TRIM33
protein-codingtripartite motif containing 33, the group of Tripartite motif family|Ring finger proteins|Bromodomain containing|PHD finger proteins
Gene summary
The protein encoded by this gene is thought to be a transcriptional corepressor. However, molecules that interact with this protein have not yet been identified. The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~118.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0000158
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRIM33 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015906.4. 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 | 3 | 1 | 4 | 8 | ||
| missense | 80 | 4 | 84 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 87 | 1 | 8 | 96 |
Highest pathogenic variant AF is 0.00003717523
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056990.3 | 20 | MANE Select | |
| Ensembl | ENSP00000351250.2 | 20 | MANE Select | |
| RefSeq | NP_148980.2 | 19 | Standard | |
| Ensembl | ENSP00000358556.2 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| trim33 | Danio rerio | Structure: neutrophil Quality: aggregated abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-Ncore
- Ectoderm Differentiation
- Signal Transduction
- Gene expression (Transcription)
- Generic Transcription Pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- protein ubiquitination
- regulation of transforming growth factor beta receptor signaling pathway
- negative regulation of BMP signaling pathway
- negative regulation of transcription, DNA-templated
Molecular Function
- DNA binding
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
- co-SMAD binding
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358465
- Coding exons
- 20
- Length
- 118383
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125724
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.49 | 259 | 557 | 0.465 | 0.0000280 | 7351 |
| Missense (PolyPhen) | 31 | 160.58 | 0.19306 | 2120 | ||
| Synonymous | -0.810 | 211 | 197 | 1.07 | 0.0000100 | 2158 |
| Loss of Function | 6.74 | 1 | 54.9 | 0.0182 | 0.00000286 | 653 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF- beta/BMP signaling cascade). {ECO:0000250, ECO:0000269|PubMed:10022127, ECO:0000269|PubMed:15820681, ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:19135894}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving TRIM33 is found in papillary thyroid carcinomas (PTCs). Translocation t(1;10)(p13;q11) with RET. The translocation generates the TRIM33/RET (PTC7) oncogene. {ECO:0000269|PubMed:10439047}.;
Recessive Scores
- pRec
- 0.151
Intolerance Scores
- LoFtool
- 0.0280
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |