TRIM37

tripartite motif containing 37, the group of Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): 17:58982637-59106921

Previous symbols: [ "MUL" ]

Links

ENSG00000108395 ∙ NCBI:4591 ∙ OMIM:605073 ∙ HGNC:7523 ∙ Uniprot:O94972 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mulibrey nanism (Definitive), mode of inheritance: AR
• mulibrey nanism (Strong), mode of inheritance: AR
• mulibrey nanism (Supportive), mode of inheritance: AR
• mulibrey nanism (Strong), mode of inheritance: AR
• mulibrey nanism (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mulibrey nanism	AR	Cardiovascular; Oncologic	Surveillance and early detection of and treatment for malignancy (Wilms tumors, as well a number of other cancer types have been reported) may decrease morbidity and mortality; Awareness of cardiovascular anomalies (including structural anomalies, as well as pericardial constriction and congestive heart failure) may be beneficial in order to allow early diagnosis and treatment	Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	4124529; 135512; 8335020; 10888877; 12754710; 14757854; 15108285; 15590968; 16306379; 17100991; 16310976; 17551331; 19329943; 19334051; 21865362; 23385855
The condition may involve multiple malformations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIM37 gene.

• not provided (325 variants)
• Mulibrey nanism syndrome (138 variants)
• Inborn genetic diseases (33 variants)
• not specified (9 variants)
• TRIM37-related condition (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM37 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			7	76	1	84
missense		1	99	3	1	104
nonsense	8	14				22
start loss						0
frameshift	16	11	1			28
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	13				14
splice region			8	14	1	23
non coding			39	87	31	157
Total	25	39	149	166	33

Highest pathogenic variant AF is 0.000643

Variants in TRIM37

This is a list of pathogenic ClinVar variants found in the TRIM37 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-58982923-T-A		Mulibrey nanism syndrome	Likely pathogenic (May 13, 2019)
17-58982945-C-T			Likely benign (Dec 18, 2019)
17-58998293-G-A		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998317-G-C		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998347-A-G		Mulibrey nanism syndrome	Uncertain significance (Jan 12, 2018)
17-58998348-T-C		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998352-T-C		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998399-TG-T		Mulibrey nanism syndrome	Uncertain significance (Jun 14, 2016)
17-58998414-T-C		Mulibrey nanism syndrome	Uncertain significance (Jan 12, 2018)
17-58998416-T-C		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998452-C-A		Mulibrey nanism syndrome	Uncertain significance (Jan 12, 2018)
17-58998541-T-C		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998618-A-G		Mulibrey nanism syndrome	Likely benign (Jan 12, 2018)
17-58998714-A-G		Mulibrey nanism syndrome	Uncertain significance (Mar 16, 2018)
17-58998719-T-C		Mulibrey nanism syndrome	Likely benign (Jan 13, 2018)
17-58998743-T-A		Mulibrey nanism syndrome	Benign (Jan 12, 2018)
17-58998755-A-G		Mulibrey nanism syndrome	Uncertain significance (Jan 12, 2018)
17-58998779-G-A		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998783-T-C		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998893-C-T		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58998996-A-G		Mulibrey nanism syndrome	Uncertain significance (Jan 12, 2018)
17-58999004-T-C		Mulibrey nanism syndrome	Benign (Jan 13, 2018)
17-58999008-G-A		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)
17-58999033-C-T		Mulibrey nanism syndrome	Uncertain significance (Jan 12, 2018)
17-58999142-C-T		Mulibrey nanism syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIM37	protein_coding	protein_coding	ENST00000262294	24	124284

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.70e-12	1.00	125461	0	287	125748	0.00114

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.820	476	529	0.900	0.0000286	6356
Missense in Polyphen		97	151.53	0.64016		1798
Synonymous	-0.0639	177	176	1.01	0.00000899	1791
Loss of Function	3.85	29	61.6	0.471	0.00000367	685

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000467	0.000467
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000653	0.000653
Finnish	0.00913	0.00914
European (Non-Finnish)	0.000458	0.000448
Middle Eastern	0.000653	0.000653
South Asian	0.000131	0.000131
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase required to prevent centriole reduplication (PubMed:15885686, PubMed:23769972). Probably acts by ubiquitinating positive regulators of centriole reduplication (PubMed:23769972). Mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression: associates with some Polycomb group (PcG) multiprotein PRC2-like complex and mediates repression of target genes (PubMed:25470042). Has anti-HIV activity (PubMed:24317724). {ECO:0000269|PubMed:15885686, ECO:0000269|PubMed:23769972, ECO:0000269|PubMed:24317724, ECO:0000269|PubMed:25470042}.
• Disease: DISEASE: Mulibrey nanism (MUL) [MIM:253250]: An autosomal recessive growth disorder characterized by severe growth failure of prenatal onset, constrictive pericardium and progressive cardiomyopathy, facial dysmorphism, and failure of sexual maturation. Additional clinical features include hepatomegaly, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, hypoplasia of various endocrine glands, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor. {ECO:0000269|PubMed:10888877, ECO:0000269|PubMed:12754710, ECO:0000269|PubMed:15108285, ECO:0000269|PubMed:15885686, ECO:0000269|PubMed:17100991, ECO:0000269|PubMed:17551331, ECO:0000269|PubMed:21865362, ECO:0000269|PubMed:23385855}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.289

Intolerance Scores

• loftool: 0.884
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.54

Haploinsufficiency Scores

• pHI: 0.334
• hipred: Y
• hipred_score: 0.524
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trim37
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; 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); hematopoietic 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); neoplasm; 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); immune system phenotype; skeleton phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;negative regulation of NF-kappaB transcription factor activity;histone H2A monoubiquitination;histone H2A-K119 monoubiquitination;negative regulation of centriole replication;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;protein autoubiquitination;aggresome assembly
• Cellular component: cytoplasm;peroxisome;cytosol;aggresome;ESC/E(Z) complex;perinuclear region of cytoplasm
• Molecular function: chromatin binding;ubiquitin-protein transferase activity;tumor necrosis factor receptor binding;protein binding;zinc ion binding;ubiquitin protein ligase binding;protein homodimerization activity;ubiquitin protein ligase activity