TRIM5

protein-coding

tripartite motif containing 5, 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, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

MANE transcript

NM_033034.3

Inheritance

—

ClinVar variants

U:67B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr11:5,663,195-5,938,619

External References & Databases

Ensembl (ENSG00000132256)

Transcript & Mutation Effects

hg38 • Region Span ~275.4 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 TRIM5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033034.3. 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			2 clinvar		1 clinvar	3
missense			60 clinvar	9 clinvar	1 clinvar	70
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	67	9	2	78

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033034.3	RefSeq	NP_149023.2	7	MANE Select
ENST00000380034.8	Ensembl	ENSP00000369373.3	7	MANE Select
NM_001410958.1	RefSeq	NP_001397887.1	6	Standard
NM_033092.4	RefSeq	NP_149083.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
Cytokine Signaling in Immune system
Immune System
Interferon gamma signaling
Interferon Signaling

Biological Process

activation of innate immune response
pattern recognition receptor signaling pathway
autophagy
viral process
regulation of lipopolysaccharide-mediated signaling pathway

Molecular Function

ubiquitin-protein transferase activity
protein binding
zinc ion binding
signaling pattern recognition receptor activity
protein kinase binding

Cellular Component

P-body
nucleus
cytoplasm
cytosol
omegasome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380034
Coding exons: 7
Length: 275425
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.475	290	268	1.08	0.0000140	3235
Missense (PolyPhen)		65	76.41	0.85068		947
Synonymous	-0.463	107	101	1.06	0.00000533	939
Loss of Function	1.53	9	15.5	0.580	7.24e-7	184

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00087	0.00087	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF- kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by N-tropic murine leukemia virus (N-MLV), equine infectious anemia virus (EIAV), simian immunodeficiency virus of macaques (SIVmac), feline immunodeficiency virus (FIV), and bovine immunodeficiency virus (BIV) (PubMed:17156811). Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (PubMed:25127057). Also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction (PubMed:25127057). {ECO:0000269|PubMed:12878161, ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:18312418, ECO:0000269|PubMed:21035162, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:21632761, ECO:0000269|PubMed:22291694, ECO:0000269|PubMed:25127057}.;

Recessive Scores

pRec: 0.0951

Intolerance Scores

LoFtool: 0.531
RVIS EVS: 1.2
RVIS percentile EVS: 93.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.329

Gene Damage Prediction

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