[(3aR,7aR)-1,2,3,3a,5,6,7,7a-octahydropyrrolo[3,2-b]pyridin-4-yl]-6-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile	2029416: Inhibition of MAP4K3 (unknown origin) by by FRET based Z’-LYTE assay	ic50	0.0070	uM
3-(3-fluoro-4-methoxyphenyl)-5-[4-(4-methylpiperazin-1-yl)phenyl]-2H-pyrazolo[3,4-b]pyridine	2068001: Inhibition of GLK (unknown origin)	ic50	0.0076	uM
Neratinib	624921: Binding constant for MAP4K3 kinase domain	kd	0.0077	uM
3-(4-methoxyphenyl)-5-[4-(4-methylpiperazin-1-yl)phenyl]-2H-pyrazolo[3,4-b]pyridine	2068001: Inhibition of GLK (unknown origin)	ic50	0.0102	uM
2-(3-fluorophenyl)-5-(1-piperidin-4-ylpyrazol-4-yl)-1,7-naphthyridin-8-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0120	uM
3-(3,4-dimethoxyphenyl)-5-[4-(4-methylpiperazin-1-yl)phenyl]-2H-pyrazolo[3,4-b]pyridine	2068001: Inhibition of GLK (unknown origin)	ic50	0.0147	uM
(9S)-9-(hydroxymethyl)-6-(1-piperidin-4-ylpyrazol-4-yl)-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964748: Inhibition of GLK (unknown origin) using MBP protein as substrate in presence of ATP preincubated for 15 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay	ic50	0.0167	uM
5-[2-(1-ethylpiperidin-4-yl)-1,3-thiazol-5-yl]-3-(pyridin-4-ylmethoxy)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0170	uM
2-(3-fluorophenyl)-4-(1-piperidin-4-ylpyrazol-4-yl)furo[2,3-c]pyridin-7-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0180	uM
3-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[4-(4-methylpiperazin-1-yl)phenyl]-2H-pyrazolo[3,4-b]pyridine	2068001: Inhibition of GLK (unknown origin)	ic50	0.0223	uM
3-[1-(2,6-dichloro-3-fluorophenyl)propoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0240	uM
3-[(4-chlorophenyl)-(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1H-indol-2-one	684381: Inhibition of MAP4K3	ic50	0.0250	uM
(9S)-6-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-9-(hydroxymethyl)-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964748: Inhibition of GLK (unknown origin) using MBP protein as substrate in presence of ATP preincubated for 15 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay	ic50	0.0278	uM
3-(3-chloro-4-methoxyphenyl)-5-[4-(4-methylpiperazin-1-yl)phenyl]-2H-pyrazolo[3,4-b]pyridine	2068001: Inhibition of GLK (unknown origin)	ic50	0.0302	uM
3-N-[(2,6-dichloro-3-fluorophenyl)methyl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridine-2,3-diamine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0310	uM
5-(1-piperidin-4-ylpyrazol-4-yl)-3-(pyridin-4-ylmethoxy)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0330	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1425053: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0330	uM
3-cyclohexyloxy-5-(2-piperidin-4-yl-1,3-thiazol-5-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0350	uM
3-[4-[(3S,4R)-3-amino-4-fluoropiperidin-1-yl]-6-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile	2029416: Inhibition of MAP4K3 (unknown origin) by by FRET based Z’-LYTE assay	ic50	0.0360	uM
3-[(2,6-dichloro-3-fluorophenyl)methoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0390	uM
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0410	uM
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	2023056: Inhibition of N-terminal GST-tagged human recombinant GLK (1 to 380 residues) expressed in baculovirus-infected Sf9 cells using PKA substrate by ADP-Glo kinase assay	ic50	0.0422	uM
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0430	uM
5-[[5-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0430	uM
5-[[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0460	uM
Crizotinib	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0490	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide	1425053: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0490	uM
(9S)-9-(hydroxymethyl)-6-(1-methylpyrazol-4-yl)-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964748: Inhibition of GLK (unknown origin) using MBP protein as substrate in presence of ATP preincubated for 15 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay	ic50	0.0536	uM
5-[[4-[[(1S)-2,2-dideuterio-1-(4-fluorophenyl)-2-hydroxyethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2H-isoindol-1-one	2023056: Inhibition of N-terminal GST-tagged human recombinant GLK (1 to 380 residues) expressed in baculovirus-infected Sf9 cells using PKA substrate by ADP-Glo kinase assay	ic50	0.0607	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	624921: Binding constant for MAP4K3 kinase domain	kd	0.0650	uM
(9S)-6-[1-(2-hydroxyethyl)pyrazol-4-yl]-9-(hydroxymethyl)-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964748: Inhibition of GLK (unknown origin) using MBP protein as substrate in presence of ATP preincubated for 15 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay	ic50	0.0668	uM
5-[[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0680	uM
3-(cyclohexylmethoxy)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0740	uM
3-cyclohexyloxy-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0760	uM
5-(1-piperidin-4-ylpyrazol-4-yl)-3-(pyridazin-4-ylmethoxy)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0770	uM
3-(cyclohexylmethoxy)-5-(2-piperidin-4-yl-1,3-thiazol-5-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0770	uM
ethyl 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxylate	1694482: Inhibition of GLK (unknown origin)	ic50	0.0790	uM
2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-methylpyrimidine-5-carboxamide	1694482: Inhibition of GLK (unknown origin)	ic50	0.0800	uM
(9S)-9-(hydroxymethyl)-6-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964748: Inhibition of GLK (unknown origin) using MBP protein as substrate in presence of ATP preincubated for 15 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay	ic50	0.0810	uM
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(5-methyl-1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	1694482: Inhibition of GLK (unknown origin)	ic50	0.0850	uM
3-(2-phenylethynyl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine	1679862: Inhibition of GLK (unknown origin) by alphascreen assay	ic50	0.0870	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects binding, increases reaction	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
ciglitazone	affects binding, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
asparanin A	decreases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Glyphosate	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1

ChEMBL screening assays

157 unique, capped per target: 157 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017057	Binding	Binding affinity to MAP4K3	Examining 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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WN	Abcam HeLa MAP4K3 KO	Cancer cell line	Female
CVCL_D7UG	Ubigene A-549 MAP4K3 KO	Cancer cell line	Male
CVCL_E0HD	Ubigene HeLa MAP4K3 KO	Cancer cell line	Female
CVCL_SW81	HAP1 MAP4K3 (-) 1	Cancer cell line	Male
CVCL_SW82	HAP1 MAP4K3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	PHASE3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
NCT00003479	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	PHASE2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	PHASE2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	PHASE2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	PHASE2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03727841	PHASE2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04743661	PHASE2	ACTIVE_NOT_RECRUITING	131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07424092	PHASE2	RECRUITING	Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors
NCT00634231	PHASE1	COMPLETED	A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
NCT00994071	PHASE1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT01171469	PHASE1	COMPLETED	Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01498783	PHASE1	COMPLETED	Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma