MUSK

Protein identityUniProt · HPA

UniProt accession

O15146

Gene

MUSK

Ensembl

ENSG00000030304

Chromosome

9

Canonical length

869 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Quaternary structure

Homodimer

OverviewNCBI Gene

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.[provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

869 residues, UniProt reviewed canonical sequence.

>O15146|MUSK
     1  MRELVNIPLV HILTLVAFSG TEKLPKAPVI TTPLETVDAL VEEVATFMCA VESYPQPEIS
    61  WTRNKILIKL FDTRYSIREN GQLLTILSVE DSDDGIYCCT ANNGVGGAVE SCGALQVKMK
   121  PKITRPPINV KIIEGLKAVL PCTTMGNPKP SVSWIKGDSP LRENSRIAVL ESGSLRIHNV
   181  QKEDAGQYRC VAKNSLGTAY SKVVKLEVEV FARILRAPES HNVTFGSFVT LHCTATGIPV
   241  PTITWIENGN AVSSGSIQES VKDRVIDSRL QLFITKPGLY TCIATNKHGE KFSTAKAAAT
   301  ISIAEWSKPQ KDNKGYCAQY RGEVCNAVLA KDALVFLNTS YADPEEAQEL LVHTAWNELK
   361  VVSPVCRPAA EALLCNHIFQ ECSPGVVPTP IPICREYCLA VKELFCAKEW LVMEEKTHRG
   421  LYRSEMHLLS VPECSKLPSM HWDPTACARL PHLDYNKENL KTFPPMTSSK PSVDIPNLPS
   481  SSSSSFSVSP TYSMTVIISI MSSFAIFVLL TITTLYCCRR RKQWKNKKRE SAAVTLTTLP
   541  SELLLDRLHP NPMYQRMPLL LNPKLLSLEY PRNNIEYVRD IGEGAFGRVF QARAPGLLPY
   601  EPFTMVAVKM LKEEASADMQ ADFQREAALM AEFDNPNIVK LLGVCAVGKP MCLLFEYMAY
   661  GDLNEFLRSM SPHTVCSLSH SDLSMRAQVS SPGPPPLSCA EQLCIARQVA AGMAYLSERK
   721  FVHRDLATRN CLVGENMVVK IADFGLSRNI YSADYYKANE NDAIPIRWMP PESIFYNRYT
   781  TESDVWAYGV VLWEIFSYGL QPYYGMAHEE VIYYVRDGNI LSCPENCPVE LYNLMRLCWS
   841  KLPADRPSFT SIHRILERMC ERAEGTVSV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MUSK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

3.8 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MUSK.

Disease | AllUniProt

Conditions MUSK is implicated in, by any mechanism.

• Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (CMS9) MIM:616325
• Fetal akinesia deformation sequence 1 (FADS1) MIM:208150

Disease | GeneticClinVar

75 pathogenic / likely-pathogenic of 894 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital myasthenic syndrome 9
• Fetal akinesia deformation sequence 1
• Bilateral ptosis
• Respiratory insufficiency
• Stridor

Disease | AutoantibodyPubMed

Conditions in which antibodies against MUSK are reported. Each links to that disease's full target list.

• Myasthenia Gravis 256
• Muscle Weakness 23
• Thymoma 13
• Thymus Neoplasms 11
• COVID-19 5

Showing 5 of 16 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for MUSK from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.7

gnomAD pLI

0

gnomAD missense Z

1.09

DepMap mean gene effect

0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• cell surface receptor protein tyrosine kinase signaling pathway
• memory
• neuromuscular junction development
• positive regulation of gene expression
• positive regulation of protein phosphorylation
• regulation of synaptic assembly at neuromuscular junction
• skeletal muscle acetylcholine-gated channel clustering
• positive regulation of protein geranylgeranylation

Molecular functions

• ATP binding
• metal ion binding
• protein tyrosine kinase activity
• transmembrane receptor protein tyrosine kinase activity
• Wnt-protein binding

Cellular components

• neuromuscular junction
• plasma membrane
• postsynaptic membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Protein kinase, ATP binding site
• Frizzled domain
• Tyrosine-protein kinase, catalytic domain
• Immunoglobulin-like domain superfamily
• Frizzled cysteine-rich domain superfamily
• Receptor Tyrosine Kinase
• Fz domain
• Immunoglobulin I-set domain
• Protein tyrosine and serine/threonine kinase
• Immunoglobulin domain

KeywordsUniProt

• ATP-binding
• Cell membrane
• Congenital myasthenic syndrome
• Developmental protein
• Differentiation
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Kinase
• Magnesium
• Membrane
• Metal-binding
• Muscle protein
• Nucleotide-binding
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Repeat
• Signal
• Synapse
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of MUSK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CAV3
• CSNK2B
• DOK7
• DVL1
• FNTA
• LRP4
• NSF
• PDZRN3
• RNF31
• COLQ
• RINL
• DNAJA3
• CDC37