MAP3K20

Summary

MAP3K20 (mitogen-activated protein kinase kinase kinase 20, HGNC:17797) is a protein-coding gene on chromosome 2q31.1, encoding Mitogen-activated protein kinase kinase kinase 20 (Q9NYL2). Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation.

This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 51776 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy, centronuclear, 6, with fiber-type disproportion (Strong, ClinGen) — +4 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 456 total — 11 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 93
• Druggable target: yes — 53 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17797
Approved symbol	MAP3K20
Name	mitogen-activated protein kinase kinase kinase 20
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	MLTKalpha, MLTKbeta, ZAK, MLTK, MLK7, MRK
Ensembl gene	ENSG00000091436
Ensembl biotype	protein_coding
OMIM	609479
Entrez	51776

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000338983, ENST00000375213, ENST00000409176, ENST00000422149, ENST00000468408, ENST00000476618, ENST00000480606, ENST00000539448, ENST00000893700, ENST00000893701, ENST00000893702, ENST00000893703, ENST00000893704, ENST00000893705, ENST00000893706, ENST00000965866, ENST00000965867, ENST00000965868, ENST00000965869, ENST00000965870

RefSeq mRNA: 2 — MANE Select: NM_016653 NM_016653, NM_133646

CCDS: CCDS2251, CCDS42777

Canonical transcript exons

ENST00000375213 — 20 exons

Exon	Start	End
ENSE00000782376	173209729	173209835
ENSE00000882814	173217115	173217250
ENSE00001466194	173266050	173268015
ENSE00001466196	173263745	173263895
ENSE00001466198	173261063	173261137
ENSE00001466200	173258699	173258815
ENSE00001466202	173239404	173239496
ENSE00001466203	173238373	173238435
ENSE00001466205	173232320	173232459
ENSE00001466209	173232192	173232222
ENSE00001466212	173229689	173229733
ENSE00001926295	173075846	173076002
ENSE00003524804	173203796	173203870
ENSE00003547352	173190895	173190923
ENSE00003550475	173169805	173169892
ENSE00003558383	173191040	173191177
ENSE00003593994	173090998	173091190
ENSE00003602418	173182854	173182955
ENSE00003674649	173198026	173198112
ENSE00003790591	173187558	173187623

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2669 / max 443.1959, expressed in 1800 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23749	20.9732	1795
23751	3.0355	1311
23752	1.1991	778
23750	0.8523	533
23755	0.7079	201
23767	0.6889	112
23765	0.6437	48
23748	0.4121	207
23764	0.1878	29
23754	0.1663	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.70	gold quality
biceps brachii	UBERON:0001507	99.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.62	gold quality
body of tongue	UBERON:0011876	99.38	gold quality
saphenous vein	UBERON:0007318	99.15	gold quality
cauda epididymis	UBERON:0004360	99.02	gold quality
vena cava	UBERON:0004087	98.77	gold quality
urethra	UBERON:0000057	98.75	gold quality
seminal vesicle	UBERON:0000998	98.42	gold quality
synovial joint	UBERON:0002217	98.19	gold quality
pericardium	UBERON:0002407	98.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.80	gold quality
mucosa of stomach	UBERON:0001199	97.75	gold quality
gastrocnemius	UBERON:0001388	97.64	gold quality
superficial temporal artery	UBERON:0001614	97.60	gold quality
muscle of leg	UBERON:0001383	97.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.86	gold quality
lower esophagus	UBERON:0013473	96.81	gold quality
nipple	UBERON:0002030	96.79	gold quality
pylorus	UBERON:0001166	96.76	gold quality
parietal pleura	UBERON:0002400	96.69	gold quality
visceral pleura	UBERON:0002401	96.66	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.52	gold quality
buccal mucosa cell	CL:0002336	96.37	gold quality
penis	UBERON:0000989	96.24	gold quality
pharyngeal mucosa	UBERON:0000355	96.21	gold quality
tongue	UBERON:0001723	96.20	gold quality
mammary duct	UBERON:0001765	95.87	gold quality
cardiac ventricle	UBERON:0002082	95.79	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	43.26
E-GEOD-135922	yes	30.44
E-MTAB-8410	yes	23.78
E-GEOD-125970	yes	13.06
E-CURD-46	yes	9.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting MAP3K20, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6794-5P	99.76	66.38	1048

Literature-anchored findings (GeneRIF, showing 28)

• Results suggest that ZAK might play a role as an upstream signal to suppress the ZZaPK function and decrease E2F expression. (PMID:12535642)
• Data show that in response to radiation, MRK controls two independent pathways: the Chk2-Cdc25A pathway leading to cell cycle arrest and the p38gamma MAPK pathway (PMID:15342622)
• Results suggest that a ZAK mediates TGF-beta-induced cardiac hypertrophic growth via a novel TGF-beta signaling pathway. (PMID:15465036)
• ZAK induces characteristic hypertrophic growth features, including increased cell size, elevated atrial natriuretic factor expression, and increased actin fiber organization (PMID:15485649)
• Mixed lineage kinase 7 (MLK7), a splice variant of the ZAK gene, encodes an isoform which is the MAPKKK required for modulation of the stress-activated MAPKs downstream of anisomycin and UV stimulation. (PMID:15737997)
• data demonstrate that a ZAK isoform(s) is the MAP3Kinase that transduces the ribotoxic stress response (PMID:18331592)
• decrease of lung cancer cell proliferation by ZAK may involve the ERK and JNK pathways via an AP-1 transcription factor. (PMID:20331627)
• In this study, by applying a novel method, we have identified the phosphorylation sites in human MSK1 mitogen- and stress-activated protein kinase 1, and show that MRK-beta could also activate MSK1 through direct interaction. (PMID:20408143)
• The genes identified KTN1, ROCK1, and ZAK may be responsible for loss of cellular homeostasis in giant cells tumors of bone (PMID:21305317)
• MRK is a novel RhoC effector that controls LPA-stimulated cell invasion at least in part by regulating myosin dynamics, ERK and p38 (PMID:23319595)
• we report that sorafenib suppresses UV-induced apoptosis specifically by inhibiting c-jun-NH(2)-kinase (JNK) activation through the off-target inhibition of leucine zipper and sterile alpha motif-containing kinase (ZAK) (PMID:24170769)
• ZAK kinase isoform TV1 is preferentially upregulated in gastric tumours and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder and breast cancers. (PMID:24807215)
• The long non-coding RNA URHC promotes cell proliferation and inhibits apoptosis by repressing ZAK expression through inactivation of the ERK/MAPK pathway. (PMID:25013376)
• Gene set enrichment analysis disclosed a significant correlation between ZAK+ colorectal premalignant lesions and gene sets belonging to the MAPK/ERK and motility-related signaling pathways of the reactome database, strongly suggesting that ZAK induces such pro-tumoral reaction cascades in human cancers. (PMID:26522728)
• ZAK is a key player in mammalian limb patterning in humans and mice. (PMID:26755636)
• Recessive mutations in the kinase ZAK - novel cause of congenital myopathy. (PMID:27816943)
• The ZAK rs3769201 and rs722864 may be functional susceptibility loci for lung cancer risk. (PMID:29071797)
• promoting epithelial mesenchymal transition is the primary role for ZAK in cancer progression. (PMID:29396440)
• The expression of ZAKbeta is dependent on ZAKalpha expression, and ZAKbeta further enhances ZAKalpha expression and results in synergistic enhancement of apoptosis in osteosarcoma cells. (PMID:29654619)
• MLK7AS1 has potential as a biomarker and may promote proliferation in CRC partially through downregulating p21 expression. (PMID:30535460)
• miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3. (PMID:30765768)
• Selective Activation of ZAK beta Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation. (PMID:32397561)
• MicroRNA-335 inhibits the growth, chemo-sensitivity, and metastasis of human breast cancer cells by targeting MAP3K2. (PMID:32521851)
• ZAK Gene Expression in Patients with Helicobacter pylori Infection. (PMID:33620708)
• Targeted inhibition of ZAK ameliorates renal interstitial fibrosis. (PMID:35276386)
• ZAKalpha-driven ribotoxic stress response activates the human NLRP1 inflammasome. (PMID:35857590)
• Myofibrillar myopathy hallmarks associated with ZAK deficiency. (PMID:37427997)
• Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies. (PMID:38451290)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	map3k20a	ENSDARG00000006978
mus_musculus	Map3k20	ENSMUSG00000004085
rattus_norvegicus	Map3k20	ENSRNOG00000001515
caenorhabditis_elegans		WBGENE00006971

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TESK1 (ENSG00000107140), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), MAP3K10 (ENSG00000130758), RAF1 (ENSG00000132155), RIPK1 (ENSG00000137275), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), ILK (ENSG00000166333), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MOS (ENSG00000172680), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase 20 — Q9NYL2 (reviewed: Q9NYL2)

Alternative names: Human cervical cancer suppressor gene 4 protein, Leucine zipper- and sterile alpha motif-containing kinase, MLK-like mitogen-activated protein triple kinase, Mitogen-activated protein kinase kinase kinase MLT, Mixed lineage kinase 7, Mixed lineage kinase-related kinase, Sterile alpha motif- and leucine zipper-containing kinase AZK

All UniProt accessions (3): Q9NYL2, C9J3F7, D4Q8H0

UniProt curated annotations — full annotation on UniProt →

Function. Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation. Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JNK (MAPK8/JNK1, MAPK9/JNK2 and/or MAPK10/JNK3) and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways. Activates JNK through phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7, and MAP kinase p38 gamma (MAPK12) via phosphorylation of MAP2K3/MKK3 and MAP2K6/MKK6. Involved in stress associated with adrenergic stimulation: contributes to cardiac decompensation during periods of acute cardiac stress. May be involved in regulation of S and G2 cell cycle checkpoint by mediating phosphorylation of CHEK2. Key component of the stress-activated protein kinase signaling cascade in response to ribotoxic stress or UV-B irradiation. Acts as the proximal sensor of ribosome collisions during the ribotoxic stress response (RSR): directly binds to the ribosome by inserting its flexible C-terminus into the ribosomal intersubunit space, thereby acting as a sentinel for colliding ribosomes. Upon ribosome collisions, activates either the stress-activated protein kinase signal transduction cascade or the integrated stress response (ISR), leading to programmed cell death or cell survival, respectively. Dangerous levels of ribosome collisions trigger the autophosphorylation and activation of MAP3K20, which dissociates from colliding ribosomes and phosphorylates MAP kinase kinases, leading to activation of the JNK and MAP kinase p38 pathways that promote programmed cell death. Less dangerous levels of ribosome collisions trigger the integrated stress response (ISR): MAP3K20 activates EIF2AK4/GCN2 independently of its protein-kinase activity, promoting EIF2AK4/GCN2-mediated phosphorylation of EIF2S1/eIF-2-alpha. Also part of the stress-activated protein kinase signaling cascade triggering the NLRP1 inflammasome in response to UV-B irradiation: ribosome collisions activate MAP3K20, which directly phosphorylates NLRP1, leading to activation of the NLRP1 inflammasome and subsequent pyroptosis. NLRP1 is also phosphorylated by MAP kinase p38 downstream of MAP3K20. Also acts as a histone kinase by phosphorylating histone H3 at ‘Ser-28’ (H3S28ph). Isoform that lacks the C-terminal region that mediates ribosome-binding: does not act as a sensor of ribosome collisions in response to ribotoxic stress. May act as an antagonist of isoform ZAKalpha: interacts with isoform ZAKalpha, leading to decrease the expression of isoform ZAKalpha.

Subunit / interactions. Homodimer. Interacts with ZNF33A. Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, MAP3K20 and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and MAP3K20. Interacts with EIF2AK4/GCN2; promoting EIF2AK4/GCN2 kinase activity. Interacts with isoform ZAKbeta. Interacts with isoform ZAKalpha.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed. Isoform ZAKbeta is the predominant form in all tissues examined, except for liver, in which isoform ZAKalpha is more highly expressed.

Post-translational modifications. Activated by phosphorylation by PKN1, followed by autophosphorylation on Thr-161 and Ser-165. Autophosphorylation in response to ribotoxic stress promotes dissociation from colliding ribosomes and activation.

Disease relevance. Split-foot malformation with mesoaxial polydactyly (SFMMP) [MIM:616890] An autosomal recessive disorder characterized by a split-foot defect, mesoaxial polydactyly, nail abnormalities of the hands, and sensorineural hearing loss. The disease is caused by variants affecting the gene represented in this entry. Myopathy, centronuclear, 6, with fiber-type disproportion (CNM6) [MIM:617760] A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal recessive, slowly progressive form with onset in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated in response to stress, such as ribosomal stress, osmotic shock and ionizing radiation. Activated by phosphorylation by PKN1, followed by autophosphorylation on Thr-161 and Ser-165. Inhibited by nilotinib, sorafenib, dabrafenib, rebastinib and vemurafenib. Selectively inhibited by N-(3)-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamide compound 3h. Selectively inhibited by 1,2,3-triazole benzenesulfonamides.

Domain organisation. Recognizes stalled ribosomes via two separate and partially redundant sensor domains: the C-terminal domain (CTD) that binds the 18S ribosomal RNA (18S rRNA) and the sensing domain (S).

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NYL2-1	ZAKalpha, Alpha	yes
Q9NYL2-2	ZAKbeta, Beta, MLK7
Q9NYL2-3	3, HCCS-4

RefSeq proteins (2): NP_057737, NP_598407 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001660	SAM	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR051681	Ser/Thr_Kinases-Pseudokinases	Family

Pfam: PF07647, PF07714

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 (102 total): modified residue 30, helix 18, sequence variant 13, strand 9, compositionally biased region 7, mutagenesis site 6, region of interest 4, splice variant 4, turn 3, binding site 2, domain 2, initiator methionine 1, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5X5O	X-RAY DIFFRACTION	1.87
6JUU	X-RAY DIFFRACTION	1.9
6JUT	X-RAY DIFFRACTION	2.1
7YAW	X-RAY DIFFRACTION	2.1
5HES	X-RAY DIFFRACTION	2.14
9RPV	ELECTRON MICROSCOPY	2.35
7YAZ	X-RAY DIFFRACTION	2.54
9RSX	ELECTRON MICROSCOPY	2.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYL2-F1	69.15	0.31

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): 133 (proton acceptor)

Ligand- & substrate-binding residues (2): 22–30; 45

Post-translational modifications (30): 434, 454, 2, 2, 3, 7, 161, 165, 275, 302, 567, 586, 587, 593, 599, 628, 633, 637, 648, 649 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
45	loss of kinase activity. does not affect ability to activate eif2ak4/gcn2 in response to mild ribosome collision.
161	loss of autophosphorylation activity.
162	slight loss of autophosphorylation activity.
165	loss of autophosphorylation activity.
657	abolished association with btrc without affecting protein stability.
752–761	mimics phosphorylation; impaired ribosome-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 587 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_TRANSLATION_IN_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_INFLAMMATORY_RESPONSE, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_GAMMA_RADIATION, KEGG_TIGHT_JUNCTION

