TRIM32

tripartite motif containing 32, the group of Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): 9:116687304-116701300

Previous symbols: [ "LGMD2H" ]

Links

ENSG00000119401 ∙ NCBI:22954 ∙ OMIM:602290 ∙ HGNC:16380 ∙ Uniprot:Q13049 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 11 (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2H (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2H (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 11 (Strong), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2H (Strong), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 11	AR	Endocrine	Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	4269389; 10399877; 11822024; 15886712; 15580560; 16243356; 15786463; 16606853; 17994549; 19492423; 20301537; 20177705; 21775502; 22981120; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIM32 gene.

• Bardet-Biedl syndrome (461 variants)
• not provided (185 variants)
• Sarcotubular myopathy (78 variants)
• Bardet-Biedl syndrome 11 (73 variants)
• Bardet-Biedl syndrome 11;Sarcotubular myopathy (44 variants)
• Sarcotubular myopathy;Bardet-Biedl syndrome 11 (41 variants)
• TRIM32-related condition (29 variants)
• not specified (25 variants)
• Inborn genetic diseases (20 variants)
• Autosomal recessive limb-girdle muscular dystrophy (2 variants)
• Limb-Girdle Muscular Dystrophy, Recessive (2 variants)
• Limb-girdle muscular dystrophy (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM32 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			10	141	1	152
missense	1	2	291	2		296
nonsense	9	5	2			16
start loss						0
frameshift	14	11				25
inframe indel			5			5
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			31	2	7	40
Total	24	18	339	145	8

Highest pathogenic variant AF is 0.0000131

Variants in TRIM32

This is a list of pathogenic ClinVar variants found in the TRIM32 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-116687320-C-T		Sarcotubular myopathy • Bardet-Biedl syndrome 11	Uncertain significance (Jan 13, 2018)
9-116687330-G-C		Sarcotubular myopathy • Bardet-Biedl syndrome 11	Benign (Jul 03, 2018)
9-116687339-G-A		Bardet-Biedl syndrome 11 • Sarcotubular myopathy	Uncertain significance (Jan 12, 2018)
9-116687354-T-C		Bardet-Biedl syndrome 11 • Sarcotubular myopathy	Uncertain significance (Jan 13, 2018)
9-116687369-C-T		not specified	Likely benign (Sep 19, 2017)
9-116687467-C-T			Benign (Apr 11, 2019)
9-116697371-A-G			Likely benign (Dec 02, 2019)
9-116697564-G-A			Benign (Jun 16, 2018)
9-116697737-A-G		TRIM32-related disorder	Likely benign (Dec 08, 2021)
9-116697738-G-A		TRIM32-related disorder	Conflicting classifications of pathogenicity (Jan 28, 2020)
9-116697748-T-G		Bardet-Biedl syndrome • not specified	Conflicting classifications of pathogenicity (Jan 30, 2024)
9-116697753-C-T		Bardet-Biedl syndrome	Uncertain significance (Aug 10, 2022)
9-116697757-A-C		Bardet-Biedl syndrome	Likely benign (May 19, 2023)
9-116697762-C-T		Bardet-Biedl syndrome • TRIM32-related disorder	Uncertain significance (Oct 26, 2023)
9-116697763-T-A		Bardet-Biedl syndrome	Likely benign (Oct 17, 2023)
9-116697766-C-A		Bardet-Biedl syndrome	Uncertain significance (Aug 23, 2022)
9-116697769-G-A		Bardet-Biedl syndrome	Likely benign (Nov 03, 2022)
9-116697769-G-C		Bardet-Biedl syndrome • Sarcotubular myopathy • Bardet-Biedl syndrome 11	Conflicting classifications of pathogenicity (Jan 27, 2024)
9-116697769-G-T		Bardet-Biedl syndrome	Likely benign (Jul 17, 2023)
9-116697774-T-C		Bardet-Biedl syndrome • Sarcotubular myopathy;Bardet-Biedl syndrome 11 • TRIM32-related disorder • Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
9-116697782-C-G			Uncertain significance (Jun 30, 2020)
9-116697782-C-T		Bardet-Biedl syndrome	Uncertain significance (May 21, 2022)
9-116697784-C-A		Bardet-Biedl syndrome	Likely benign (May 02, 2023)
9-116697785-C-T		Bardet-Biedl syndrome	Uncertain significance (Mar 02, 2022)
9-116697786-G-A		Bardet-Biedl syndrome	Uncertain significance (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIM32	protein_coding	protein_coding	ENST00000450136	1	13999

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00167	0.974	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.827	335	380	0.881	0.0000245	4253
Missense in Polyphen		93	125.72	0.73972		1505
Synonymous	0.619	134	143	0.934	0.00000746	1392
Loss of Function	1.98	7	15.4	0.455	8.06e-7	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000536	0.000535
Ashkenazi Jewish	0.000596	0.000595
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000272	0.000272
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has an E3 ubiquitin ligase activity. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May ubiquitinate BBS2. May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo. {ECO:0000269|PubMed:19349376, ECO:0000269|PubMed:22500027}.
• Disease: DISEASE: Limb-girdle muscular dystrophy 2H (LGMD2H) [MIM:254110]: An autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life. {ECO:0000269|PubMed:11822024, ECO:0000269|PubMed:17994549}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bardet-Biedl syndrome 11 (BBS11) [MIM:615988]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:16606853}. Note=The disease is caused by mutations affecting the gene represented in this entry. It has been suggested that TRIM32 might be the E3 ubiquitin ligase for BBS2, a component of the BBSome complex involved in ciliogenesis, that is ubiquitinated and degraded by the proteasome (PubMed:22500027). {ECO:0000269|PubMed:22500027}.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Regulation of innate immune responses to cytosolic DNA;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;TNFalpha;Cytosolic sensors of pathogen-associated DNA (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.211
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.239
• hipred: Y
• hipred_score: 0.757
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trim32
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: trim32
• Affected structure: pronephric duct
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: protein polyubiquitination;tissue homeostasis;ubiquitin-dependent protein catabolic process;actin ubiquitination;response to UV;protein ubiquitination;positive regulation of cell growth;positive regulation of cell migration;regulation of type I interferon production;negative regulation of viral transcription;response to tumor necrosis factor;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;fat cell differentiation;positive regulation of neuron differentiation;positive regulation of protein catabolic process;positive regulation of cell cycle;positive regulation of proteolysis;muscle cell cellular homeostasis;negative regulation of fibroblast proliferation;positive regulation of neurogenesis;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;positive regulation of striated muscle cell differentiation;axon development;protein K48-linked ubiquitination;negative regulation of viral release from host cell;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;positive regulation of tumor necrosis factor-mediated signaling pathway;positive regulation of nucleic acid-templated transcription;positive regulation of interleukin-17-mediated signaling pathway;positive regulation of chemokine (C-C motif) ligand 20 production;positive regulation of cell motility
• Cellular component: nucleus;cytoplasm;cytosol;striated muscle myosin thick filament
• Molecular function: transcription coactivator activity;RNA binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;myosin binding;Tat protein binding;translation initiation factor binding;identical protein binding;ubiquitin binding;protein self-association;ubiquitin protein ligase activity