TRIM56
protein-codingtripartite motif containing 56, the group of Tripartite motif family|Ring finger proteins
Gene summary
Enables ubiquitin protein ligase activity. Involved in defense response to virus; positive regulation of signal transduction; and protein monoubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.5 kbGenCC 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 TRIM56 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030961.3. 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 | 1 | 2 | |||
| missense | 129 | 8 | 1 | 138 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 129 | 9 | 2 | 140 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_112223.1 | 1 | MANE Select | |
| Ensembl | ENSP00000305161.6 | 1 | MANE Select | |
| Ensembl | ENSP00000404186.1 | 2 | Standard | |
| Ensembl | ENSP00000486217.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of innate immune responses to cytosolic DNA
- Innate Immune System
- Immune System
- Cytosolic sensors of pathogen-associated DNA
Biological Process
- regulation of type I interferon production
- interferon-beta production
- response to type I interferon
- defense response to virus
- protein K63-linked ubiquitination
Molecular Function
- RNA binding
- ubiquitin-protein transferase activity
- zinc ion binding
Cellular Component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306085
- Coding exons
- 1
- Length
- 6298
- Individuals with no LoFs
- 124773
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 124805
- p
- 0.000128
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 397 | 474 | 0.838 | 0.0000330 | 4731 |
| Missense (PolyPhen) | 131 | 200.34 | 0.65387 | 1998 | ||
| Synonymous | -0.887 | 235 | 218 | 1.08 | 0.0000152 | 1698 |
| Loss of Function | 1.89 | 9 | 17.5 | 0.513 | 8.99e-7 | 209 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000064 | rare |
| Latino/Admixed American | 0.000065 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00023 | 0.00021 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity (PubMed:21289118). In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets TMEM173/STING to 'Lys-63'-linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta (By similarity). Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling. Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES. Promotes establishment of an antiviral state by TLR3 ligand and TLR3-mediated chemokine induction following infection by hepatitis C virus (PubMed:22948160). {ECO:0000250|UniProtKB:Q80VI1, ECO:0000269|PubMed:21289118, ECO:0000269|PubMed:22948160}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.743
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |