TRIM21

tripartite motif containing 21, the group of Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): 11:4384896-4393702

Previous symbols: [ "SSA1" ]

Links

ENSG00000132109 ∙ NCBI:6737 ∙ OMIM:109092 ∙ HGNC:11312 ∙ Uniprot:P19474 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIM21 gene.

• Inborn genetic diseases (12 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM21 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				1	2	3
missense			11	1		12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	2	2

Variants in TRIM21

This is a list of pathogenic ClinVar variants found in the TRIM21 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-4385418-G-A		not specified	Uncertain significance (Jan 19, 2024)
11-4385432-G-A			Likely benign (Aug 01, 2022)
11-4385502-G-A		not specified	Uncertain significance (Feb 28, 2023)
11-4385614-C-T		not specified	Uncertain significance (Jan 23, 2024)
11-4385623-G-A		not specified	Uncertain significance (Jun 11, 2021)
11-4385627-A-G			Benign (Jul 18, 2018)
11-4385758-G-A		not specified	Uncertain significance (Jun 29, 2023)
11-4385767-G-T		not specified	Uncertain significance (Mar 13, 2023)
11-4385797-G-A		not specified	Uncertain significance (Oct 12, 2021)
11-4385818-A-G		not specified	Uncertain significance (Feb 22, 2024)
11-4385833-C-T		not specified	Uncertain significance (Apr 07, 2022)
11-4386166-T-A		not specified	Uncertain significance (Jan 03, 2024)
11-4386167-C-A		not specified	Uncertain significance (Nov 14, 2023)
11-4386983-A-G		not specified	Uncertain significance (Sep 30, 2021)
11-4388317-C-T		not specified	Uncertain significance (Apr 06, 2023)
11-4389679-A-G		not specified	Uncertain significance (Apr 26, 2023)
11-4389704-A-G			Benign (Aug 15, 2017)
11-4390040-C-T		not specified	Likely benign (Dec 22, 2023)
11-4390135-C-T		not specified	Uncertain significance (Apr 13, 2022)
11-4390138-C-T		not specified	Likely benign (Sep 16, 2021)
11-4390318-C-A		not specified	Uncertain significance (Jul 12, 2022)
11-4390331-C-T		not specified	Likely benign (Dec 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIM21	protein_coding	protein_coding	ENST00000254436	6	8800

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.35e-9	0.529	124621	0	36	124657	0.000144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.292	266	253	1.05	0.0000131	3106
Missense in Polyphen		70	84.618	0.82725		1120
Synonymous	-2.68	129	95.6	1.35	0.00000469	916
Loss of Function	1.12	16	21.6	0.740	0.00000107	240

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000282	0.000281
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000561	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.000227	0.000221
Middle Eastern	0.0000561	0.0000556
South Asian	0.0000983	0.0000980
Other	0.000168	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination. Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)- like complex is shown to mediate ubiquitination of CDKN1B ('Thr- 187' phosphorylated-form), thereby promoting its degradation by the proteasome. Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling. Negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin- mediated degradation of IRF3. Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway. Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages. Plays a role in the regulation of the cell cycle progression. Enhances the decapping activity of DCP2. Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules. At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified. The common feature of these proteins is their ability to bind HY RNAs.2. Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of IRF3, hence attenuating type I interferon (IFN)-dependent immune responses (PubMed:26347139). {ECO:0000269|PubMed:16297862, ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:16880511, ECO:0000269|PubMed:18022694, ECO:0000269|PubMed:18361920, ECO:0000269|PubMed:18641315, ECO:0000269|PubMed:18845142, ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:26347139}.
• Pathway: Systemic lupus erythematosus - Homo sapiens (human);Cytokine Signaling in Immune system;STING mediated induction of host immune responses;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;Interferon gamma signaling;Cytosolic sensors of pathogen-associated DNA ;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.434
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• pHI: 0.366
• hipred: Y
• hipred_score: 0.546
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trim21
• 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; immune system phenotype; renal/urinary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: protein polyubiquitination;protein monoubiquitination;cell cycle;positive regulation of autophagy;protein ubiquitination;protein destabilization;negative regulation of NF-kappaB transcription factor activity;regulation of type I interferon production;negative regulation of viral transcription;response to interferon-gamma;innate immune response;positive regulation of cell cycle;positive regulation of viral entry into host cell;positive regulation of DNA-binding transcription factor activity;protein autoubiquitination;interferon-gamma-mediated signaling pathway;protein trimerization;negative regulation of protein deubiquitination;negative regulation of viral release from host cell
• Cellular component: P-body;nucleus;nucleoplasm;cytoplasm;autophagosome;cytosol;SCF ubiquitin ligase complex;cytoplasmic vesicle;ribonucleoprotein complex
• Molecular function: DNA binding;RNA binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;identical protein binding