1. Gene Aliases

Myot, Myotilin, TTID, Titin Immunoglobulin Domain Protein (Myotilin), Myofibrillar Titin-Like Ig Domains Protein, 57 KDa Cytoskeletal Protein, LGMD1A, LGMD1, Limb-Girdle Muscular Dystrophy 1A (Autosomal Dominant), Titin Immunoglobulin Domain Protein, MFM3, TTOD

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=MYOT&keywords=myot].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

axon guidance [The chemotaxis process that directs the migration of an axon growth cone to a specific target site in response to a combination of attractive and repulsive cues. GO:0007411]

biological_process [A biological process is the execution of a genetically-encoded biological module or program. It consists of all the steps required to achieve the specific biological objective of the module. A biological process is accomplished by a particular set of molecular functions carried out by specific gene products (or macromolecular complexes), often in a highly regulated manner and in a particular temporal sequence.|Note that, in addition to forming the root of the biological process ontology, this term is recommended for use for the annotation of gene products whose biological process is unknown. When this term is used for annotation, it indicates that no information was available about the biological process of the gene product annotated as of the date the annotation was made; the evidence code 'no data' (ND), is used to indicate this. GO:0008150]

dendrite self-avoidance [The process in which dendrites recognize and avoid contact with sister dendrites from the same cell. GO:0070593]

homophilic cell adhesion via plasma membrane adhesion molecules [The attachment of a plasma membrane adhesion molecule in one cell to an identical molecule in an adjacent cell. GO:0007156]

MSigDB Signatures:

CHEMELLO_SOLEUS_VS_EDL_MYOFIBERS_UP: Genes up-regulated in type 1 (soleus) vs type 2B (EDL) myofibers.[https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHEMELLO_SOLEUS_VS_EDL_MYOFIBERS_UP.html]

CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP: Up-regulated genesin the left ventricle myocardium of patients with heart failure following implantation of LVAD (left ventricular assist device).[https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a cystoskeletal protein which plays a significant role in the stability of thin filaments during muscle contraction. This protein binds F-actin, crosslinks actin filaments, and prevents latrunculin A-induced filament disassembly. Mutations in this gene have been associated with limb-girdle muscular dystrophy and myofibrillar myopathies. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[provided by RefSeq, Oct 2008]

GeneCards Summary: MYOT (Myotilin) is a Protein Coding gene. Diseases associated with MYOT include Myopathy, Myofibrillar, 3 and Myofibrillar Myopathy. Gene Ontology (GO) annotations related to this gene include actin binding and alpha-actinin binding. An important paralog of this gene is MYPN.

UniProtKB/Swiss-Prot Summary: Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells.

8. Cellular Location of Gene Product

Selective cytoplasmic expression in skeletal muscle. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000120729/subcellular]

9. Mechanistic Information

Summary

Myotilin, encoded by the MYOT gene, is integral in maintaining the structural integrity of muscle cells, specifically through its role in stabilizing thin filaments during muscle contraction [CS: 9]. This stabilization is achieved by its ability to bind F-actin and crosslink actin filaments, crucial for proper muscle function [CS: 9]. In the context of heart diseases, MYOT dysregulation can significantly impact cardiac muscle function [CS: 7].

For instance, in dilated cardiomyopathy (DCM), an increased expression of MYOT (along with its interactors PDLIM5, LDB3, and MYOZ2) was observed [CS: 6]. This upregulation suggests a compensatory mechanism where increased MYOT expression might aim to reinforce the structural integrity of cardiac muscle cells [CS: 6]. This reinforcement is essential in counteracting the weakening and enlargement of the heart muscle characteristic of DCM [CS: 6]. Similarly, the association of MYOT with heart rate and atrial fibrillation indicates its role in maintaining regular cardiac muscle function [CS: 5]. Dysregulation here might lead to abnormal heart rhythms due to compromised muscle fiber stability [CS: 5].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: skeletal muscle, tongue (group enriched) [https://www.proteinatlas.org/ENSG00000120729/tissue]

Cell type enchanced: skeletal myocytes (cell type enriched) [https://www.proteinatlas.org/ENSG00000120729/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest