HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MYOT
myotilin
Chromosome 5 Β· 5q31.2
NCBI Gene: 9499Ensembl: ENSG00000120729.10HGNC: HGNC:12399UniProt: A0A0C4DFM5
53PubMed Papers
21Diseases
0Drugs
9Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
alpha-actinin bindingprotein bindingZ discplasma membranemyofibrillar myopathy 3Distal myotilinopathydistal myopathyFoot dorsiflexor weakness
✦AI Summary

MYOT encodes myotilin, a structural protein that serves as a component of actin cross-linking protein complexes involved in myofibril assembly and stability at the Z-lines in muscle cells 1. Myotilin functions as a Z-disc protein that maintains the structural integrity of muscle fibers through protein-protein interactions 2. Mutations in MYOT cause autosomal dominant myofibrillar myopathy (MFM), a hereditary neuromuscular disorder characterized by progressive muscle weakness that can manifest as distal myopathy affecting hands and feet, but may also involve proximal muscles and the heart 13. The disease typically presents in adulthood with slowly progressive weakness and is pathologically characterized by Z-disk alterations, myofibril disorganization, and abnormal protein aggregation 24. MYOT mutations result in the accumulation of degraded myofibrillar proteins forming large aggregates, though the exact mechanism by which mutated myotilin leads to protein aggregation remains unclear 25. Clinically, myotilinopathy represents part of the broader spectrum of myofibrillar myopathies caused by mutations in Z-disk-related proteins, contributing to the genetic heterogeneity of distal myopathies 67.

Sources cited
1
MYOT mutations cause autosomal dominant myopathy manifesting in adulthood with Z-disk alterations
PMID: 19181098
2
Myotilin is a Z-disk component involved in myofibril assembly and causes protein aggregation when mutated
PMID: 18769253
3
MYOT is associated with autosomal dominant distal myopathy
PMID: 33458580
4
Mutated myotilin causes structural and functional impairment in skeletal muscle
PMID: 37511242
5
MYOT encodes Z-line related proteins and causes myofibrillar myopathy
PMID: 24291893
6
Myotilinopathy is part of the clinical spectrum of genetic myopathies
PMID: 33250842
7
MYOT is one of seven genes causing myofibrillar myopathy with Z-line protein involvement
PMID: 22068470
Disease Associationsβ“˜21
myofibrillar myopathy 3Open Targets
0.79Strong
Distal myotilinopathyOpen Targets
0.72Strong
distal myopathyOpen Targets
0.35Weak
Distal amyotrophyOpen Targets
0.34Weak
Distal lower limb muscle weaknessOpen Targets
0.34Weak
EMG: myopathic abnormalitiesOpen Targets
0.34Weak
Fatty replacement of skeletal muscleOpen Targets
0.34Weak
Foot dorsiflexor weaknessOpen Targets
0.34Weak
Lower limb painOpen Targets
0.34Weak
Muscle fiber inclusion bodiesOpen Targets
0.34Weak
Urinary bladder sphincter dysfunctionOpen Targets
0.34Weak
myofibrillar myopathyOpen Targets
0.34Weak
hypothyroidismOpen Targets
0.27Weak
Progressive distal muscle weaknessOpen Targets
0.27Weak
Progressive proximal muscle weaknessOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
Autosomal dominant limb-girdle muscular dystrophyOpen Targets
0.19Weak
myofibrillar myopathy, dominantOpen Targets
0.19Weak
cardiomyopathyOpen Targets
0.12Weak
Myopathy, myofibrillar, 3UniProt
Pathogenic Variants9
NM_006790.3(MYOT):c.170C>T (p.Thr57Ile)Pathogenic
not provided|Myofibrillar myopathy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 57
NM_006790.3(MYOT):c.179C>T (p.Ser60Phe)Pathogenic
Myofibrillar myopathy 3|not provided|MYOT-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 60
NM_006790.3(MYOT):c.179C>G (p.Ser60Cys)Pathogenic
Myofibrillar myopathy 3|Myofibrillar myopathy|not provided|Distal myopathy
β˜…β˜…β˜†β˜†2026β†’ Residue 60
NM_006790.3(MYOT):c.164C>T (p.Ser55Phe)Pathogenic
Progressive distal muscle weakness;Progressive proximal muscle weakness|8 conditions|Myofibrillar myopathy 3|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 55
NM_006790.3(MYOT):c.116C>T (p.Ser39Phe)Pathogenic
not provided|Myofibrillar myopathy 3
β˜…β˜…β˜†β˜†2024β†’ Residue 39
NM_006790.3(MYOT):c.531+1G>ALikely pathogenic
Myofibrillar myopathy 3
β˜…β˜†β˜†β˜†2025
NM_006790.3(MYOT):c.1111C>T (p.Gln371Ter)Likely pathogenic
Myofibrillar myopathy 3
β˜…β˜†β˜†β˜†2025β†’ Residue 371
NM_006790.3(MYOT):c.634C>T (p.Gln212Ter)Likely pathogenic
Myofibrillar myopathy 3
β˜…β˜†β˜†β˜†2024β†’ Residue 212
NM_006790.3(MYOT):c.145_149del (p.Glu49fs)Likely pathogenic
Myofibrillar myopathy 3
β˜†β˜†β˜†β˜†β†’ Residue 49
View on ClinVar β†—
Related Genes
FLNCProtein interaction100%MYOZ1Protein interaction99%ACTN2Protein interaction95%MYOZ2Protein interaction93%BAG3Protein interaction90%ACTN3Protein interaction89%
Tissue Expression6 tissues
Heart
100%
Brain
43%
Ovary
5%
Liver
4%
Lung
4%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
MYOTFLNCMYOZ1ACTN2MYOZ2BAG3ACTN3
PROTEIN STRUCTURE
Preparing viewer…
PDB2KDG Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.92LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.67 [0.49–0.92]
RankingsWhere MYOT stands among ~20K protein-coding genes
  • #8,460of 20,598
    Most Researched53
  • #2,967of 5,498
    Most Pathogenic Variants9
  • #8,487of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedMYOT
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Panorama of the distal myopathies.
PMID: 33458580
Acta Myol Β· 2020
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent.
PMID: 33250842
Front Neurol Β· 2020
0.80
4
Human Mutated
PMID: 37511242
Int J Mol Sci Β· 2023
0.70
5
The Z-disk diseases.
PMID: 19181098
Adv Exp Med Biol Β· 2008
0.60