TISIDB

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell junction, synapse, postsynaptic cell membrane Single-pass type I membrane protein Note=Colocalizes with acetylcholine receptors (AChR) to the postsynaptic cell membrane of the neuromuscular junction.
Domain	PF01392 Fz domain PF07679 Immunoglobulin I-set domain PF07714 Protein tyrosine kinase
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 (PubMed:25537362). 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 within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001941 postsynaptic membrane organization GO:0007416 synapse assembly GO:0007528 neuromuscular junction development GO:0007611 learning or memory GO:0007613 memory GO:0008582 regulation of synaptic growth at neuromuscular junction GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0018342 protein prenylation GO:0018344 protein geranylgeranylation GO:0043113 receptor clustering GO:0044708 single-organism behavior GO:0046777 protein autophosphorylation GO:0048638 regulation of developmental growth GO:0050803 regulation of synapse structure or activity GO:0050807 regulation of synapse organization GO:0050808 synapse organization GO:0050890 cognition GO:0051124 synaptic growth at neuromuscular junction GO:0051668 localization within membrane GO:0051963 regulation of synapse assembly GO:0071340 skeletal muscle acetylcholine-gated channel clustering GO:0072657 protein localization to membrane GO:0097354 prenylation GO:1904396 regulation of neuromuscular junction development GO:2000539 regulation of protein geranylgeranylation GO:2000541 positive regulation of protein geranylgeranylation
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0019199 transmembrane receptor protein kinase activity
Cellular Component	GO:0031594 neuromuscular junction GO:0043235 receptor complex GO:0045211 postsynaptic membrane GO:0097060 synaptic membrane GO:0098794 postsynapse

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-3000178: ECM proteoglycans R-HSA-1474244: Extracellular matrix organization

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MUSK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of MUSK in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of MUSK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.152	0.707
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.629	0.653
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.454	0.801
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.519	0.0487
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.113	0.454
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	2.163	0.221
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.039	0.925
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.039	0.951
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.002	0.995

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MUSK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	8.2	-0.8	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	10.2	-2.8	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	11.8	2.5	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	18.2	-2.8	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MUSK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MUSK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MUSK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MUSK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MUSK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MUSK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MUSK
Name	muscle, skeletal, receptor tyrosine kinase
Aliases	CMS9; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor; Muscle, skeletal re ......
Chromosomal Location	9q31.3-q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MUSK collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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