MAP3K4

Summary

MAP3K4 (mitogen-activated protein kinase kinase kinase 4, HGNC:6856) is a protein-coding gene on chromosome 6q26, encoding Mitogen-activated protein kinase kinase kinase 4 (Q9Y6R4). Component of a protein kinase signal transduction cascade.

The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described.

Source: NCBI Gene 4216 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 240 total
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6856
Approved symbol	MAP3K4
Name	mitogen-activated protein kinase kinase kinase 4
Location	6q26
Locus type	gene with protein product
Status	Approved
Aliases	MTK1, MAPKKK4, KIAA0213
Ensembl gene	ENSG00000085511
Ensembl biotype	protein_coding
OMIM	602425
Entrez	4216

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 7 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000348824, ENST00000366919, ENST00000366920, ENST00000392142, ENST00000446500, ENST00000448119, ENST00000490904, ENST00000536852, ENST00000539610, ENST00000540205, ENST00000541901, ENST00000542851, ENST00000542952, ENST00000543421, ENST00000544041, ENST00000544733, ENST00000875639, ENST00000922279, ENST00000922280, ENST00000922281, ENST00000946145, ENST00000946146, ENST00000946147, ENST00000946148, ENST00000946149

RefSeq mRNA: 5 — MANE Select: NM_005922 NM_001291958, NM_001301072, NM_001363582, NM_005922, NM_006724

CCDS: CCDS34565, CCDS34566, CCDS75544, CCDS87464

Canonical transcript exons

ENST00000392142 — 27 exons

Exon	Start	End
ENSE00001148239	161048616	161049979
ENSE00002301246	160991769	160992083
ENSE00003460941	161089322	161089471
ENSE00003475034	161092010	161092143
ENSE00003494447	161092978	161093056
ENSE00003498080	161086584	161086667
ENSE00003517218	161086379	161086478
ENSE00003517701	161106514	161106705
ENSE00003529849	161091379	161091540
ENSE00003566471	161108743	161108859
ENSE00003578962	161070608	161070850
ENSE00003581289	161034259	161034449
ENSE00003590889	161112668	161112774
ENSE00003612264	161109755	161109914
ENSE00003612400	161080881	161081038
ENSE00003612694	161102699	161102779
ENSE00003613628	161098278	161098427
ENSE00003620487	161097080	161097176
ENSE00003628010	161101892	161101992
ENSE00003637666	161093773	161093851
ENSE00003646780	161087688	161087954
ENSE00003648222	161115123	161115302
ENSE00003648610	161107899	161107969
ENSE00003659237	161111836	161111958
ENSE00003665222	161073466	161073612
ENSE00003688242	161084501	161084617
ENSE00003848857	161116850	161117380

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 95.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5904 / max 224.5924, expressed in 1805 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71041	14.5193	1785
71038	1.7743	1000
71045	0.5746	98
71042	0.5706	334
71039	0.4074	206
71053	0.2940	41
71044	0.2850	85
71037	0.2529	133
71040	0.2223	95
71047	0.2048	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.19	gold quality
esophagus squamous epithelium	UBERON:0006920	94.69	gold quality
secondary oocyte	CL:0000655	94.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.46	gold quality
sural nerve	UBERON:0015488	94.45	gold quality
squamous epithelium	UBERON:0006914	94.30	gold quality
calcaneal tendon	UBERON:0003701	94.20	gold quality
gingival epithelium	UBERON:0001949	94.15	gold quality
oral cavity	UBERON:0000167	94.14	gold quality
lower esophagus mucosa	UBERON:0035834	94.10	gold quality
epithelium of esophagus	UBERON:0001976	93.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.42	gold quality
gingiva	UBERON:0001828	93.41	gold quality
pancreatic ductal cell	CL:0002079	93.40	gold quality
right uterine tube	UBERON:0001302	93.37	gold quality
cerebellar hemisphere	UBERON:0002245	93.35	gold quality
tongue squamous epithelium	UBERON:0006919	93.33	gold quality
cerebellar cortex	UBERON:0002129	93.25	gold quality
cervix squamous epithelium	UBERON:0006922	93.25	gold quality
amniotic fluid	UBERON:0000173	93.16	gold quality
ectocervix	UBERON:0012249	93.16	gold quality
bronchial epithelial cell	CL:0002328	92.93	gold quality
uterine cervix	UBERON:0000002	92.84	gold quality
parotid gland	UBERON:0001831	92.84	gold quality
tibial nerve	UBERON:0001323	92.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.62	gold quality
body of uterus	UBERON:0009853	92.62	gold quality
epithelium of nasopharynx	UBERON:0001951	92.59	gold quality
epithelium of bronchus	UBERON:0002031	92.42	gold quality
cerebellum	UBERON:0002037	92.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.45
E-CURD-11	no	153.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, JUN, TAL1

