MUSK

Chr 9q31.3

muscle associated receptor tyrosine kinase

MANE:: ENST00000374448.9

OMIM: 601296 ↗NCBI: 4593 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

MUSK · O15146

v62025-08-01

Predicted Aligned Error matrix for MUSK — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

76.4/ 100

Confident

869 residues

Confidence breakdown

Very high(≥ 90)37%
Confident(70–90)33%
Low(50–70)14%
Very low(< 50)16%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Arthrogryposis
BIALLELIC, autosomal or pseudoautosomal
Congenital myaesthenic syndrome
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Fetal hydrops
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Congenital myasthenic syndromes
0.79
fetal akinesia deformation sequence 1
0.74
congenital myasthenic syndrome 9
0.69
fetal akinesia deformation sequence
0.56
Postsynaptic congenital myasthenic syndromes
0.39
postsynaptic congenital myasthenic syndrome
0.38
Abnormality of limbs
0.35
Respiratory insufficiency
0.33
Delayed gross motor development
0.33
Stridor
0.33

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Muscle, skeletal receptor tyrosine-protein kinase

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 in acetylcholinesterase (AChE) localization at the neuromuscular junctions (NMJ) via its interaction wit COLQ (By similarity). May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity)