TRIM8

tripartite motif containing 8, the group of Tripartite motif family|Ring finger proteins

Basic information

Region (hg38): 10:102642503-102662789

Previous symbols: [ "RNF27" ]

Links

ENSG00000171206 ∙ NCBI:81603 ∙ OMIM:606125 ∙ HGNC:15579 ∙ Uniprot:Q9BZR9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• genetic developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
• focal segmental glomerulosclerosis and neurodevelopmental syndrome (Strong), mode of inheritance: AD
• focal segmental glomerulosclerosis and neurodevelopmental syndrome (Definitive), mode of inheritance: AD
• focal segmental glomerulosclerosis and neurodevelopmental syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal segmental glomerulosclerosis and neurodevelopmental syndrome	AD	Renal	Among other features, the condition can include renal disease, and awareness may allow early diagnosis and management	Craniofacial; Musculoskeletal; Renal	23934111; 27346735; 30244534; 32193649; 32531461; 33508234
Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIM8 gene.

• not_provided (362 variants)
• Inborn_genetic_diseases (38 variants)
• Focal_segmental_glomerulosclerosis_and_neurodevelopmental_syndrome (23 variants)
• TRIM8-related_disorder (13 variants)
• Seizure (9 variants)
• Focal_segmental_glomerulosclerosis (8 variants)
• Neurodevelopmental_delay (8 variants)
• not_specified (3 variants)
• TRIM8-related_epileptic_encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030912.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	120	7	128
missense			149	52	5	206
nonsense	9	6	5			20
start loss			1			1
frameshift	1	4	5			10
splice donor/acceptor (+/-2bp)			1			1
Total	10	10	162	172	12

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIM8	protein_coding	protein_coding	ENST00000302424	6	13912

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00562	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.74	198	340	0.582	0.0000201	3574
Missense in Polyphen		38	95.399	0.39833		1116
Synonymous	1.42	139	162	0.858	0.0000109	1082
Loss of Function	4.18	2	24.2	0.0826	0.00000113	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000288	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase which plays different roles in immune pathways. Participates in the activation of interferon- gamma signaling by promoting proteasomal degradation of the repressor SOCS1 (PubMed:12163497). Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the 'lys-63' polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B (PubMed:22084099, PubMed:23152791). Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus (PubMed:20516148). {ECO:0000269|PubMed:12163497, ECO:0000269|PubMed:20516148, ECO:0000269|PubMed:22084099, ECO:0000269|PubMed:23152791}.
• Pathway: Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.125

Intolerance Scores

• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.31

Haploinsufficiency Scores

• pHI: 0.467
• hipred: Y
• hipred_score: 0.783
• ghis: 0.674

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.776

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trim8

Gene ontology

• Biological process: positive regulation of autophagy;protein ubiquitination;stem cell population maintenance;negative regulation of viral transcription;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;negative regulation of viral entry into host cell;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;interferon-gamma-mediated signaling pathway;positive regulation of protein localization to nucleus;negative regulation of viral release from host cell
• Cellular component: cytosol;PML body
• Molecular function: protein binding;zinc ion binding;transferase activity;identical protein binding;protein homodimerization activity