miRNA regulators (miRDB)

94 targeting MAP3K4, 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-3924	100.00	72.09	2394
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690

Literature-anchored findings (GeneRIF, showing 21)

• Axin utilizes distinct regions for competitive MEKK1 and MEKK4 binding and JNK activation. (PMID:12878610)
• MEKK4 is the MAPK kinase kinase for TRAF4 regulation of the JNK pathway (PMID:16157600)
• Taken together, these results indicate a novel role for CIN85 in the regulation of cellular stress response via the MAPK pathways. (PMID:16256071)
• In this review, the role of MKK4 in cancer development appears complex, as some studies support a pro-oncogenic role for MKK4, while others suggest it may have tumor suppressor functions. (PMID:17496914)
• CIN85 binding to a C-terminal motif within hTTP leads to the increased phosphorylation of hTTP, possibly through enhanced association with MEKK4 (PMID:20221403)
• The upstream molecule of the TRAIL-induced MAPK activation is MEKK, as opposed to ASK1, via the mediation of its signal through JNK/p38 in a caspase-8-dependent manner. (PMID:21152872)
• For the first time we report a significant association between nicotine dependence and DRD5, NPY1R MAP3K4 single nucleotide polymorphism. (PMID:22309839)
• we have identified a reduced IL-1A response, related to a low MAP3K4 expression and high expression of its inhibitor GSK3beta, identifying a novel key player in Crohn’s disease. (PMID:22732089)
• MAP3K4 is sufficiently mediate the TGFbeta-induced phosphorylation of p38 MAPK in MEFs and HaCaT cells. (PMID:23760366)
• MTK1 was identified in the HER2/HER3-HRG mediated extracellular acidification and cell migration pathway in breast cancer cells. (PMID:24036211)
• Map3k4 haploinsufficiency is the cause of T-associated sex reversal. (PMID:24452333)
• Mutations in genes such as AKT2, CCNA1, MAP3K4, and TGFBR1, were associated significantly with Epstein-Barr-positive gastric tumors, compared with EBV-negative tumors. (PMID:25173755)
• IL-21 expression is promoted by MEKK4 in malignant T cells and is associated with progression risk in cutaneous T-cell lymphoma (PMID:26802931)
• MAP3K4 was up-regulated and its expression was inversely correlated with collagen expression in the osteoblasts from older donors. (PMID:30217450)
• These mutations increase the binding of the RHOA, MAP3K4 and FRAT1 proteins and generally decrease the binding of RAC1. Thus, pathologies in MAP3K1 disrupt the balance between the pro-kinase activities of the RHOA and MAP3K4 binding partners and the inhibitory activity of RAC1. (PMID:30608580)
• A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. (PMID:31915244)
• Coordinated regulation of Rel expression by MAP3K4, CBP, and HDAC6 controls phenotypic switching. (PMID:32859943)
• Association between MAP3K4 gene polymorphisms and the risk of schizophrenia susceptibility in a Northeast Chinese Han population. (PMID:35445959)
• CircMAP3K4 protects human lens epithelial cells from H2O2-induced dysfunction by targeting miR-193a-3p/PLCD3 axis in age-related cataract. (PMID:36071682)
• Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease. (PMID:36376950)
• CircMAP3K4 Suppresses H2O2-Induced Human Lens Epithelial Cell Injury by miR-630/ERCC6 Axis in Age-Related Cataract. (PMID:38152055)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Map3k4	ENSMUSG00000014426
rattus_norvegicus	Map3k4	ENSRNOG00000017419
drosophila_melanogaster	lic	FBGN0261524
caenorhabditis_elegans		WBGENE00004758
caenorhabditis_elegans		WBGENE00018034
caenorhabditis_elegans		WBGENE00018035

Paralogs (8): MAP2K4 (ENSG00000065559), MAP2K7 (ENSG00000076984), MAP2K2 (ENSG00000126934), NEK1 (ENSG00000137601), MAP2K5 (ENSG00000137764), MAP2K1 (ENSG00000169032), MAP3K2 (ENSG00000169967), MAP3K3 (ENSG00000198909)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase 4 — Q9Y6R4 (reviewed: Q9Y6R4)

Alternative names: MAP three kinase 1, MAPK/ERK kinase kinase 4

All UniProt accessions (7): Q9Y6R4, F5H1X6, F5H2S6, F5H4R1, F5H534, F5H538, J3KNB8

UniProt curated annotations — full annotation on UniProt →

Function. Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.

Subunit / interactions. Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1. Interacts with GADD45 and MAP2K6. Interacts with ZFP36; this interaction enhances the association with SH3KBP1/CIN85. Interacts with SH3KBP1; this interaction enhances the association with ZFP36. Interacts with CDC42.

Subcellular location. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels in other tissues.

Activity regulation. N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1505.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6R4-1	1, A	yes
Q9Y6R4-2	2, B

RefSeq proteins (5): NP_001278887, NP_001288001, NP_001350511, NP_005913, NP_006715 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR045801	MEKK4_N	Domain
IPR050538	MAP_kinase_kinase_kinase	Family

Pfam: PF00069, PF19431

Enzyme classification (BRENDA):

• EC 2.7.12.2 — mitogen-activated protein kinase kinase (BRENDA: 38 organisms, 149 substrates, 134 inhibitors, 6 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0533	1
ERK2	0.0002	1
K52R-[ERK2]	0.0001	1
K53M-[P38ALPHA]	0.0002	1
P38ALPHA	0.0002	1

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 (43 total): modified residue 11, sequence variant 8, compositionally biased region 7, region of interest 5, sequence conflict 5, binding site 2, chain 1, domain 1, active site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6R4-F1	66.66	0.21

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): 1463 (proton acceptor)

Ligand- & substrate-binding residues (2): 1349–1357; 1372

Post-translational modifications (11): 84, 431, 447, 456, 457, 458, 461, 481, 499, 1252, 1274

Mutagenesis-validated functional residues (1):

Position	Phenotype
1372	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_UV_C, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_MALE_SEX_DETERMINATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_SEX_DETERMINATION, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, YY1_Q6, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (12): MAPK cascade (GO:0000165), placenta development (GO:0001890), response to UV-C (GO:0010225), regulation of gene expression (GO:0010468), male germ-line sex determination (GO:0019100), positive regulation of telomere maintenance (GO:0032206), intracellular signal transduction (GO:0035556), p38MAPK cascade (GO:0038066), positive regulation of JUN kinase activity (GO:0043507), chorionic trophoblast cell differentiation (GO:0060718), positive regulation of p38MAPK cascade (GO:1900745), protein phosphorylation (GO:0006468)

GO Molecular Function (10): MAP kinase kinase kinase activity (GO:0004709), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
MAPK cascade	2
protein kinase activity	2
cellular anatomical structure	2
intracellular signaling cassette	1
animal organ development	1
response to UV	1
gene expression	1
regulation of macromolecule biosynthetic process	1
primary sex determination, germ-line	1
germ-line sex determination	1
male sex determination	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
signal transduction	1
JUN kinase activity	1
positive regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
cell differentiation	1
chorion development	1
p38MAPK cascade	1
positive regulation of MAPK cascade	1
regulation of p38MAPK cascade	1
phosphorylation	1
protein modification process	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1

Protein interactions and networks

STRING

1410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP3K4	GADD45B	O75293	989
MAP3K4	GADD45A	P24522	988
MAP3K4	GADD45G	O95257	938
MAP3K4	CDC42	P21181	895
MAP3K4	GPR132	Q9UNW8	761
MAP3K4	GPR68	Q15743	761
MAP3K4	GPR4	P46093	760
MAP3K4	DIXDC1	Q155Q3	697
MAP3K4	FRAT1	Q92837	695
MAP3K4	MAP3K1	Q13233	650
MAP3K4	DDIT3	P35638	559
MAP3K4	MAP2K4	P45985	545
MAP3K4	RHOA	P06749	535
MAP3K4	MAP2K3	P46734	499
MAP3K4	AXIN1	O15169	494

IntAct

75 interactions, top by confidence:

A	B	Type	Score
MAP3K4	GADD45A	psi-mi:“MI:0915”(physical association)	0.680
MAP3K4	GADD45B	psi-mi:“MI:0915”(physical association)	0.680
GADD45G	MAP3K4	psi-mi:“MI:0915”(physical association)	0.630
USP20	HIF1A	psi-mi:“MI:0914”(association)	0.630
SH3KBP1	MAP3K4	psi-mi:“MI:0915”(physical association)	0.590
MAP3K4	SH3KBP1	psi-mi:“MI:0915”(physical association)	0.590
GADD45G	MIDN	psi-mi:“MI:0914”(association)	0.550
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
MAP2K6	MAP3K4	psi-mi:“MI:0915”(physical association)	0.520
GADD45A	MAP2K6	psi-mi:“MI:0915”(physical association)	0.520
MAP2K6	MAP3K4	psi-mi:“MI:2364”(proximity)	0.520
UBC	MAP3K4	psi-mi:“MI:0915”(physical association)	0.520
MAP3K4	UBC	psi-mi:“MI:0915”(physical association)	0.520
MAP3K4	USP20	psi-mi:“MI:0915”(physical association)	0.500
FLNB	RAC1	psi-mi:“MI:0914”(association)	0.500
MAP3K4	FLNB	psi-mi:“MI:0915”(physical association)	0.500
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PTK2B	MAP3K4	psi-mi:“MI:0403”(colocalization)	0.460
PTK2B	MAP3K4	psi-mi:“MI:0915”(physical association)	0.460
MAP3K4	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP3K4	RPS25	psi-mi:“MI:0915”(physical association)	0.400
MAP3K4	BOP1	psi-mi:“MI:0915”(physical association)	0.400
MAP3K4	PTPN6	psi-mi:“MI:0403”(colocalization)	0.400
ANXA2	MAP3K4	psi-mi:“MI:0915”(physical association)	0.400
PTPN6	MAP3K4	psi-mi:“MI:0203”(dephosphorylation reaction)	0.400

BioGRID (120): MAP3K4 (Biochemical Activity), MAP2K6 (Biochemical Activity), MAP3K4 (Biochemical Activity), AXIN1 (Affinity Capture-Western), MAP3K4 (Affinity Capture-Western), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS), MAP3K4 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GUA6, A0JMD2, A2VCZ5, A5WUT8, A6H5Y1, A6NKB5, B8JKP6, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14513, O60284, P0CAX8, Q0P4S0, Q15468, Q1LV19, Q1RMQ5, Q4V7H1, Q5DU28, Q5DW34, Q5REU9, Q5SW75, Q5SWW4, Q5U4U4, Q5ZM13, Q60664, Q60988, Q6P9N1, Q6ZPK7, Q76I76, Q76I79, Q80TA9, Q80TY4, Q8BLN6, Q8BYM7, Q8IWB6, Q8JGS1, Q8K2J4

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0XXN8, B5VNQ3, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, O08648, O14047, O14299, O22040, O22042, O35099, O54748, O61122, O74304, O81472, O95382, P23561, P25390, P28829, P41892, P53349, P53599, Q01389, Q03497

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
AXIN1	up-regulates	MAP3K4	binding
MAP3K4	“up-regulates activity”	MAP3K4	phosphorylation
GSK3B	down-regulates	MAP3K4	binding
MAP3K4	“up-regulates activity”	MAPK14
“UV stress”	up-regulates	MAP3K4
MAP3K4	“up-regulates activity”	MAP2K3	phosphorylation
MAP3K4	“up-regulates activity”	MAP2K6	phosphorylation
MAP3K4	“up-regulates activity”	MAP2K4	phosphorylation
MAP3K7	“up-regulates activity”	MAP3K4

