TRIM63

tripartite motif containing 63, the group of Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): 1:26051300-26068436

Previous symbols: [ "RNF28" ]

Links

ENSG00000158022 ∙ NCBI:84676 ∙ OMIM:606131 ∙ HGNC:16007 ∙ Uniprot:Q969Q1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy (Moderate), mode of inheritance: AR
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIM63 gene.

• Hypertrophic cardiomyopathy (1 variants)
• Inborn genetic diseases (1 variants)
• Idiopathic cardiomyopathy (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM63 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	3	9
missense			36	4		40
nonsense	1					1
start loss						0
frameshift	1		2			3
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			1	3	1	5
non coding				2	15	17
Total	2	0	40	12	18

Highest pathogenic variant AF is 0.0000328

Variants in TRIM63

This is a list of pathogenic ClinVar variants found in the TRIM63 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-26051871-C-T		not specified	Conflicting classifications of pathogenicity (Apr 26, 2023)
1-26051902-TAC-T		not specified	Likely benign (Dec 04, 2023)
1-26053892-C-T		Hypertrophic cardiomyopathy	Uncertain significance (May 06, 2021)
1-26053903-C-T		not specified • TRIM63-related disorder	Benign (Apr 17, 2023)
1-26053931-T-G		Inborn genetic diseases	Uncertain significance (May 26, 2024)
1-26053980-A-G		not specified	Likely benign (Nov 06, 2023)
1-26054237-C-CT			Benign (Sep 04, 2018)
1-26057127-C-G			Benign (May 21, 2021)
1-26057154-CCAGGGGT-C			Benign (Jun 29, 2020)
1-26057217-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
1-26057220-G-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
1-26057221-C-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
1-26057231-G-A		not specified	Likely benign (Aug 19, 2023)
1-26057282-C-G		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
1-26057293-TC-T			Uncertain significance (Jan 17, 2020)
1-26057316-G-A		not specified	Uncertain significance (May 24, 2023)
1-26057325-A-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
1-26057334-G-C			Likely benign (May 04, 2023)
1-26057384-A-G			Benign (Sep 04, 2018)
1-26057522-A-G			Benign (Sep 04, 2018)
1-26058199-T-G			Benign (Sep 04, 2018)
1-26058388-A-C		TRIM63-related disorder	Uncertain significance (Jun 13, 2023)
1-26058416-C-T		not specified	Likely benign (May 01, 2024)
1-26058436-G-A		Inborn genetic diseases	Uncertain significance (Jun 13, 2024)
1-26058482-G-A		Primary familial hypertrophic cardiomyopathy • Inborn genetic diseases • Hypertrophic cardiomyopathy	Conflicting classifications of pathogenicity (Mar 21, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIM63	protein_coding	protein_coding	ENST00000374272	9	17133

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.30e-13	0.0259	125511	0	237	125748	0.000943

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.177	212	205	1.03	0.0000117	2354
Missense in Polyphen		94	85.516	1.0992		889
Synonymous	-0.414	85	80.3	1.06	0.00000480	618
Loss of Function	-0.00863	19	19.0	1.00	8.73e-7	225

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000983	0.000980
Ashkenazi Jewish	0.00804	0.00807
East Asian	0.000163	0.000163
Finnish	0.000787	0.000786
European (Non-Finnish)	0.000829	0.000827
Middle Eastern	0.000163	0.000163
South Asian	0.000236	0.000229
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: 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 provide other organs with amino acids. Inhibits de novo skeletal muscle protein synthesis under amino acid starvation. Regulates proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins. May play a role in striated muscle atrophy and hypertrophy by regulating an anti- hypertrophic PKC-mediated signaling pathway. May regulate the organization of myofibrils through TTN in muscle cells. {ECO:0000269|PubMed:11927605, ECO:0000269|PubMed:18222470}.
• Pathway: TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.628
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.85

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.520
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.905

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trim63
• Phenotype: liver/biliary system phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: muscle contraction;signal transduction;negative regulation of cardiac muscle hypertrophy;skeletal muscle atrophy;response to electrical stimulus involved in regulation of muscle adaptation;protein ubiquitination;response to glucocorticoid;response to interleukin-1
• Cellular component: nucleus;cytoplasm;microtubule;Z disc;M band
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding;titin binding