TRIM63 (tripartite motif containing 63)

Gene

• Entrez ID: 84676
• Gene name: Tripartite motif containing 63
• Gene symbol: TRIM63
• Synonyms (NCBI Gene): CMH31, IRF, MURF1, MURF2, RNF28, SMRZ
• Chromosome: 1
• Chromosome location: 1p36.11
• Summary: This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is an E3 ubiquitin ligase that localizes to the Z-line and M-line lattices of myofibrils. This protein plays an important role in

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs148395034	G>A,C	Likely-pathogenic, uncertain-significance, likely-benign	Stop gained, missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005909	hsa-miR-29a-3p	qRT-PCR	21169019
MIRT017998	hsa-miR-335-5p	Microarray	18185580
MIRT645501	hsa-miR-490-3p	HITS-CLIP	23824327
MIRT645499	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT645500	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT645498	hsa-miR-6734-3p	HITS-CLIP	23824327
MIRT645497	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT645496	hsa-miR-130b-5p	HITS-CLIP	23824327
MIRT645495	hsa-miR-6730-3p	HITS-CLIP	23824327
MIRT645494	hsa-miR-3660	HITS-CLIP	23824327
MIRT645493	hsa-miR-4526	HITS-CLIP	23824327
MIRT645492	hsa-miR-6719-3p	HITS-CLIP	23824327
MIRT645491	hsa-miR-516a-3p	HITS-CLIP	23824327
MIRT645490	hsa-miR-516b-3p	HITS-CLIP	23824327
MIRT645489	hsa-miR-7162-5p	HITS-CLIP	23824327
MIRT645488	hsa-miR-6815-3p	HITS-CLIP	23824327
MIRT645487	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT645486	hsa-miR-6868-3p	HITS-CLIP	23824327
MIRT645485	hsa-miR-4256	HITS-CLIP	23824327
MIRT645484	hsa-miR-4762-3p	HITS-CLIP	23824327
MIRT645501	hsa-miR-490-3p	HITS-CLIP	23824327
MIRT645499	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT645500	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT645498	hsa-miR-6734-3p	HITS-CLIP	23824327
MIRT645497	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT645496	hsa-miR-130b-5p	HITS-CLIP	23824327
MIRT645495	hsa-miR-6730-3p	HITS-CLIP	23824327
MIRT645494	hsa-miR-3660	HITS-CLIP	23824327
MIRT645493	hsa-miR-4526	HITS-CLIP	23824327
MIRT645492	hsa-miR-6719-3p	HITS-CLIP	23824327
MIRT645491	hsa-miR-516a-3p	HITS-CLIP	23824327
MIRT645490	hsa-miR-516b-3p	HITS-CLIP	23824327
MIRT645489	hsa-miR-7162-5p	HITS-CLIP	23824327
MIRT645488	hsa-miR-6815-3p	HITS-CLIP	23824327
MIRT645487	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT645486	hsa-miR-6868-3p	HITS-CLIP	23824327
MIRT645485	hsa-miR-4256	HITS-CLIP	23824327
MIRT645484	hsa-miR-4762-3p	HITS-CLIP	23824327
MIRT1455602	hsa-miR-1287	CLIP-seq
MIRT1455603	hsa-miR-23a	CLIP-seq
MIRT1455604	hsa-miR-23b	CLIP-seq
MIRT1455605	hsa-miR-23c	CLIP-seq
MIRT1455606	hsa-miR-300	CLIP-seq
MIRT1455607	hsa-miR-3135b	CLIP-seq
MIRT1455608	hsa-miR-346	CLIP-seq
MIRT1455609	hsa-miR-381	CLIP-seq
MIRT1455610	hsa-miR-4288	CLIP-seq
MIRT1455611	hsa-miR-4302	CLIP-seq
MIRT1455612	hsa-miR-4666-3p	CLIP-seq
MIRT1455613	hsa-miR-4710	CLIP-seq
MIRT1455614	hsa-miR-4789-5p	CLIP-seq
MIRT1455615	hsa-miR-4795-3p	CLIP-seq
MIRT1455616	hsa-miR-548c-3p	CLIP-seq
MIRT1455617	hsa-miR-632	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004842	Function	Ubiquitin-protein transferase activity	IEA
GO:0005515	Function	Protein binding	IPI	18157088, 23414517, 31391242, 32296183
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	11927605
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	NAS	11243782
GO:0005874	Component	Microtubule	NAS	11243782
GO:0006936	Process	Muscle contraction	IEA
GO:0007165	Process	Signal transduction	NAS	11243782
GO:0008270	Function	Zinc ion binding	IEA
GO:0010614	Process	Negative regulation of cardiac muscle hypertrophy	IEA
GO:0014732	Process	Skeletal muscle atrophy	IEA
GO:0014878	Process	Response to electrical stimulus involved in regulation of muscle adaptation	IEA
GO:0014878	Process	Response to electrical stimulus involved in regulation of muscle adaptation	ISS
GO:0016567	Process	Protein ubiquitination	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0030018	Component	Z disc	IEA
GO:0031430	Component	M band	IEA
GO:0031432	Function	Titin binding	IDA	11927605
GO:0043292	Component	Contractile muscle fiber	IEA
GO:0045087	Process	Innate immune response	IBA
GO:0045820	Process	Negative regulation of glycolytic process	IMP	34244144
GO:0046872	Function	Metal ion binding	IEA
GO:0051384	Process	Response to glucocorticoid	IEA
GO:0061630	Function	Ubiquitin protein ligase activity	IBA
GO:0061630	Function	Ubiquitin protein ligase activity	IDA	34244144
GO:0061630	Function	Ubiquitin protein ligase activity	IEA
GO:0070555	Process	Response to interleukin-1	IEA

Other IDs

• MIM: 606131
• HGNC: 16007
• e!Ensembl: ENSG00000158022

Protein

• UniProt ID: Q969Q1
• Protein name: E3 ubiquitin-protein ligase TRIM63 (EC 2.3.2.27) (Iris RING finger protein) (Muscle-specific RING finger protein 1) (MuRF-1) (MuRF1) (RING finger protein 28) (RING-type E3 ubiquitin transferase TRIM63) (Striated muscle RING zinc finger protein) (Tripartit
• Protein function: E3 ubiquitin ligase. Mediates the ubiquitination and subsequent proteasomal degradation of CKM, GMEB1 and HIBADH. Regulates the proteasomal degradation of muscle proteins under amino acid starvation, where muscle protein is catabolized to provid
• PDB: 2D8U, 3DDT, 4M3L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13445	zf-RING_UBOX	23 → 76	RING-type zinc-finger	Domain
  PF00643	zf-B_box	118 → 159	B-box zinc finger	Domain

• Tissue specificity: TISSUE SPECIFICITY: Muscle specific. Selectively expressed in heart and skeletal muscle. Also expressed in the iris. {ECO:0000269|PubMed:11243782, ECO:0000269|PubMed:11283016, ECO:0000269|PubMed:11679633, ECO:0000269|PubMed:12107412}.
• Sequence:

  MDYKSSLIQDGNPMENLEKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWT
  SRGSSVSMSGGRFRCPTCRHEVIMDRHGVYGLQRNLLVENIIDIYKQECSSRPLQKGSHP
  MCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQSVFQGQKTELNNCISMLVAG
  NDRVQTIITQLEDSRRVTKENSHQVKEELSQKFDTLYAILDEKKSELLQRITQEQEKKLS
  FIEALIQQYQEQLDKSTKLVETAIQSLDEPGGATFLLTAKQLIKSIVEASKGCQLGKTEQ
  GFENMDFFTLDLEHIADALRAIDFGTDEEEEEFIEEEDQEEEESTEGKEEGHQ

• Sequence length: 353

Pathways

KEGG:

Cytoskeleton in muscle cells

Reactome:

Antigen processing: Ubiquitination & Proteasome degradation

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
Cardiomyopathy, familial hypertrophic, 31	Pathogenic	rs540072010	RCV005606795	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypertrophic cardiomyopathy	Pathogenic	rs540072010	RCV001533452	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Idiopathic cardiomyopathy	Pathogenic	rs750765152	RCV003985950	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATROPHY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMEGALY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHY, HYPERTROPHIC, FAMILIAL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiovascular phenotype	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY CARDIOMYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary familial hypertrophic cardiomyopathy	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRIM63-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alveolar Soft Part Sarcoma	Alveolar Sarcoma	BEFREE	21552147		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	Pubtator	33782480	Associate	★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	16916907, 18240972, 22518834, 24704539, 27526027, 35806119, 37021483, 37335026	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	31399258		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	20507321	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	33854184	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomegaly	Cardiomegaly	Pubtator	30372688	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathies	Cardiomyopathy	CTD_human_DG	19168726		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathies	Cardiomyopathy	Pubtator	32451364	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cardiomyopathies, Primary	Cardiomyopathy	CTD_human_DG	19168726		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Hypertrophic	Hypertrophic cardiomyopathy	Pubtator	24865491, 32451364, 37431535, 38002985, 39971408	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Restrictive	Restrictive cardiomyopathy	Pubtator	32451364	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular Disorders	Cerebrovascular disorder	Pubtator	32451364	Associate	★☆☆☆☆ Found in Text Mining only
Chronic heart failure	Heart Failure	BEFREE	30462567, 31140761		★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	28392400, 28506762, 30043444		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	21750087		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	LHGDN	17478621		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	20965933		★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	23432902		★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	30462567, 31140761		★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	29538462		★☆☆☆☆ Found in Text Mining only
Crisponi syndrome	Crisponi syndrome	Pubtator	26329309	Associate	★☆☆☆☆ Found in Text Mining only
Critical Illness	Critical illness	Pubtator	21483870	Associate	★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	29709011, 31243648		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	18468620, 28000044, 30510624		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	18468620, 28000044, 29497304, 30510624		★☆☆☆☆ Found in Text Mining only
Diabetic Cardiomyopathies	Diabetic cardiomyopathy	Pubtator	37355664	Stimulate	★☆☆☆☆ Found in Text Mining only
Dysferlinopathy	Dysferlinopathy	BEFREE	24395438		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	BEFREE	21192842		★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	30217537		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	30372688	Associate	★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	BEFREE	18468620		★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	CLINGEN_DG	11679633, 15601779, 22821932, 25801283		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	22821932, 24436435, 24865491, 31628103		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	GENOMICS_ENGLAND_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypertrophic obstructive cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	22821932, 24436435, 24865491		★☆☆☆☆ Found in Text Mining only
Hypertrophy	Hypertrophy	Pubtator	16916907	Stimulate	★☆☆☆☆ Found in Text Mining only
Hypertrophy Left Ventricular	Left ventricular disease	Pubtator	32451364	Associate	★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	21305677		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	34952945	Associate	★☆☆☆☆ Found in Text Mining only
leiomyosarcoma	Leiomyosarcoma	BEFREE	21192842		★☆☆☆☆ Found in Text Mining only
Leiomyosarcoma	Leiomyosarcoma	Pubtator	21192842	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	11289138		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	23432902		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	30697967	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	18050197	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	18050197		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	34952945	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Fibrous Histiocytoma	Malignant Histiocytoma	BEFREE	29493231		★☆☆☆☆ Found in Text Mining only
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	30217537		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31399258		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	29852290		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25093807		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	Pubtator	23432902	Stimulate	★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	28758352		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	26489459	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	10626142, 18922617, 21454650		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	9204971		★☆☆☆☆ Found in Text Mining only
Myocardial Diseases, Secondary	Myocardial Diseases	CTD_human_DG	19168726		★☆☆☆☆ Found in Text Mining only
Myocardial Ischemia	Myocardial Ischemia	BEFREE	23690937, 29538462		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	25801283, 29868881, 31140761		★☆☆☆☆ Found in Text Mining only
MYOPATHY, MYOSIN STORAGE (disorder)	Myosin storage myopathy	BEFREE	25801283		★☆☆☆☆ Found in Text Mining only
Myositis	Myositis	BEFREE	28649743		★☆☆☆☆ Found in Text Mining only
Myositis	Myositis	Pubtator	39946176	Associate	★☆☆☆☆ Found in Text Mining only
Myotonic Dystrophy	Myotonic dystrophy	Pubtator	30901379	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	36371985	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	18344867, 21165583, 21552147		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	BEFREE	29777277		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	26329309, 33782480	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis, Postmenopausal	Osteoporosis	BEFREE	26329309		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	29852290		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	35146962	Stimulate	★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Diseases	Vascular Diseases	BEFREE	23690937		★☆☆☆☆ Found in Text Mining only
Peripheral Vascular Diseases	Vascular Diseases	BEFREE	23690937		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	23844868, 27526027	Associate	★☆☆☆☆ Found in Text Mining only
Sarcoma Alveolar Soft Part	Sarcoma	Pubtator	19146682	Associate	★☆☆☆☆ Found in Text Mining only
Sarcopenia	Sarcopenia	Pubtator	35806119	Associate	★☆☆☆☆ Found in Text Mining only
Sjogren's Syndrome	Sjogren syndrome	Pubtator	18050197	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	20507321	Associate	★☆☆☆☆ Found in Text Mining only
Tachycardia Ventricular	Ventricular tachycardia	Pubtator	32451364	Associate	★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular Diseases	BEFREE	22146233		★☆☆☆☆ Found in Text Mining only
Ventricular Dysfunction Left	Ventricular dysfunction	Pubtator	32451364	Associate	★☆☆☆☆ Found in Text Mining only