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:

Pathway	Partners	Fold	FDR
Parasite infection	5	29.8×	1e-04
Leishmania phagocytosis	5	29.8×	1e-04
RHO GTPases Activate WASPs and WAVEs	5	27.4×	1e-04
Fcgamma receptor (FCGR) dependent phagocytosis	5	24.0×	2e-04
EPHB-mediated forward signaling	5	22.9×	2e-04
FCGR3A-mediated phagocytosis	6	19.4×	1e-04
Regulation of actin dynamics for phagocytic cup formation	6	19.1×	1e-04
Activation of STAT3 by cadherin engagement	6	16.9×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
cell motility	5	27.1×	4e-04
positive regulation of JNK cascade	7	15.5×	3e-04
axonogenesis	5	10.8×	6e-03
regulation of actin cytoskeleton organization	5	10.6×	6e-03
actin filament organization	6	9.6×	4e-03
endocytosis	6	7.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	187
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

5378 predictions. Top by Δscore:

Variant	Effect	Δscore
6:160992082:AGGT:A	donor_loss	1.0000
6:160992084:GTGA:G	donor_loss	1.0000
6:160992085:T:G	donor_loss	1.0000
6:161034243:ACACT:A	acceptor_gain	1.0000
6:161034258:GGCAA:G	acceptor_gain	1.0000
6:161034445:GAAAG:G	donor_gain	1.0000
6:161034450:G:A	donor_loss	1.0000
6:161034451:T:A	donor_loss	1.0000
6:161048611:A:AG	acceptor_gain	1.0000
6:161048614:A:AG	acceptor_gain	1.0000
6:161048615:G:GG	acceptor_gain	1.0000
6:161048615:GA:G	acceptor_gain	1.0000
6:161048615:GAA:G	acceptor_gain	1.0000
6:161048615:GAAA:G	acceptor_gain	1.0000
6:161048615:GAAAA:G	acceptor_gain	1.0000
6:161070606:A:AG	acceptor_gain	1.0000
6:161070607:G:GG	acceptor_gain	1.0000
6:161070607:GTTTT:G	acceptor_gain	1.0000
6:161070797:T:G	donor_gain	1.0000
6:161070836:T:G	donor_gain	1.0000
6:161070836:T:TG	donor_gain	1.0000
6:161071308:G:A	acceptor_gain	1.0000
6:161073460:TTGCA:T	acceptor_loss	1.0000
6:161073461:TGCAG:T	acceptor_loss	1.0000
6:161073462:GCA:G	acceptor_loss	1.0000
6:161073463:CAGC:C	acceptor_loss	1.0000
6:161073464:A:AG	acceptor_gain	1.0000
6:161073464:A:T	acceptor_loss	1.0000
6:161073464:AGCT:A	acceptor_gain	1.0000
6:161073465:G:A	acceptor_loss	1.0000

AlphaMissense

10614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:161049065:T:A	W265R	1.000
6:161049065:T:C	W265R	1.000
6:161049075:T:C	L268P	1.000
6:161049458:T:A	W396R	1.000
6:161049458:T:C	W396R	1.000
6:161049873:T:C	L534P	1.000
6:161049877:G:C	K535N	1.000
6:161049877:G:T	K535N	1.000
6:161049884:G:A	G538R	1.000
6:161049884:G:C	G538R	1.000
6:161049885:G:A	G538E	1.000
6:161049909:T:C	L546P	1.000
6:161070792:T:C	L631P	1.000
6:161070839:A:C	S647R	1.000
6:161070841:T:A	S647R	1.000
6:161070841:T:G	S647R	1.000
6:161073467:T:C	L651P	1.000
6:161073491:T:C	L659P	1.000
6:161080971:T:A	W730R	1.000
6:161080971:T:C	W730R	1.000
6:161092091:T:A	W1073R	1.000
6:161092091:T:C	W1073R	1.000
6:161092979:T:A	W1091R	1.000
6:161092979:T:C	W1091R	1.000
6:161092981:G:C	W1091C	1.000
6:161092981:G:T	W1091C	1.000
6:161092991:G:A	G1095R	1.000
6:161092991:G:C	G1095R	1.000
6:161093810:T:A	V1129D	1.000
6:161106678:T:C	F1341L	1.000

dbSNP variants (sampled 300 via entrez): RS1000004389 (6:161111196 G>A), RS1000016481 (6:161069883 G>A), RS1000021181 (6:161012068 G>A,C), RS1000044829 (6:161026846 T>C), RS1000054859 (6:160999295 G>A), RS1000090424 (6:161045398 G>A,T), RS1000107790 (6:161000379 G>T), RS1000117777 (6:161105739 G>A), RS1000128672 (6:161005406 C>A), RS1000189346 (6:161045492 T>C), RS1000207956 (6:161021619 C>A,G,T), RS1000218542 (6:161106073 G>C), RS1000277 (6:161105793 G>A,C), RS1000313210 (6:161062842 G>A), RS1000314910 (6:161112038 T>C)

Disease associations

OMIM: gene MIM:602425 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001599_4	Aging	3.000000e-06
GCST003075_128	Cognitive decline rate in late mild cognitive impairment	2.000000e-06
GCST003075_34	Cognitive decline rate in late mild cognitive impairment	7.000000e-07
GCST003127_16	Lipoprotein (a) levels	7.000000e-23
GCST004369_1	Ovarian disease with few adhesions	6.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0007710	cognitive decline measurement
EFO:0006925	lipoprotein A measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4853 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 199,752 (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
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL475251	R-406	2	762
CHEMBL564829	MILCICLIB	2	821
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL587723	AEE-788	2	2,697
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1090479	GSK-1070916	1	177
CHEMBL1908397	KW-2449	1	622
CHEMBL259084	MLN-8054	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — STE11 family

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
CI-1033	KD	1700 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM

ChEMBL bioactivities

45 potent at pChembl≥5 of 45 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.47	Kd	33.59	nM	CHEMBL5653589
7.41	Kd	39	nM	NERATINIB
7.30	ED50	50.01	nM	CHEMBL5653589
7.28	Kd	52	nM	ADAVOSERTIB
7.25	Kd	56	nM	CHEMBL386051
6.96	Kd	110	nM	BOSUTINIB
6.89	Kd	130	nM	PELITINIB
6.55	Kd	280	nM	PELITINIB
6.51	Kd	310	nM	DASATINIB
6.43	Kd	369	nM	PELITINIB
6.08	Kd	840	nM	R-406
6.05	Kd	885	nM	NERATINIB
5.92	Kd	1200	nM	STAUROSPORINE
5.84	Kd	1431	nM	GSK-1070916
5.84	Kd	1437	nM	ENCORAFENIB
5.80	Kd	1600	nM	KW-2449
5.79	Kd	1636	nM	BOSUTINIB
5.75	Kd	1800	nM	PHA-665752
5.72	Kd	1887	nM	MLN-8054
5.72	Kd	1900	nM	FORETINIB
5.70	Kd	2000	nM	CANERTINIB
5.70	Kd	2000	nM	TAE-684
5.66	Kd	2200	nM	STAUROSPORINE
5.66	Kd	2189	nM	AEE-788
5.60	Kd	2500	nM	TOZASERTIB
5.58	Kd	2600	nM	LESTAURTINIB
5.52	Kd	3000	nM	VANDETANIB
5.48	Kd	3300	nM	SUNITINIB
5.40	Kd	4021	nM	MILCICLIB
5.39	Kd	4100	nM	FEDRATINIB
5.32	Kd	4800	nM	VANDETANIB
5.32	Kd	4800	nM	SUNITINIB
5.27	Kd	5332	nM	CHEMBL3752910
5.26	Kd	5500	nM	DOVITINIB
5.25	Kd	5600	nM	AXITINIB
5.24	IC50	5800	nM	CHEMBL4756586
5.17	Kd	6700	nM	CHEMBL1908395
5.10	ED50	7939	nM	CHEMBL3752910
5.08	Kd	8400	nM	CANERTINIB

PubChem BioAssay actives

43 with measured affinity, of 510 total; 29 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148693: Binding affinity to human MAP3K4 incubated for 45 mins by Kinobead based pull down assay	kd	0.0336	uM
Neratinib	625027: Binding constant for MAP3K4 kinase domain	kd	0.0390	uM
1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1425048: 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	0.0520	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625027: Binding constant for MAP3K4 kinase domain	kd	0.0560	uM
Bosutinib	625027: Binding constant for MAP3K4 kinase domain	kd	0.1100	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256564: Average Binding Constant for MAP3K4; NA=Not Active at 10 uM	kd	0.1300	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435530: Binding constant for MAP3K4 kinase domain	kd	0.3100	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	625027: Binding constant for MAP3K4 kinase domain	kd	0.8400	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	435530: Binding constant for MAP3K4 kinase domain	kd	1.2000	uM
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethylpyrazol-3-yl]phenyl]-1,1-dimethylurea	1425048: 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	1.4310	uM
Encorafenib	1425048: 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	1.4370	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625027: Binding constant for MAP3K4 kinase domain	kd	1.6000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625027: Binding constant for MAP3K4 kinase domain	kd	1.8000	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	1425048: 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	1.8870	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	625027: Binding constant for MAP3K4 kinase domain	kd	1.9000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	256564: Average Binding Constant for MAP3K4; NA=Not Active at 10 uM	kd	2.0000	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	625027: Binding constant for MAP3K4 kinase domain	kd	2.0000	uM
6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1425048: 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	2.1890	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435530: Binding constant for MAP3K4 kinase domain	kd	2.5000	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	507600: Binding affinity to MAP3K4	kd	2.6000	uM
Vandetanib	625027: Binding constant for MAP3K4 kinase domain	kd	3.0000	uM
Sunitinib	256564: Average Binding Constant for MAP3K4; NA=Not Active at 10 uM	kd	3.3000	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1425048: 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	4.0210	uM
Fedratinib	625027: Binding constant for MAP3K4 kinase domain	kd	4.1000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148693: Binding affinity to human MAP3K4 incubated for 45 mins by Kinobead based pull down assay	kd	5.3322	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435530: Binding constant for MAP3K4 kinase domain	kd	5.5000	uM
Axitinib	625027: Binding constant for MAP3K4 kinase domain	kd	5.6000	uM
5-amino-N-[[4-[[(2S)-4-cyclohexyl-1-(ethylamino)-1-oxobutan-2-yl]carbamoyl]phenyl]methyl]-1-phenylpyrazole-4-carboxamide	1706602: Inhibition of C-terminal NanoLuc-fused full length MAP3K4 (unknown origin) expressed in HEK293T cells after 2 hrs by NanoBRET assay	ic50	5.8000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625027: Binding constant for MAP3K4 kinase domain	kd	6.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	6
Tobacco Smoke Pollution	increases expression	4
Particulate Matter	decreases expression, increases abundance, affects expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
Estradiol	increases expression, increases reaction, affects cotreatment	2
Progesterone	affects cotreatment, increases expression	2
Quercetin	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	decreases reaction, affects binding	1
tetrabromobisphenol A	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
calfactant	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Aerosols	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1

ChEMBL screening assays

131 unique, capped per target: 131 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037968	Binding	Binding affinity to human MAP3K4 at 200 nM by cell-based competition binding assay relative to control in presence of DTT	Staurosporine tethered peptide ligands that target cAMP-dependent protein kinase (PKA): optimization and selectivity profiling. — Bioorg Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1NM	Abcam K-562 MAP3K4 KO	Cancer cell line	Female
CVCL_D2K8	Abcam Raji MAP3K4 KO	Cancer cell line	Male
CVCL_D8Q2	Ubigene HCT 116 MAP3K4 KO	Cancer cell line	Male
CVCL_D9JE	Ubigene HEK293 MAP3K4 KO	Transformed cell line	Female
CVCL_SW68	HAP1 MAP3K4 (-) 1	Cancer cell line	Male
CVCL_SW69	HAP1 MAP3K4 (-) 2	Cancer cell line	Male
CVCL_SW70	HAP1 MAP3K4 (-) 3	Cancer cell line	Male
CVCL_UQ89	Abcam Jurkat MAP3K4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists