MYOT (myotilin)

Gene

• Entrez ID: 9499
• Gene name: Myotilin
• Gene symbol: MYOT
• Synonyms (NCBI Gene): LGMD1, LGMD1A, MFM3, TTID, TTOD
• Chromosome: 5
• Chromosome location: 5q31.2
• 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. Mutatio

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019225	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003779	Function	Actin binding	IEA
GO:0005515	Function	Protein binding	IPI	11038172, 12809483, 16076904, 25416956, 26871637, 32296183
GO:0005737	Component	Cytoplasm	IEA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0006936	Process	Muscle contraction	TAS	10958653
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IBA
GO:0007411	Process	Axon guidance	IEA
GO:0008046	Function	Axon guidance receptor activity	IBA
GO:0008307	Function	Structural constituent of muscle	TAS	10958653
GO:0015629	Component	Actin cytoskeleton	TAS	10369880
GO:0016020	Component	Membrane	IEA
GO:0030018	Component	Z disc	IDA	10958653
GO:0030018	Component	Z disc	IEA
GO:0030018	Component	Z disc	IMP	10958653
GO:0030424	Component	Axon	IBA
GO:0042383	Component	Sarcolemma	IEA
GO:0043025	Component	Neuronal cell body	IBA
GO:0050808	Process	Synapse organization	IBA
GO:0051393	Function	Alpha-actinin binding	IDA	10958653

Other IDs

• MIM: 604103
• HGNC: 12399
• e!Ensembl: ENSG00000120729

Protein

• UniProt ID: Q9UBF9
• Protein name: Myotilin (57 kDa cytoskeletal protein) (Myofibrillar titin-like Ig domains protein) (Titin immunoglobulin domain protein)
• Protein function: 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.
• PDB: 2KDG, 2KKQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07679	I-set	250 → 340	Immunoglobulin I-set domain	Domain
  PF07679	I-set	349 → 440	Immunoglobulin I-set domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in skeletal muscle (at protein level). Expressed in skeletal muscle, heart, bone marrow and thyroid gland. {ECO:0000269|PubMed:10369880, ECO:0000269|PubMed:10486214}.
• Sequence:

  MFNYERPKHFIQSQNPCGSRLQPPGPETSSFSSQTKQSSIIIQPRQCTEQRFSASSTLSS
  HITMSSSAFPASPKQHAGSNPGQRVTTTYNQSPASFLSSILPSQPDYNSSKIPSAMDSNY
  QQSSAGQPINAKPSQTANAKPIPRTPDHEIQGSKEALIQDLERKLKCKDTLLHNGNQRLT
  YEEKMARRLLGPQNAAAVFQAQDDSGAQDSQQHNSEHARLQVPTSQVRSRSTSRGDVNDQ
  DAIQEKFYPPRFIQVPENMSIDEGRFCRMDFKVSGLPAPDVSWYLNGRTVQSDDLHKMIV
  SEKGLHSLIFEVVRASDAGAYACVAKNRAGEATFTVQLDVLAKEHKRAPMFIYKPQSKKV
  LEGDSVKLECQISAIPPPKLFWKRNNEMVQFNTDRISLYQDNTGRVTLLIKDVNKKDAGW
  YTVSAVNEAGVTTCNTRLDVTARPNQTLPAPKQLRVRPTFSKYLALNGKGLNVKQAFNPE
  GEFQRLAAQSGLYESEEL

• Sequence length: 498

Pathways

KEGG:

