TRIM6

protein-coding

tripartite motif containing 6, the group of Tripartite motif family|Ring finger proteins

Gene summary

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, B-box type 1 and B-box type 2 domain, and a coiled-coil region. The protein localizes to the nucleus, but its specific function has not been identified. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. Alternative splicing results in multiple transcript variants. A read-through transcript from this gene into the downstream TRIM34 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]

MANE transcript

NM_001003818.3

Inheritance

—

ClinVar variants

U:40B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr11:5,596,109-5,612,958

External References & Databases

Ensembl (ENSG00000121236)

Transcript & Mutation Effects

hg38 • Region Span ~16.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRIM6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001003818.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			40 clinvar	2 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	40	3	0	43

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001003818.3	RefSeq	NP_001003818.1	8	MANE Select
ENST00000380097.8	Ensembl	ENSP00000369440.3	8	MANE Select
NM_001198644.2	RefSeq	NP_001185573.1	5	Standard
NM_001198645.2	RefSeq	NP_001185574.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine Signaling in Immune system
Immune System
Interferon gamma signaling
Interferon Signaling

Biological Process

protein polyubiquitination
positive regulation of defense response to virus by host
positive regulation of cytokine secretion involved in immune response
positive regulation of gene expression
negative regulation of gene expression

Molecular Function

protein binding
transcription factor binding
zinc ion binding
protein kinase binding
protein binding, bridging

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380097
Coding exons: 8
Length: 16850
Individuals with no LoFs: 125536
Homozygous LoFs: 0
Heterozygous LoFs: 211
Defined: 125747
p: 0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.02	324	276	1.17	0.0000150	3358
Missense (PolyPhen)		90	67.937	1.3247		987
Synonymous	0.288	101	105	0.964	0.00000517	1028
Loss of Function	1.10	22	28.3	0.776	0.00000182	283

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00037	rare
Latino/Admixed American	0.0027	0.0026	notable
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.00049	0.00049	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00096	0.00065	rare
South Asian	0.00046	0.00042	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase which ubiquitinates MYC and inhibits its transcription activation activity, maintaining the pluripotency of embryonic stem cells (By similarity). Involved in the synthesis of unanchored K48-linked polyubiquitin chains which interact with and activate the serine/threonine kinase IKBKE, leading to phosphorylation of STAT1 and stimulation of an antiviral response (PubMed:24882218). {ECO:0000250|UniProtKB:Q8BGE7, ECO:0000269|PubMed:24882218}.;

Recessive Scores

pRec: 0.0811

Intolerance Scores

LoFtool: 0.639
RVIS EVS: 0.51
RVIS percentile EVS: 80.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.605

Gene Damage Prediction

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