GO Biological Process (29): DNA damage checkpoint signaling (GO:0000077), MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), inflammatory response (GO:0006954), cytoskeleton organization (GO:0007010), chromosome segregation (GO:0007059), JNK cascade (GO:0007254), cell death (GO:0008219), regulation of mitotic metaphase/anaphase transition (GO:0030071), cell differentiation (GO:0030154), stress-activated protein kinase signaling cascade (GO:0031098), p38MAPK cascade (GO:0038066), embryonic digit morphogenesis (GO:0042733), positive regulation of apoptotic process (GO:0043065), positive regulation of programmed cell death (GO:0043068), protein autophosphorylation (GO:0046777), stress-activated MAPK cascade (GO:0051403), limb development (GO:0060173), pyroptotic inflammatory response (GO:0070269), negative regulation of stress-activated protein kinase signaling cascade (GO:0070303), cellular response to gamma radiation (GO:0071480), cellular response to UV-B (GO:0071493), GCN2-mediated signaling (GO:0140469), negative regulation of translation in response to endoplasmic reticulum stress (GO:1902010), positive regulation of mitotic DNA damage checkpoint (GO:1904291), translational initiation (GO:0006413), intracellular signal transduction (GO:0035556), protein maturation (GO:0051604), NLRP1 inflammasome complex assembly (GO:1904784)

GO Molecular Function (19): magnesium ion binding (GO:0000287), RNA binding (GO:0003723), protein serine/threonine kinase activity (GO:0004674), JUN kinase kinase kinase activity (GO:0004706), MAP kinase kinase kinase activity (GO:0004709), ATP binding (GO:0005524), protein kinase activator activity (GO:0030295), ribosome binding (GO:0043022), small ribosomal subunit rRNA binding (GO:0070181), protein serine kinase activity (GO:0106310), stalled ribosome sensor activity (GO:0170011), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), rRNA binding (GO:0019843), protein kinase regulator activity (GO:0019887), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
MAPK cascade	4
protein kinase activity	4
stress-activated protein kinase signaling cascade	2
cellular anatomical structure	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
defense response	1
organelle organization	1
cell cycle process	1
cellular process	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of metaphase/anaphase transition of cell cycle	1
cellular developmental process	1
cellular response to stress	1
intracellular signal transduction	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
programmed cell death	1
regulation of programmed cell death	1
positive regulation of cellular process	1
protein phosphorylation	1
appendage development	1
inflammatory response	1
regulation of stress-activated protein kinase signaling cascade	1
negative regulation of intracellular signal transduction	1
metal ion binding	1
nucleic acid binding	1
MAP kinase kinase kinase activity	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase activator activity	1
protein kinase regulator activity	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP3K20	PKN1	Q16512	939
MAP3K20	MAP2K3	P46734	938
MAP3K20	ZNF33A	P17013	668
MAP3K20	MAPK14	Q16539	656
MAP3K20	NPPA	P01160	440
MAP3K20	LYN	P07948	401
MAP3K20	LCK	P06239	385
MAP3K20	BMX	P51813	371
MAP3K20	AKAP13	Q12802	371
MAP3K20	EPHA3	P29320	363
MAP3K20	MS4A2	Q01362	355
MAP3K20	AARS1	P49588	354
MAP3K20	APPL1	Q9UKG1	342
MAP3K20	SCLT1	Q96NL6	333
MAP3K20	FLT3	P36888	326

IntAct

119 interactions, top by confidence:

A	B	Type	Score
YWHAZ	MAP3K20	psi-mi:“MI:0915”(physical association)	0.860
YWHAZ	MAP3K20	psi-mi:“MI:0403”(colocalization)	0.860
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
ZNF567	MAP3K20	psi-mi:“MI:0915”(physical association)	0.670
MAP3K20	ZNF567	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
MAP3K20	RPS6KA5	psi-mi:“MI:0915”(physical association)	0.600
RPS6KA5	MAP3K20	psi-mi:“MI:0915”(physical association)	0.600
RPS6KA5	MAP3K20	psi-mi:“MI:0403”(colocalization)	0.600
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SFN	MAP3K20	psi-mi:“MI:0915”(physical association)	0.540
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ZNF544	GNPAT	psi-mi:“MI:0914”(association)	0.530
ZNF71	NVL	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
MAP3K20	MAP3K20	psi-mi:“MI:0192”(acetylation reaction)	0.440

BioGRID (132): ZFP2 (Two-hybrid), ZNF567 (Two-hybrid), ZNF567 (Two-hybrid), ZAK (Biochemical Activity), ZAK (Two-hybrid), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS), ZAK (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

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

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MAP3K20	up-regulates	MAP3K20	phosphorylation
PKN1	up-regulates	MAP3K20	phosphorylation
MAP3K20	“up-regulates activity”	MAP2K7	phosphorylation
MAP3K20	“up-regulates activity”	MAP2K4	phosphorylation
MAP3K20	“down-regulates activity”	ARHGDIB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	60.6×	2e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	53.4×	4e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	53.4×	4e-09
Activation of BH3-only proteins	7	39.5×	2e-08
RHO GTPases activate PKNs	8	28.8×	2e-08
Intrinsic Pathway for Apoptosis	7	23.3×	9e-07
FOXO-mediated transcription	5	19.1×	2e-04
SARS-CoV-1-host interactions	9	18.0×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	20.0×	4e-04
intracellular protein localization	9	8.6×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	2
Uncertain significance	148
Likely benign	211
Benign	45

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1377427	NM_016653.3(MAP3K20):c.1357C>T (p.Gln453Ter)	Pathogenic
1455550	NM_016653.3(MAP3K20):c.1313_1343dup (p.Pro452fs)	Pathogenic
1702967	NM_016653.3(MAP3K20):c.1592C>A (p.Ser531Ter)	Pathogenic
2000650	NC_000002.12:g.173263743AG[1]	Pathogenic
2105146	NM_016653.3(MAP3K20):c.1601G>A (p.Trp534Ter)	Pathogenic
218144	NM_016653.3(MAP3K20):c.1103T>G (p.Phe368Cys)	Pathogenic
224905	NM_016653.2(MAP3K20):c.988-4814_1359+60del	Pathogenic
2695259	NM_016653.3(MAP3K20):c.549_550del (p.Ser184fs)	Pathogenic
3728574	NM_016653.3(MAP3K20):c.591G>A (p.Trp197Ter)	Pathogenic
446158	NM_016653.3(MAP3K20):c.490_491del (p.Met164fs)	Pathogenic
446159	NM_016653.3(MAP3K20):c.515G>A (p.Trp172Ter)	Pathogenic
1327113	NM_016653.3(MAP3K20):c.834CAA[1] (p.Asn279del)	Likely pathogenic
1928902	NM_016653.3(MAP3K20):c.1476+2T>A	Likely pathogenic

SpliceAI

3082 predictions. Top by Δscore:

Variant	Effect	Δscore
2:173090993:TGCAG:T	acceptor_loss	1.0000
2:173090996:A:AG	acceptor_gain	1.0000
2:173090996:A:G	acceptor_loss	1.0000
2:173090997:G:GT	acceptor_gain	1.0000
2:173090997:GA:G	acceptor_gain	1.0000
2:173090997:GAT:G	acceptor_gain	1.0000
2:173090997:GATT:G	acceptor_gain	1.0000
2:173090997:GATTT:G	acceptor_gain	1.0000
2:173091152:G:GT	donor_gain	1.0000
2:173091188:GAG:G	donor_gain	1.0000
2:173091192:T:G	donor_loss	1.0000
2:173169803:A:AG	acceptor_gain	1.0000
2:173169804:G:GG	acceptor_gain	1.0000
2:173169804:GGCA:G	acceptor_gain	1.0000
2:173169890:CAGGT:C	donor_loss	1.0000
2:173169891:AGGTA:A	donor_loss	1.0000
2:173169893:G:GA	donor_loss	1.0000
2:173169893:G:GG	donor_gain	1.0000
2:173169894:T:A	donor_loss	1.0000
2:173182847:A:AG	acceptor_gain	1.0000
2:173182848:A:G	acceptor_gain	1.0000
2:173182852:A:AG	acceptor_gain	1.0000
2:173182853:G:GG	acceptor_gain	1.0000
2:173182853:GA:G	acceptor_gain	1.0000
2:173182853:GAAT:G	acceptor_gain	1.0000
2:173182951:CAAAG:C	donor_loss	1.0000
2:173182952:AAAGG:A	donor_loss	1.0000
2:173182953:AAGGT:A	donor_loss	1.0000
2:173182956:GTA:G	donor_loss	1.0000
2:173182957:T:G	donor_loss	1.0000

AlphaMissense

5300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:173091104:G:A	G25R	1.000
2:173091104:G:C	G25R	1.000
2:173091105:G:A	G25E	1.000
2:173091110:T:C	F27L	1.000
2:173091112:T:A	F27L	1.000
2:173091112:T:G	F27L	1.000
2:173091113:G:A	G28R	1.000
2:173091113:G:C	G28R	1.000
2:173091113:G:T	G28W	1.000
2:173091114:G:A	G28E	1.000
2:173091120:T:A	V30D	1.000
2:173091126:G:C	R32P	1.000
2:173091128:G:C	A33P	1.000
2:173091129:C:A	A33D	1.000
2:173091134:T:A	W35R	1.000
2:173091134:T:C	W35R	1.000
2:173091159:C:A	A43D	1.000
2:173091162:T:A	V44E	1.000
2:173091164:A:G	K45E	1.000
2:173091166:G:C	K45N	1.000
2:173091166:G:T	K45N	1.000
2:173169815:T:C	L57P	1.000
2:173169853:G:A	G70R	1.000
2:173169853:G:C	G70R	1.000
2:173169854:G:A	G70E	1.000
2:173169854:G:T	G70V	1.000
2:173169887:T:A	V81D	1.000
2:173187599:C:G	H131D	1.000
2:173187603:G:C	R132T	1.000
2:173187603:G:T	R132I	1.000

dbSNP variants (sampled 300 via entrez): RS1000010561 (2:173172479 C>T), RS1000025659 (2:173263103 T>C), RS1000033607 (2:173262598 CAAAAAAGAAAAA>C), RS1000035538 (2:173184344 C>T), RS1000035729 (2:173209180 C>T), RS1000069267 (2:173173622 T>A), RS1000084344 (2:173219103 A>G), RS1000086446 (2:173115917 A>G), RS1000094486 (2:173144469 AAAAAAAAAAAAAAAAAG>A), RS1000131823 (2:173127943 A>C,G), RS1000152259 (2:173119401 A>C), RS1000158655 (2:173225444 A>C), RS1000189602 (2:173246034 T>C), RS1000221154 (2:173212539 C>G,T), RS1000232260 (2:173084174 G>A)

Disease associations

OMIM: gene MIM:609479 | disease phenotypes: MIM:616890, MIM:617760, MIM:183600, MIM:160150

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy, centronuclear, 6, with fiber-type disproportion	Strong	Autosomal recessive
syndromic disease	Strong	Autosomal dominant
split hand-foot malformation	Moderate	Autosomal dominant
congenital fiber-type disproportion myopathy	Supportive	Autosomal dominant
split-foot malformation-mesoaxial polydactyly syndrome	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
myopathy, centronuclear, 6, with fiber-type disproportion	Strong	AR

Mondo (7): split-foot malformation-mesoaxial polydactyly syndrome (MONDO:0014816), myopathy, centronuclear, 6, with fiber-type disproportion (MONDO:0054695), split hand-foot malformation 1 (MONDO:0008464), centronuclear myopathy (MONDO:0018947), split hand-foot malformation (MONDO:0016576), congenital fiber-type disproportion myopathy (MONDO:0009711), syndromic disease (MONDO:0002254)

Orphanet (3): Split-foot malformation-mesoaxial polydactyly syndrome (Orphanet:488232), Isolated split hand-split foot malformation (Orphanet:2440), Centronuclear myopathy (Orphanet:595)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000602	Ophthalmoplegia
HP:0000678	Dental crowding
HP:0000767	Pectus excavatum
HP:0001171	Split hand
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001315	Reduced tendon reflexes
HP:0001371	Flexion contracture
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001597	Abnormal nail morphology
HP:0001609	Hoarse voice
HP:0001627	Abnormal heart morphology
HP:0001648	Cor pulmonale
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001824	Weight loss
HP:0001839	Split foot
HP:0002015	Dysphagia
HP:0002058	Myopathic facies
HP:0002086	Abnormality of the respiratory system

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003096_4	Adiponectin levels	2.000000e-06
GCST004748_72	Lung cancer	6.000000e-07
GCST006627_44	Diastolic blood pressure	2.000000e-11
GCST007327_201	Smoking status (ever vs never smokers)	5.000000e-08
GCST007576_222	Chronotype	2.000000e-09
GCST009416_3	Optic nerve head parameters (multi-trait analysis)	9.000000e-10
GCST009524_100	Household income (MTAG)	2.000000e-08
GCST010241_234	Apolipoprotein A1 levels	2.000000e-09
GCST90000047_77	Age at first sexual intercourse	2.000000e-15
GCST90014033_17	Haemorrhoidal disease	4.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0006336	diastolic blood pressure
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0009695	household income
EFO:0004614	apolipoprotein A 1 measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3886 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

53 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 457,446 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1229517	VEMURAFENIB	4	15,704
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL5416410	DASATINIB	4	655
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL941	IMATINIB	4	111,611
CHEMBL101253	VATALANIB	3	11,319
CHEMBL1908391	MASITINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL3186534	RIVOCERANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MLK subfamily

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

Ligand	Action	Affinity	Parameter
ZAK inhibitor 6p	Inhibition	8.4	pIC50
KC-130	Inhibition	7.94	pIC50
compound 15b [PMID: 16539403]	Inhibition	6.15	pIC50

Binding affinities (BindingDB)

12 measured of 12 human assays (12 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 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
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	KD	4500 nM

ChEMBL bioactivities

348 potent at pChembl≥5 of 355 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.72	IC50	1.9	nM	CHEMBL4524151
8.68	IC50	2.1	nM	CHEMBL4542865
8.64	IC50	2.3	nM	CHEMBL4526537
8.64	Kd	2.3	nM	AST-487
8.57	Kd	2.7	nM	CHEMBL4098896
8.52	IC50	3	nM	CHEMBL4574656
8.48	IC50	3.3	nM	CHEMBL4098896
8.48	IC50	3.3	nM	CHEMBL4579609
8.42	IC50	3.8	nM	CHEMBL4446003
8.40	IC50	4	nM	CHEMBL4450810
8.40	IC50	4	nM	VEMURAFENIB
8.38	IC50	4.2	nM	CHEMBL4096439
8.38	IC50	4.2	nM	CHEMBL4468296
8.36	IC50	4.4	nM	CHEMBL4454493
8.35	IC50	4.5	nM	CHEMBL4448690
8.30	IC50	5	nM	CHEMBL4080860
8.29	IC50	5.1	nM	CHEMBL4104859
8.29	IC50	5.1	nM	CHEMBL4091071
8.24	IC50	5.7	nM	CHEMBL4457930
8.20	Kd	6.3	nM	SORAFENIB
8.16	IC50	6.9	nM	CHEMBL4449013
8.12	IC50	7.5	nM	CHEMBL4079935
8.10	Kd	8	nM	CHEMBL4450810
8.10	Kd	8	nM	MOTESANIB
8.06	IC50	8.8	nM	CHEMBL4450810
8.05	IC50	8.9	nM	CHEMBL4559022
8.04	IC50	9.1	nM	CHEMBL5398699
8.02	IC50	9.6	nM	CHEMBL4088739
8.02	Kd	9.5	nM	CHEMBL4865410
8.00	IC50	10.1	nM	CHEMBL5395126
8.00	IC50	9.9	nM	CHEMBL5417718
8.00	IC50	10.1	nM	CHEMBL5437385
7.96	Kd	11	nM	NILOTINIB
7.94	IC50	11.5	nM	CHEMBL5436237
7.92	IC50	12.1	nM	CHEMBL4104171
7.91	IC50	12.3	nM	CHEMBL5413413
7.83	IC50	14.7	nM	CHEMBL4096439
7.80	Ki	15.85	nM	SORAFENIB
7.78	IC50	16.8	nM	CHEMBL4069195
7.72	IC50	19.2	nM	CHEMBL4080626
7.72	IC50	19	nM	CHEMBL4793380
7.65	IC50	22.6	nM	CHEMBL4060505
7.64	IC50	23	nM	VEMURAFENIB
7.61	IC50	24.7	nM	CHEMBL4476053
7.54	IC50	29	nM	CHEMBL4473008
7.50	IC50	31.4	nM	VEMURAFENIB
7.50	Ki	31.62	nM	CHEMBL1994938
7.46	IC50	34.7	nM	CHEMBL5411306
7.41	IC50	39	nM	LY-3009120
7.39	Kd	41	nM	PONATINIB

PubChem BioAssay actives

170 with measured affinity, of 1451 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
3-chloro-N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0019	uM
3-bromo-N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0021	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435941: Binding constant for ZAK kinase domain	kd	0.0023	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]-3-methoxybenzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0023	uM
3-cyano-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486187: Binding affinity to partial length human ZAK expressed in Escherichia coli BL21 by active-site-dependent competition assay	kd	0.0027	uM
3-chloro-N-[2-fluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0030	uM
3-cyano-N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0033	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0038	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]-3-phenylbenzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0040	uM
Vemurafenib	1974650: Inhibition of full-length human ZAK using MBP as substrate in presence off ATP by competitive binding assay	ic50	0.0040	uM
3-chloro-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0042	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]naphthalene-1-sulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0042	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]-3-methylbenzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0044	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]naphthalene-2-sulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0045	uM
3-bromo-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0050	uM
3-chloro-N-[2,4-difluoro-3-[2-(1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0051	uM
2-chloro-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0051	uM
3-chloro-N-[4-fluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0057	uM
Sorafenib	435941: Binding constant for ZAK kinase domain	kd	0.0063	uM
N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]-3-propan-2-ylbenzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0069	uM
N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]-3-methoxybenzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0075	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	435941: Binding constant for ZAK kinase domain	kd	0.0080	uM
N-[3-[4-(2-aminopyrimidin-5-yl)triazol-1-yl]-2,4-difluorophenyl]-3-chlorobenzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0089	uM
N-[3-[[5-[1-[2,6-difluoro-3-[(3-phenylphenyl)sulfonylamino]phenyl]triazol-4-yl]-1H-pyrazolo[5,4-b]pyridin-3-yl]oxy]propyl]prop-2-enamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0091	uM
N-[3-[5-(4-aminophenyl)-2H-pyrazolo[3,4-b]pyridine-3-carbonyl]-2,4-difluorophenyl]-1-phenylmethanesulfonamide	1753619: Binding affinity to wild-type human partial length ZAK (M1 to L331 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0095	uM
2,3-dichloro-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0096	uM
N-[2,4-difluoro-3-[4-[3-[(3S)-1-prop-2-enoylpyrrolidin-3-yl]oxy-1H-pyrazolo[5,4-b]pyridin-5-yl]triazol-1-yl]phenyl]-3-phenylbenzenesulfonamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0099	uM
N-[6-[4-[[5-[1-[2,6-difluoro-3-[(3-phenylphenyl)sulfonylamino]phenyl]triazol-4-yl]-1H-pyrazolo[5,4-b]pyridin-3-yl]oxymethyl]piperidin-1-yl]hexyl]prop-2-enamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0101	uM
N-[2,4-difluoro-3-[4-[3-(1-prop-2-enoylpyrrolidin-3-yl)oxy-1H-pyrazolo[5,4-b]pyridin-5-yl]triazol-1-yl]phenyl]benzenesulfonamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0101	uM
Nilotinib	624755: Binding constant for ZAK kinase domain	kd	0.0110	uM
N-[2,4-difluoro-3-[4-[3-(1-prop-2-enoylpyrrolidin-3-yl)oxy-1H-pyrazolo[5,4-b]pyridin-5-yl]triazol-1-yl]phenyl]-3-phenylbenzenesulfonamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0115	uM
N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]-3-methylbenzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0121	uM
N-[2,4-difluoro-3-[4-[3-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxy-1H-pyrazolo[5,4-b]pyridin-5-yl]triazol-1-yl]phenyl]-3-phenylbenzenesulfonamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0123	uM
4-chloro-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0168	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735642: Inhibition of recombinant full-length human ZAK using MBP as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	0.0190	uM
N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0192	uM
3-chloro-N-[2,4-difluoro-3-[2-(1H-pyrrolo[2,3-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0226	uM
3-chloro-N-[3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0247	uM
3-chloro-N-[2,4-difluoro-3-[5-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)-1,2,4-oxadiazol-3-yl]phenyl]benzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0290	uM
7-[[5-[1-[2,6-difluoro-3-[(3-phenylphenyl)sulfonylamino]phenyl]triazol-4-yl]-1H-pyrazolo[5,4-b]pyridin-3-yl]oxy]-N-(1-prop-2-enoylpiperidin-3-yl)heptanamide	1990324: Inhibition of recombinant ZAK (unknown origin) using ATP as substrate preincubated for 60 mins followed by substrate addition and measured after 40 mins by fluorescence based envision multilabel reader method	ic50	0.0347	uM
1-(3,3-dimethylbutyl)-3-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea	1226897: Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue	ic50	0.0390	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	624755: Binding constant for ZAK kinase domain	kd	0.0410	uM
Ponatinib	1425213: 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	0.0410	uM
3-chloro-N-[2,4-difluoro-3-[2-(3-propan-2-yloxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486184: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0427	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	435941: Binding constant for ZAK kinase domain	kd	0.0450	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	624755: Binding constant for ZAK kinase domain	kd	0.0450	uM
N-[3-[4-(6-amino-3-pyridinyl)triazol-1-yl]-2,4-difluorophenyl]-3-chlorobenzenesulfonamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0462	uM
6-[3-[(5-chloro-2-methoxy-3-pyridinyl)sulfonylamino]-2,6-difluorophenyl]-N-methylimidazo[1,5-a]pyrazine-1-carboxamide	2103379: Inhibition of ZAK in human MOLM16 cells	ic50	0.0470	uM
1-(3-chlorophenyl)-3-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]urea	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0530	uM
3-chloro-N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzamide	1557850: Inhibition of N-terminal GST-tagged recombinant human full-length ZAK expressed in baculovirus infected Sf9 insect cells using MBP as substrate after 30 mins by ADP-Glo assay	ic50	0.0543	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	6
trichostatin A	affects expression, affects cotreatment, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
XMU-MP-1	increases phosphorylation, decreases reaction, increases cleavage	1
myristicin	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases expression	1
arsenite	decreases reaction, affects binding	1
fisetin	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
cupric chloride	increases expression	1
quinoline	decreases reaction, increases activity, increases phosphorylation, increases reaction, decreases activity	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1

ChEMBL screening assays

245 unique, capped per target: 244 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1045675	Binding	Binding affinity to ZAK assessed as percentage of kinase remaining bound to the bead at 1 uM by T7 phage display based binding assay	Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). — J Med Chem
CHEMBL1963763	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ZAK	PubChem BioAssay data set

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B1WK	Abcam HeLa MAP3K20 KO	Cancer cell line	Female
CVCL_D9JD	Ubigene HEK293 MAP3K20 KO	Transformed cell line	Female
CVCL_E0H9	Ubigene HeLa MAP3K20 KO	Cancer cell line	Female
CVCL_TY49	HAP1 ZAK (-) 1	Cancer cell line	Male
CVCL_TY50	HAP1 ZAK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT00272883	Not specified	RECRUITING	Molecular and Genetic Studies of Congenital Myopathies
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome
NCT04033159	PHASE1/PHASE2	TERMINATED	Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies
NCT04743557	PHASE1/PHASE2	WITHDRAWN	Early Phase Human Drug Trial to Investigate DYN101 in Participants 2 to 17 Years With Centronuclear Myopathies
NCT03351270	Not specified	COMPLETED	Prospective Natural History Study of Patients With Myotubular Myopathy and Other CentroNuclear Myopathies
NCT04064307	Not specified	RECRUITING	Myotubular and Centronuclear Myopathy Patient Registry
NCT04977648	Not specified	WITHDRAWN	Natural History Study of Patients With Centronuclear Myopathies
NCT05099107	Not specified	COMPLETED	Changes of Motor Function Tests in Congenital Myopathy Subjects Treated With Oral Salbutamol as Compared to no Treatment
NCT05982119	Not specified	RECRUITING	Assessments in Patients With Muscular Pathology and in Control Subjects : The ActiLiège Next Study
NCT06157268	Not specified	RECRUITING	The Natural History and Muscle Fatigability of Patients With Congenital Myopathies.
NCT07021820	Not specified	RECRUITING	Multispectral Optoacoustic Tomography for Advanced Imaging of Centronuclear Myopathy
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease