TRIM27
protein-codingtripartite motif containing 27, the group of Tripartite motif family|Ring finger proteins
Gene summary
This gene encodes 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. This protein localizes to the nuclear matrix. It interacts with the enhancer of polycomb protein and represses gene transcription. It is also thought to be involved in the differentiation of male germ cells. Fusion of the N-terminus of this protein with the truncated C-terminus of the RET gene product has been shown to result in production of the ret transforming protein. [provided by RefSeq, Jul 2008]
- RFP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.0 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 TRIM27 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006510.5. 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 | 36 | 36 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 39 | 0 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006501.1 | 8 | MANE Select | |
| Ensembl | ENSP00000366404.3 | 8 | MANE Select | |
| Ensembl | ENSP00000366399.3 | 9 | Standard | |
| Ensembl | ENSP00000366399.3 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Regulation of PTEN stability and activity
- PTEN Regulation
- PIP3 activates AKT signaling
- Intracellular signaling by second messengers
Biological Process
- negative regulation of transcription by RNA polymerase II
- negative regulation of adaptive immune response
- negative regulation of protein kinase activity
- spermatogenesis
- cell population proliferation
Molecular Function
- nucleic acid binding
- DNA binding
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
Cellular Component
- fibrillar center
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377199
- Coding exons
- 8
- Length
- 20988
- Individuals with no LoFs
- 124823
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 124826
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.70 | 116 | 295 | 0.393 | 0.0000154 | 3362 |
| Missense (PolyPhen) | 17 | 75.329 | 0.22568 | 799 | ||
| Synonymous | -0.173 | 122 | 120 | 1.02 | 0.00000614 | 984 |
| Loss of Function | 4.34 | 2 | 25.8 | 0.0776 | 0.00000120 | 291 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000055 | rare |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of PIK3C2B and inhibits its activity; mediates the formation of 'Lys-48'-linked polyubiquitin chains; the function inhibits CD4 T- cell activation. Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). Has a transcriptional repressor activity by cooperating with EPC1. Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events. May function in male germ cell development. Has DNA-binding activity and preferentially bound to double- stranded DNA. {ECO:0000269|PubMed:10976108, ECO:0000269|PubMed:12807881, ECO:0000269|PubMed:22128329, ECO:0000269|PubMed:23452853}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving TRIM27/RFP is found in papillary thyroid carcinomas (PTCs). Translocation t(6;10)(p21.3;q11.2) with RET. The translocation generates TRIM27/RET and delta TRIM27/RET oncogenes. {ECO:0000269|PubMed:12787916, ECO:0000269|PubMed:3037315}.;
Intolerance Scores
- LoFtool
- 0.112
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.975
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |