MUSK

Summary

MUSK (muscle associated receptor tyrosine kinase, HGNC:7525) is a protein-coding gene on chromosome 9q31.3, encoding Muscle, skeletal receptor tyrosine-protein kinase (O15146). Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle.

This gene encodes a muscle-specific tyrosine kinase receptor. The encoded protein may play a role in clustering of the acetylcholine receptor in the postsynaptic neuromuscular junction. Mutations in this gene have been associated with congenital myasthenic syndrome. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 4593 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 9 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 902 total — 44 pathogenic, 34 likely-pathogenic
• Phenotypes (HPO): 136
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005592

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7525
Approved symbol	MUSK
Name	muscle associated receptor tyrosine kinase
Location	9q31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000030304
Ensembl biotype	protein_coding
OMIM	601296
Entrez	4593

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000189978, ENST00000374438, ENST00000374439, ENST00000374448, ENST00000416899, ENST00000634612

RefSeq mRNA: 3 — MANE Select: NM_005592 NM_001166280, NM_001166281, NM_005592

CCDS: CCDS48005, CCDS75874

Canonical transcript exons

ENST00000374448 — 15 exons

Exon	Start	End
ENSE00000719983	110784815	110785016
ENSE00000720010	110785527	110785718
ENSE00000720035	110787690	110787838
ENSE00000926843	110747641	110747800
ENSE00001034292	110776632	110776655
ENSE00001646804	110775788	110775963
ENSE00001669334	110762202	110762208
ENSE00001671992	110767820	110768083
ENSE00001678191	110697325	110697466
ENSE00001766374	110695403	110695530
ENSE00001790353	110734251	110734375
ENSE00003508946	110668791	110668983
ENSE00003745850	110687117	110687268
ENSE00003747403	110682674	110682800
ENSE00003889215	110800306	110806558

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 82.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9028 / max 90.2776, expressed in 155 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98000	0.4549	107
97999	0.3523	104
98001	0.0393	21
98002	0.0385	24
97998	0.0179	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.37	gold quality
mucosa of stomach	UBERON:0001199	79.71	gold quality
sural nerve	UBERON:0015488	76.60	gold quality
calcaneal tendon	UBERON:0003701	75.75	gold quality
colonic epithelium	UBERON:0000397	71.85	gold quality
right lung	UBERON:0002167	70.90	gold quality
gastrocnemius	UBERON:0001388	70.74	gold quality
corpus callosum	UBERON:0002336	70.52	gold quality
rectum	UBERON:0001052	69.68	gold quality
muscle of leg	UBERON:0001383	68.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.46	gold quality
small intestine	UBERON:0002108	66.53	gold quality
vermiform appendix	UBERON:0001154	65.37	gold quality
muscle organ	UBERON:0001630	65.27	gold quality
gall bladder	UBERON:0002110	65.27	gold quality
right atrium auricular region	UBERON:0006631	65.26	gold quality
caecum	UBERON:0001153	64.44	gold quality
tendon	UBERON:0000043	64.22	gold quality
cardiac atrium	UBERON:0002081	64.10	gold quality
vena cava	UBERON:0004087	63.91	gold quality
stomach	UBERON:0000945	61.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	61.83	gold quality
intestine	UBERON:0000160	61.67	gold quality
fundus of stomach	UBERON:0001160	61.27	gold quality
lymph node	UBERON:0000029	60.88	gold quality
heart	UBERON:0000948	60.76	gold quality
right coronary artery	UBERON:0001625	60.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	60.60	gold quality
transverse colon	UBERON:0001157	60.57	gold quality
body of stomach	UBERON:0001161	60.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, HR, MYOD1, MYOG

Literature-anchored findings (GeneRIF, showing 40)

• analysis of regulation of MuSK expression by a novel signaling pathway (PMID:12885777)
• Missense mutation does not affect MuSK catalytic kinase activity but diminishes expression and stability. (PMID:15496425)
• Thus, an agrin/MuSK complex may form part of a motor neuron stop signal involved in “reverse signaling” to the motor neuron. (PMID:15691710)
• A low-molecular weight isoform of muscle-specific receptor tyrosine kinase in human sperm localized in the flagellar mid-piece region. (PMID:16487930)
• Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK (PMID:16794080)
• Altogether, these results indicate that anti-MuSK Abs could be pathogenic by contributing to the muscle atrophy in MuSK+ MG patients. (PMID:16857268)
• muscle-specific receptor tyrosine kinase activation and binding to dystroglycan are regulated by alternative mRNA splicing of agrin (PMID:17012237)
• Testing of human myotubes for the presence and activation of MuSK by exposing them to laminin. (PMID:17192614)
• We describe a case of epileptic seizures secondary to myasthenia gravis caused by autoantibodies to the MUSK receptor. These autoantibodies affected the brain as well. (PMID:17661994)
• the COOH-terminal NES and Src homology 2 target motifs play key roles in Dok-7/MuSK signaling for neuromuscular synaptogenesis. (PMID:18165682)
• We describe a transient neonatal myasthenic syndrome with anti-musk antibodies. (PMID:18378885)
• IgG from anti-MuSK-positive patients can cause myasthenia gravis when injected into mice. (PMID:18384168)
• single-fiber electromyography of distal limb muscles tends to have a lower yield of abnormality in MuSK-antibody-positive patients than either acetylcholine receptor-antibody-positive or seronegative myasthenia gravis (PMID:18567855)
• Thymectomy is mostly considered scarcely effective; however, at present, no firm conclusions can be drawn on its role in the treatment of this form of myasthenia gravis (PMID:18567856)
• Anti-MuSK protein positive patients have more predominantly bulbar involvement and had more severe myasthenia gravis. (PMID:19327804)
• Anti-MuSK antibodies influence the activity of MuSK molecules without reducing their number, thereby diminishing the size of the endplate and affecting the functioning of acetylcholine receptors. (PMID:19745065)
• This study report a family known so far with a congenital myasthenic syndromes due to a mutation in the MUSK gene. (PMID:19949040)
• these findings demonstrate that missense mutations in MUSK can result in a severe form of congenital myasthenic syndrome and indicate that the inability of MuSK mutants to interact with Dok-7. (PMID:20371544)
• The importance of MuSK as a synapse organiser is highlighted by cases of autoimmune myasthenia gravis in which MuSK autoantibodies can deplete MuSK from the postsynaptic membrane, leading to complete disassembly of the adult neuromuscular junction. (PMID:20974278)
• Two family cases are reported that transmit MuSK antibody myasthenia gravis to the offspring by different maternal mechanisms. (PMID:21386774)
• Lrp4 is a cis-acting ligand for MuSK (PMID:21969364)
• The ability of immobilized MuSK extracellular domain to remove practically all anti-MuSK antibodies from patients’ sera should prove invaluable for development of an antigen-specific therapeutic approach for MuSK myasthenia gravis. (PMID:21993075)
• MuSK kinase activity is necessary for substrate-dependent acetylcholine receptor cluster formation (PMID:22210232)
• We report a novel mutation in MUSK leading to a Congenital myasthenic syndromes (PMID:23326516)
• MUSK is associated with a small but variable subgroup of distinct phenotypes in Thai patients with myasthenia gravis who have MUSK autoantibodies. (PMID:23352351)
• MuSK is activated in a complex spatio-temporal manner to cluster acetylcholine receptors on the postsynaptic (muscle) side of the synapse and to induce differentiation of the nerve terminal on the presynaptic side. (Review) (PMID:23467009)
• We proved that the missense mutations in ColQ-CTD cause endplate AChE deficiency by compromising ColQ-MuSK interaction at the NMJ. (PMID:23553736)
• MUSK antibodies may induce phenotypically disruptive actions at the neuromuscular junction by binding acetylcholinesterase (AChE) via its collagen tail, producing a reduction in synaptic AChE activity. (PMID:23720161)
• This study provides a replication of the highly significant associations of both HLA-DRB1( *)16,-DRB1( *)14 and -DQB1( *)05 with MuSK-MG. (PMID:23993985)
• Identification of a novel missense mutation c.114T > A; p.Asp38Glu heteroallelic to a genomic deletion encompassing exons 2-3 of MUSK that explain a limb-girdle congenital myasthenic syndrome in two affected brothers of a Turkish family. (PMID:24183479)
• MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters (PMID:24244707)
• pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation. (PMID:24297891)
• HEp-2 M4 cells revealed a high specificity for the detection of MuSK autoantibodies from 25 patient sera. (PMID:24416182)
• [review] Recent discovery of two novel target proteins (MuSK and LRP4) has reduced the percentage of patients without known autoantibodies, although there are still some seronegative myasthenia gravis patients. (PMID:24530233)
• HnRNP C, YB-1 and hnRNP L coordinately enhance skipping of human MUSK exon 10 to generate a Wnt-insensitive MuSK isoform. (PMID:25354590)
• A Dutch founder mutation in MUSK causing fetal akinesia deformation sequence has been found in 14 fetuses. (PMID:25537362)
• To our knowledge, this is the first report showing that a mutation in MuSK is associated with Fetal akinesia deformation sequence syndrome (PMID:25612909)
• Immunosuppression attenuates the Th1 response in AChR-myasthenia gravis (MG) and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially. (PMID:25893403)
• Classical electromyography revealed the presence of myopathic changes more frequently in MuSK myasthenia gravis compared to acetylcholine receptor myasthenia gravis (PMID:26778359)
• Gene expression profiling showed that MuSK was required for the BMP4-induced expression of a subset of genes in myoblasts, including regulator of G protein signaling 4 (Rgs4). (PMID:27601729)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Musk	ENSMUSG00000057280
rattus_norvegicus	Musk	ENSRNOG00000033567
drosophila_melanogaster	Nrk	FBGN0020391

Paralogs (53): INSRR (ENSG00000027644), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Muscle, skeletal receptor tyrosine-protein kinase — O15146 (reviewed: O15146)

Alternative names: Muscle-specific tyrosine-protein kinase receptor

All UniProt accessions (3): A0A087WSY1, O15146, F6XAJ2

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role in acetylcholinesterase (AChE) localization at the neuromuscular junctions (NMJ) via its interaction wit COLQ. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation.

Subunit / interactions. Monomer. Homodimer. Interacts with LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK. Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via cytoplasmic part) with DOK7 (via IRS-type PTB domain); requires MUSK phosphorylation. Interacts with DVL1 (via DEP domain); the interaction is direct and mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering. Interacts with PDZRN3; this interaction is enhanced by agrin. Interacts with FNTA; the interaction is direct and mediates AGRIN-induced phosphorylation and activation of FNTA. Interacts with CSNK2B; mediates regulation by CK2. Interacts (via the cytoplasmic domain) with DNAJA3. Interacts with NSF; may regulate MUSK endocytosis and activity. Interacts with CAV3; may regulate MUSK signaling. Interacts with RNF31. Interacts with DOK7. Interacts with the acetylcholinesterase collagenic tail peptide (COLQ); the interaction may play a role in acetylcholinesterase (AChE) localization at the neuromuscular junctions (NMJ).

Subcellular location. Postsynaptic cell membrane.

Post-translational modifications. Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation. Phosphorylated. Phosphorylation is induced by AGRIN in a LRP4-dependent manner. Autophosphorylated. Autophosphorylation at Tyr-554 is required for interaction with DOK7 which in turn stimulates the phosphorylation and the activation of MUSK. Neddylated.

Disease relevance. Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9) [MIM:616325] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS9 is a disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. The disease is caused by variants affecting the gene represented in this entry. MUSK mutations lead to decreased agrin-dependent AChR aggregation, a critical step in the formation of the neuromuscular junction. Fetal akinesia deformation sequence 1 (FADS1) [MIM:208150] A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS1 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Positively regulated by CK2.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
O15146-1	1	yes
O15146-2	2
O15146-3	3

RefSeq proteins (3): NP_001159752, NP_001159753, NP_005583* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020067	Frizzled_dom	Domain
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036790	Frizzled_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF01392, PF07679, PF07714, PF13927

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (55 total): sequence variant 21, disulfide bond 9, domain 5, modified residue 4, splice variant 3, mutagenesis site 3, binding site 2, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9NWG	X-RAY DIFFRACTION	1.7
9LGG	X-RAY DIFFRACTION	2.69
9NWH	X-RAY DIFFRACTION	2.8
8S9P	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15146-F1	76.57	0.37

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): 725 (proton acceptor)

Ligand- & substrate-binding residues (2): 581–589; 609

Post-translational modifications (4): 554, 681, 698, 755

Disulfide bonds (9): 49–99, 98–112, 142–190, 233–282, 317–382, 325–375, 366–406, 394–447, 398–434

Glycosylation sites (2): 222, 338

Mutagenesis-validated functional residues (3):

Position	Phenotype
584	mild decrease in kinase activity.
609	severe loss of kinase activity.
743	severe loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3000178	ECM proteoglycans
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 402 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MORF_RAGE, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GCANCTGNY_MYOD_Q6, MODULE_64, GOBP_GROWTH, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5

GO Biological Process (11): positive regulation of protein phosphorylation (GO:0001934), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), neuromuscular junction development (GO:0007528), memory (GO:0007613), regulation of synaptic assembly at neuromuscular junction (GO:0008582), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), skeletal muscle acetylcholine-gated channel clustering (GO:0071340), positive regulation of protein geranylgeranylation (GO:2000541), protein phosphorylation (GO:0006468), positive regulation of macromolecule metabolic process (GO:0010604)

GO Molecular Function (10): protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), Wnt-protein binding (GO:0017147), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): plasma membrane (GO:0005886), neuromuscular junction (GO:0031594), signaling receptor complex (GO:0043235), postsynaptic membrane (GO:0045211), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of protein modification process	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of phosphorylation	1
enzyme-linked receptor protein signaling pathway	1
synapse organization	1
learning or memory	1
regulation of developmental growth	1
synaptic assembly at neuromuscular junction	1
regulation of synapse assembly	1
regulation of neuromuscular junction development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular developmental process	1
postsynaptic membrane organization	1
neuromuscular junction development	1
receptor clustering	1
protein geranylgeranylation	1
regulation of protein geranylgeranylation	1
phosphorylation	1
protein modification process	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of macromolecule metabolic process	1
protein kinase activity	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein 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

Protein interactions and networks

STRING

1704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUSK	AGRN	O00468	999
MUSK	DOK7	Q18PE1	994
MUSK	LRP4	O75096	994
MUSK	RAPSN	Q13702	990
MUSK	COLQ	Q9Y215	985
MUSK	DVL1	O14640	904
MUSK	ACHE	P22303	860
MUSK	CHRNE	Q04844	842
MUSK	SYNE1	Q8NF91	819
MUSK	UTRN	P46939	812
MUSK	CHRNB1	P11230	793
MUSK	CHRNG	P07510	776
MUSK	CHRND	Q07001	759
MUSK	DAG1	Q14118	749
MUSK	BCHE	P06276	743

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CDC37	MUSK	psi-mi:“MI:0915”(physical association)	0.600
HSP90AB1	MUSK	psi-mi:“MI:0915”(physical association)	0.520
YWHAE	MUSK	psi-mi:“MI:0915”(physical association)	0.400
SFN	MUSK	psi-mi:“MI:0915”(physical association)	0.400
IL6	MUSK	psi-mi:“MI:0915”(physical association)	0.400
MUSK	FKBP5	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	MUSK	psi-mi:“MI:0915”(physical association)	0.400
MUSK	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.400
ILKAP	MUSK	psi-mi:“MI:0915”(physical association)	0.370
STYX	MUSK	psi-mi:“MI:0915”(physical association)	0.370
MUSK	HLA-B	psi-mi:“MI:0914”(association)	0.350
MUSK	DNAJC13	psi-mi:“MI:0914”(association)	0.350
Chrnb1	MUSK	psi-mi:“MI:0403”(colocalization)	0.350
MUSK	ARHGAP32	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (88): ADAM30 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), RBSN (Affinity Capture-MS), ILKAP (Two-hybrid), STYX (Two-hybrid), ERBB2IP (Affinity Capture-Western), MUSK (Affinity Capture-Western), MUSK (Reconstituted Complex), ERBB2IP (Two-hybrid), MUSK (Affinity Capture-Western), MUSK (Affinity Capture-Western), SYNE1 (Two-hybrid), MUSK (Affinity Capture-Western), RBSN (Affinity Capture-MS), ADAM30 (Affinity Capture-MS)

ESM2 similar proteins: B3MH43, B3MKS0, B3N666, B3NS99, B4GBH0, B4GKZ8, B4HNW4, B4HY03, B4JEF2, B4KJW1, B4KPU0, B4LRN7, B4MR28, B4N072, B4NZY8, B4P5Q9, B4Q599, B4QC63, G5EBF1, G5EGK5, O15146, O42127, P11362, P16092, P21804, P22182, P83097, Q02858, Q03364, Q04589, Q07407, Q08180, Q09147, Q27324, Q290N5, Q29JX6, Q4H3K6, Q6AWJ9, Q8AXC6, Q8JFR5

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A2A8L5, A2AJ76, A4IFW2, A4IGL7, A4IIW9, A5JUY8, A7MBJ4, A8WGA3, A8WQH2, B0BNK7, B3A0P3, D2HFT7, D3YXG0, D4A1J9, D4ABX8, G5EBF1, G5EG78, H2A0M7, O15146, O35158, O55005, O89026, P05164, P07202, P09933, P0C6S8, P0C7J6, P11247, P11678, P14650, P16621, P22079, P23468, P35419, P49290, P70193, P80025

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
DOK7	up-regulates	MUSK	binding
WNT11	up-regulates	MUSK	binding
WNT9A	up-regulates	MUSK	binding
MUSK	up-regulates	WNT11	binding
LRP4	“up-regulates activity”	MUSK	binding
MUSK	“up-regulates activity”	MUSK	phosphorylation
MUSK	“up-regulates activity”	DOK7	phosphorylation
PDZRN3	“down-regulates quantity”	MUSK	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	44
Likely pathogenic	34
Uncertain significance	313
Likely benign	372
Benign	64

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068787	NM_005592.4(MUSK):c.581dup (p.Asn194fs)	Pathogenic
1452397	NM_005592.4(MUSK):c.2170C>T (p.Arg724Ter)	Pathogenic
1458702	NM_005592.4(MUSK):c.582del (p.Asn194fs)	Pathogenic
1460076	NC_000009.11:g.(?113449377)(113457830_?)del	Pathogenic
1460264	NC_000009.11:g.(?113431185)(113550138_?)del	Pathogenic
190466	NM_005592.4(MUSK):c.40dup (p.Thr14fs)	Pathogenic
2018617	NM_005592.4(MUSK):c.31_34del (p.His11fs)	Pathogenic
2025875	NM_005592.4(MUSK):c.1466C>G (p.Ser489Ter)	Pathogenic
2080073	NM_005592.4(MUSK):c.1555C>T (p.Arg519Ter)	Pathogenic
211542	NM_005592.4(MUSK):c.79+2T>G	Pathogenic
2139033	NM_005592.4(MUSK):c.2358G>A (p.Trp786Ter)	Pathogenic
2425378	NC_000009.11:g.(?113444934)(113449568_?)del	Pathogenic
2425379	NC_000009.11:g.(?113509901)(113538955_?)del	Pathogenic
2928495	NM_005592.4(MUSK):c.1218C>A (p.Cys406Ter)	Pathogenic
2930356	NM_005592.4(MUSK):c.845_848dup (p.Ile283fs)	Pathogenic
2931650	NM_005592.4(MUSK):c.2010del (p.Met670fs)	Pathogenic
2932520	NM_005592.4(MUSK):c.461G>A (p.Trp154Ter)	Pathogenic
2936081	NM_005592.4(MUSK):c.2T>C (p.Met1Thr)	Pathogenic
2937395	NM_005592.4(MUSK):c.545dup (p.Glu183fs)	Pathogenic
2941162	NM_005592.4(MUSK):c.1840del (p.Glu614fs)	Pathogenic
2941926	NM_005592.4(MUSK):c.1826del (p.Lys609fs)	Pathogenic
2944470	NM_005592.4(MUSK):c.2021_2022dup (p.Val675fs)	Pathogenic
2945921	NM_005592.4(MUSK):c.868del (p.Glu290fs)	Pathogenic
2948129	NM_005592.4(MUSK):c.166dup (p.Gln56fs)	Pathogenic
2948197	NM_005592.4(MUSK):c.1299_1300del (p.Cys434fs)	Pathogenic
2949414	NM_005592.4(MUSK):c.1384del (p.Thr462fs)	Pathogenic
2951981	NM_005592.4(MUSK):c.790C>T (p.Arg264Ter)	Pathogenic
2953074	NM_005592.4(MUSK):c.2122C>T (p.Gln708Ter)	Pathogenic
2953184	NM_005592.4(MUSK):c.1592C>G (p.Ser531Ter)	Pathogenic
2953223	NM_005592.4(MUSK):c.2192del (p.Cys731fs)	Pathogenic

SpliceAI

2609 predictions. Top by Δscore:

Variant	Effect	Δscore
9:110682669:TTCA:T	acceptor_loss	1.0000
9:110682670:TCAGC:T	acceptor_loss	1.0000
9:110682672:A:AC	acceptor_loss	1.0000
9:110682672:A:AG	acceptor_gain	1.0000
9:110682673:G:GT	acceptor_gain	1.0000
9:110682673:GC:G	acceptor_gain	1.0000
9:110682673:GCTC:G	acceptor_gain	1.0000
9:110682673:GCTCC:G	acceptor_gain	1.0000
9:110682796:ATTAA:A	donor_gain	1.0000
9:110682797:TTAA:T	donor_gain	1.0000
9:110682798:TAA:T	donor_gain	1.0000
9:110682799:AA:A	donor_gain	1.0000
9:110682800:AGT:A	donor_loss	1.0000
9:110682801:G:GG	donor_gain	1.0000
9:110685053:A:T	donor_gain	1.0000
9:110687107:T:TA	acceptor_gain	1.0000
9:110687113:GCAG:G	acceptor_loss	1.0000
9:110687115:A:AG	acceptor_gain	1.0000
9:110687116:G:GG	acceptor_gain	1.0000
9:110687116:GA:G	acceptor_gain	1.0000
9:110687116:GACT:G	acceptor_gain	1.0000
9:110687116:GACTC:G	acceptor_gain	1.0000
9:110687264:GATGA:G	donor_gain	1.0000
9:110687265:A:G	donor_gain	1.0000
9:110687267:GA:G	donor_gain	1.0000
9:110687269:G:GG	donor_gain	1.0000
9:110695397:TTTTA:T	acceptor_loss	1.0000
9:110695398:TTTA:T	acceptor_loss	1.0000
9:110695399:TTAG:T	acceptor_loss	1.0000
9:110695400:TA:T	acceptor_loss	1.0000

AlphaMissense

5707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:110734355:T:A	W245R	1.000
9:110734355:T:C	W245R	1.000
9:110734357:G:C	W245C	1.000
9:110734357:G:T	W245C	1.000
9:110682734:T:C	F47S	0.999
9:110682775:T:A	W61R	0.999
9:110682775:T:C	W61R	0.999
9:110682776:G:C	W61S	0.999
9:110682777:G:C	W61C	0.999
9:110682777:G:T	W61C	0.999
9:110687161:T:C	L84P	0.999
9:110695504:T:A	W154R	0.999
9:110695504:T:C	W154R	0.999
9:110695506:G:C	W154C	0.999
9:110695506:G:T	W154C	0.999
9:110734314:T:C	L231P	0.999
9:110734319:T:C	C233R	0.999
9:110734356:G:C	W245S	0.999
9:110747696:T:C	L270P	0.999
9:110747725:T:G	Y280D	0.999
9:110747731:T:C	C282R	0.999
9:110747733:C:G	C282W	0.999
9:110800606:A:T	D743V	0.999
9:110697400:T:G	Y188D	0.998
9:110734321:T:G	C233W	0.998
9:110747738:C:A	A284D	0.998
9:110800552:A:T	D725V	0.998
9:110800744:G:A	G789D	0.998
9:110800753:T:C	L792P	0.998
9:110800755:T:A	W793R	0.998

dbSNP variants (sampled 300 via entrez): RS1000000530 (9:110699645 C>T), RS1000074259 (9:110775675 T>C), RS1000080653 (9:110784671 C>A), RS1000104614 (9:110791043 G>A,T), RS1000136888 (9:110730608 T>C,G), RS1000164286 (9:110763546 A>T), RS1000170541 (9:110805754 T>C), RS1000187486 (9:110683443 G>A,T), RS1000190299 (9:110676570 G>A,T), RS1000190412 (9:110773924 G>A), RS1000200829 (9:110721145 G>A,C,T), RS1000212679 (9:110712932 A>G,T), RS1000221573 (9:110806144 T>A,C), RS1000247570 (9:110724639 C>A), RS1000268054 (9:110755090 A>G)

Disease associations

OMIM: gene MIM:601296 | disease phenotypes: MIM:616325, MIM:208150, MIM:608931

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 9	Strong	Autosomal recessive
fetal akinesia deformation sequence 1	Strong	Autosomal recessive
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive

Mondo (4): congenital myasthenic syndrome 9 (MONDO:0014587), fetal akinesia deformation sequence 1 (MONDO:0100101), congenital myasthenic syndrome 4C (MONDO:0012157), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (2): Congenital myasthenic syndrome (Orphanet:590), Fetal akinesia deformation sequence (Orphanet:994)

HPO phenotypes

136 total (30 of 136 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000437	Depressed nasal tip
HP:0000467	Neck muscle weakness
HP:0000470	Short neck
HP:0000476	Cystic hygroma
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000581	Blepharophimosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000651	Diplopia
HP:0000689	Dental malocclusion
HP:0000883	Thin ribs
HP:0000961	Cyanosis
HP:0001059	Pterygium

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001444_7	Pulmonary function decline	7.000000e-07
GCST001843_3	Type 2 diabetes (dietary heme iron intake interaction)	1.000000e-06
GCST006979_171	Heel bone mineral density	1.000000e-10
GCST006979_172	Heel bone mineral density	4.000000e-13
GCST008158_112	Body mass index	3.000000e-06
GCST008462_5	Plasma factor V levels in venous thrombosis (conditioned on rs6027)	2.000000e-06
GCST009391_1000	Metabolite levels	4.000000e-06
GCST009391_812	Metabolite levels	1.000000e-06
GCST012367_2	Orofacial cleft x maternal periconceptional smoking interaction (1df)	2.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0008355	dietary heme iron intake measurement
EFO:0009270	heel bone mineral density
EFO:0004340	body mass index
EFO:0010540	thiamine measurement
EFO:0010397	sphingomyelin 24:0 measurement
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5684 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 215,713 (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
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL475251	R-406	2	762
CHEMBL5077961	MILREBRUTINIB	2	24
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL575448	BMS-754807	2	406
CHEMBL1908397	KW-2449	1	622
CHEMBL4212531	PF-06273340	1	55
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type IX RTKs: MuSK

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

Ligand	Action	Affinity	Parameter
compound 1d [PMID: 21493067]	Inhibition	6.65	pIC50
compound 25 [PMID: 17935989]	Inhibition	5.78	pKi

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 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
Staurosporine	KD	1.7 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 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
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 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
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

53 potent at pChembl≥5 of 53 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.51	Kd	3.1	nM	AST-487
8.42	IC50	3.8	nM	STAUROSPORINE
8.04	IC50	9.1	nM	CRIZOTINIB
8.00	Kd	10	nM	LINIFANIB
7.89	IC50	12.83	nM	CHEMBL5423601
7.89	Kd	13	nM	FORETINIB
7.28	IC50	53	nM	PF-06273340
7.26	IC50	54.4	nM	STAUROSPORINE
7.07	Kd	86	nM	STAUROSPORINE
7.00	Kd	100	nM	SU-014813
7.00	Kd	100	nM	R-406
6.96	Kd	110	nM	CHEMBL4792981
6.89	Kd	130	nM	SORAFENIB
6.80	IC50	158	nM	STAUROSPORINE
6.70	Kd	200	nM	KW-2449
6.65	IC50	224	nM	CHEMBL1774056
6.64	Kd	230	nM	CRIZOTINIB
6.59	IC50	257	nM	CHEMBL5559304
6.58	Kd	260	nM	TAE-684
6.54	IC50	290	nM	STAUROSPORINE
6.52	Kd	300	nM	TOZASERTIB
6.51	IC50	306	nM	MILREBRUTINIB
6.41	Kd	390	nM	QUIZARTINIB
6.31	Kd	490	nM	SUNITINIB
6.28	Kd	530	nM	CHEMBL4553037
6.23	Kd	590	nM	NINTEDANIB
6.16	IC50	690	nM	CHEMBL3422092
6.10	Kd	800	nM	FEDRATINIB
6.08	Kd	830	nM	DOVITINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Kd	1000	nM	QUIZARTINIB
5.82	Kd	1500	nM	DEFOSBARASERTIB
5.72	Kd	1900	nM	DORAMAPIMOD
5.39	Kd	4100	nM	LESTAURTINIB
5.25	Kd	5600	nM	CHEMBL1908395
5.22	Kd	6000	nM	BMS-754807

PubChem BioAssay actives

49 with measured affinity, of 706 total; 31 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
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435678: Binding constant for MUSK kinase domain	kd	0.0031	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	1308970: Inhibition of MUSK (unknown origin) incubated for 1 hr by spectrophotometric analysis	ic50	0.0038	uM
Crizotinib	2161835: Inhibition of human N-terminal GST-fused MUSK catalytic domain (527 to 869(end) residues) expressed in baculovirus expression system using CSKtide as substrate measured after 5 hrs by off-chip mobility shift assay relative to control	ic50	0.0091	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	435678: Binding constant for MUSK kinase domain	kd	0.0100	uM
N-[3-cyclopropyl-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-5-methyl-18-oxo-9-oxa-17,23,25,26-tetrazatetracyclo[17.5.2.14,8.022,25]heptacosa-1(24),4,6,8(27),19(26),20,22-heptaen-2-yne-6-carboxamide	2014041: Inhibition of Musk (unknown origin)	ic50	0.0128	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	625022: Binding constant for MUSK kinase domain	kd	0.0130	uM
N-[5-[2-amino-7-(1-hydroxy-2-methylpropan-2-yl)pyrrolo[2,3-d]pyrimidine-5-carbonyl]-3-pyridinyl]-2-(5-chloro-2-pyridinyl)acetamide	1686419: Inhibition of MUSK (unknown origin)	ic50	0.0530	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435678: Binding constant for MUSK kinase domain	kd	0.1000	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	625022: Binding constant for MUSK kinase domain	kd	0.1000	uM
N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-3-(3-propan-2-yloxy-1H-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine	692574: Inhibition of MuSk	ic50	0.1000	uM
N-[(1R)-1-(3,5-difluorophenyl)ethyl]-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-amine	1741257: Binding affinity to wild-type human partial length MUSK (M553 to V869 residues) expressed in bacterial expression system by Kinomescan method relative to control	kd	0.1100	uM
Sorafenib	435678: Binding constant for MUSK kinase domain	kd	0.1300	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625022: Binding constant for MUSK kinase domain	kd	0.2000	uM
5-fluoro-2-[[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]amino]-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyridine-3-carbonitrile	596575: Inhibition of human MuSk	ic50	0.2240	uM
N-[(2S)-1-(azetidin-1-yl)propan-2-yl]-3-[2-(3,5-dimethoxyanilino)pyrimidin-4-yl]-1-methylpyrazole-5-carboxamide	2075969: Inhibition of MUSK (unknown origin)	ic50	0.2570	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	625022: Binding constant for MUSK kinase domain	kd	0.2600	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435678: Binding constant for MUSK kinase domain	kd	0.3000	uM
2-[3-[2-amino-6-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one	1830226: Inhibition of human MUSK expressed in baculovirus expression system by mobility shift assay	ic50	0.3060	uM
Sunitinib	435678: Binding constant for MUSK kinase domain	kd	0.4900	uM
(4R)-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide	1625889: Binding affinity to wild type human partial length MUSK (553 to 869 residues) expressed in bacterial expression system preincubated for 1 hr measured after 30 mins by qPCR method	kd	0.5300	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625022: Binding constant for MUSK kinase domain	kd	0.5900	uM
N-[(R)-cyclopropyl(pyridin-2-yl)methyl]-3-[4-[(1S,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]phenyl]-1H-indazole-5-carboxamide	1203315: Inhibition of human MuSK by millipore radiometric assay	ic50	0.6900	uM
Fedratinib	625022: Binding constant for MUSK kinase domain	kd	0.8000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435678: Binding constant for MUSK kinase domain	kd	0.8300	uM
Quizartinib	507636: Binding affinity to MUSK	kd	1.0000	uM
Momelotinib	2183911: Inhibition of MUSK (unknown origin)	ic50	1.0000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	435678: Binding constant for MUSK kinase domain	kd	1.5000	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	435678: Binding constant for MUSK kinase domain	kd	1.9000	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	625022: Binding constant for MUSK kinase domain	kd	4.1000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625022: Binding constant for MUSK kinase domain	kd	5.6000	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	2167422: Binding affinity to MUSK (unknown origin) by phage based competition assay	kd	6.0000	uM

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
Zoledronic Acid	decreases expression	1
Asbestos	affects expression	1
Sarin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1

ChEMBL screening assays

247 unique, capped per target: 247 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1035907	Binding	Binding affinity to human MUSK at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2CY	HAP1 MUSK (-) 1	Cancer cell line	Male
CVCL_E2CZ	HAP1 MUSK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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