Cytoskeleton in muscle cells

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Distal myopathy	Pathogenic	rs121908458	RCV005624677	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myofibrillar myopathy	Pathogenic	rs121908458	RCV000239643	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myofibrillar myopathy 3	Pathogenic; Likely pathogenic	rs28937597, rs121908457, rs121908458, rs121908460, rs121908461, rs1755403182	RCV000639976 RCV000794536 RCV000006193 RCV000006194 RCV000006195 RCV002512824 RCV003990367	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MYOT-related disorder	Likely pathogenic; Pathogenic	rs121908458	RCV003415664	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive distal muscle weakness	Likely pathogenic; Pathogenic	rs121908457	RCV000414759	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive proximal muscle weakness	Likely pathogenic; Pathogenic	rs121908457	RCV000414759	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathy	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISTAL AMYOTROPHY, ESPECIALLY OF THE HANDS AND FEET	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISTAL MYOTILINOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heart failure	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Limb-Girdle Muscular Dystrophy, Dominant	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MUSCULAR DYSTROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myofibrillar Myopathy, Dominant	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-NEOPLASTIC PERIPHERAL NERVOUS SYSTEM DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL NERVOUS SYSTEM DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL NEUROPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY CARDIOMYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Atrial Fibrillation	Atrial Fibrillation	CTD_human_DG	30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal dominant limb-girdle muscular dystrophy type 1A	Limb-girdle muscular dystrophy	Orphanet			★☆☆☆☆ Found in Text Mining only
Cardiac defects	Cardiac Defects	BEFREE	9537420		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	LHGDN	15111675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathies	Cardiomyopathy	CTD_human_DG	15111675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathies	Cardiomyopathy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathies, Primary	Cardiomyopathy	CTD_human_DG	15111675		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Hypertrophic	Hypertrophic cardiomyopathy	Pubtator	19027924	Associate	★☆☆☆☆ Found in Text Mining only
Central Core Myopathy (disorder)	Myopathy	BEFREE	12899871		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Distal amyotrophy	Distal amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Distal amyotrophy	Distal amyotrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Distal Muscular Dystrophies	Distal Muscular Dystrophy	LHGDN	16674563		★☆☆☆☆ Found in Text Mining only
Distal Muscular Dystrophies	Distal Muscular Dystrophy	BEFREE	17698502, 19027924, 19590214		★☆☆☆☆ Found in Text Mining only
Distal Myopathies	Distal myopathy	Pubtator	19027924, 19590214	Associate	★☆☆☆☆ Found in Text Mining only
Distal myotilinopathy	Distal Myotilinopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	10191080		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	24361111		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophies, Limb-Girdle	Limb-Girdle Muscular Dystrophy	BEFREE	10191080, 10369880, 10958653, 11699871, 12428213, 12499399, 15111675, 15947064, 16076904, 16122733, 16684602, 16801328, 17021404, 17339125, 18335471, 19458539, 21336781, 21376592, 23622359, 31066050, 8533766, 8899051, 9694248, 9828127		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophies, Limb-Girdle	Limb-Girdle Muscular Dystrophy	LHGDN	12428213, 12499399, 16380616, 16801328		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophies, Limb-Girdle	Limb-Girdle Muscular Dystrophy	CTD_human_DG	21336781		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophies, Limb-Girdle	Limb-Girdle Muscular Dystrophy	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy	Muscular dystrophy	BEFREE	12428213, 16122733, 16684602, 16801328		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myocardial Diseases, Secondary	Myocardial Diseases	CTD_human_DG	15111675		★☆☆☆☆ Found in Text Mining only
Myofibrillar Myopathy	Myofibrillar myopathy	BEFREE	14711882, 15111675, 15367857, 15668942, 15752755, 15947064, 16076904, 16122733, 16684602, 16793270, 16801328, 17337483, 17784878, 18769253, 19151983, 21361873, 21676617, 22349301, 22961544, 24361111, 24928145		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myofibrillar Myopathy	Myofibrillar myopathy	Pubtator	15947064, 17418574, 17784878, 19027924, 19050726, 21676617, 22106715, 25208129, 27618136, 27854214, 31309175, 39973468	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myofibrillar Myopathy	Myofibrillar myopathy	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myofibrillar Myopathy	Myofibrillar myopathy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Myopathies, Nemaline	Myopathy	BEFREE	12899871		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	15367857, 15752755, 16674563, 16684602, 17698502, 19590214, 26842778		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	LHGDN	16380616, 16801328		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
MYOPATHY, DISTAL 2	MYOPATHY	BEFREE	16674563		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOFIBRILLAR, 3	Myofibrillar myopathy	UNIPROT_DG	10958653, 12428213, 15111675		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOFIBRILLAR, 3	Myofibrillar myopathy	CLINVAR_DG	10958653, 12428213, 15111675, 15947064, 16684602, 16793270, 16801328, 19225410, 19590214, 21361873, 21676617, 22349301, 25208129, 26342832, 26842778, 27854214, 3275904, 9027924		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOFIBRILLAR, 3	Myofibrillar myopathy	BEFREE	15111675, 15947064, 19027924, 21361873, 26842778		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOFIBRILLAR, 3	Myofibrillar myopathy	ORPHANET_DG	15111675, 16793270, 21361873		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOFIBRILLAR, 3	Myofibrillar myopathy	GENOMICS_ENGLAND_DG	15111675		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOFIBRILLAR, 3	Myofibrillar myopathy	CTD_human_DG	15111675		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10486214		★☆☆☆☆ Found in Text Mining only
Neuromuscular Diseases	Neuromuscular Diseases	BEFREE	19878039		★☆☆☆☆ Found in Text Mining only
NONAKA MYOPATHY	Inclusion body myopathy	BEFREE	15367857		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	28611294	Associate	★☆☆☆☆ Found in Text Mining only
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	CTD_human_DG	30061737		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	15111675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peripheral Nervous System Diseases	Nervous System Diseases	CTD_human_DG	15111675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	15111675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peripheral Neuropathy	Peripheral Neuropathy	LHGDN	15111675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polyneuropathies	Polyneuropathy	Pubtator	25208129	Associate	★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Proximal amyotrophy	Amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	BEFREE	21336781		★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	GENOMICS_ENGLAND_DG	15111675		★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	BEFREE	16380616, 16801328		★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	ORPHANET_DG	16380616		★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	UNIPROT_DG	16380616		★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	Orphanet			★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Spheroid body myopathy	Spheroid Body Myopathy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Vacuolar myopathy	Vacuolar myopathy	Pubtator	32419263	Associate	★☆☆☆☆ Found in Text Mining only