TRIM68
protein-codingtripartite motif containing 68, the group of Tripartite motif family|Ring finger proteins
Gene summary
This gene encodes a member of the tripartite motif-containing protein family, whose members are characterized by a "really interesting new gene" (RING) finger domain, a zinc-binding B-box motif, and a coiled-coil region. Members of this family function as E3 ubiquitin ligases and are involved in a broad range of biological processes. This gene regulates the activation of nuclear receptors, such as androgen receptor, and has been implicated in development of prostate cancer cells, where its expression increases in response to a downregulation of microRNAs. In addition, this gene participates in viral defense regulation as a negative regulator of interferon-beta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
- RNF137
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.6 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 TRIM68 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018073.8. 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 | 0 | |||||
| missense | 92 | 6 | 98 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 92 | 6 | 0 | 98 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060543.5 | 6 | MANE Select | |
| Ensembl | ENSP00000300747.5 | 6 | MANE Select | |
| RefSeq | NP_001291425.1 | 4 | Standard | |
| Ensembl | ENSP00000434681.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cytokine Signaling in Immune system
- Immune System
- AndrogenReceptor
- Interferon gamma signaling
- Interferon Signaling
Biological Process
- protein autoubiquitination
- interferon-gamma-mediated signaling pathway
- regulation of androgen receptor signaling pathway
Molecular Function
- ubiquitin-protein transferase activity
- zinc ion binding
- histone acetyltransferase binding
- androgen receptor binding
Cellular Component
- nucleus
- nucleolus
- cytoplasm
- Golgi apparatus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300747
- Coding exons
- 6
- Length
- 9588
- Individuals with no LoFs
- 125559
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 189
- Defined
- 125748
- p
- 0.000752
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.215 | 288 | 278 | 1.04 | 0.0000160 | 3170 |
| Missense (PolyPhen) | 85 | 85.354 | 0.99586 | 1037 | ||
| Synonymous | -0.367 | 108 | 103 | 1.05 | 0.00000524 | 942 |
| Loss of Function | -0.237 | 27 | 25.7 | 1.05 | 0.00000153 | 262 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.0025 | 0.0025 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00041 | 0.00041 | rare |
| South Asian | 0.0014 | 0.0014 | notable |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a ubiquitin E3 ligase. Acts as a coactivator of androgen receptor (AR) depending on its ubiquitin ligase activity. {ECO:0000269|PubMed:18451177}.;
Intolerance Scores
- LoFtool
- 0.637
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.667
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |