TRIB2
protein-codingtribbles pseudokinase 2, the group of MicroRNA protein coding host genes
Gene summary
This gene encodes one of three members of the Tribbles family. The Tribbles members share a Trb domain, which is homologous to protein serine-threonine kinases, but lacks the active site lysine and probably lacks a catalytic function. The Tribbles proteins interact and modulate the activity of signal transduction pathways in a number of physiological and pathological processes. This Tribbles member induces apoptosis of cells mainly of the hematopoietic origin. It has been identified as a protein up-regulated by inflammatory stimuli in myeloid (THP-1) cells, and also as an oncogene that inactivates the transcription factor C/EBPalpha (CCAAT/enhancer-binding protein alpha) and causes acute myelogenous leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.8 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 TRIB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021643.4. 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 | 1 | 1 | ||||
| missense | 34 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 35 | 1 | 0 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067675.1 | 3 | MANE Select | |
| Ensembl | ENSP00000155926.4 | 3 | MANE Select | |
| Ensembl | ENSP00000370874.2 | 2 | Standard | |
| Ensembl | ENSP00000384260.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- negative regulation of protein kinase activity
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- regulation of MAP kinase activity
- negative regulation of interleukin-10 biosynthetic process
Molecular Function
- nucleotide binding
- protein kinase activity
- protein kinase inhibitor activity
- transcription factor binding
- mitogen-activated protein kinase kinase binding
Cellular Component
- nucleus
- cytoplasm
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000155926
- Coding exons
- 3
- Length
- 25846
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125714
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.71 | 141 | 211 | 0.669 | 0.0000128 | 2253 |
| Missense (PolyPhen) | 35 | 85.938 | 0.40727 | 883 | ||
| Synonymous | -0.0617 | 93 | 92.2 | 1.01 | 0.00000578 | 692 |
| Loss of Function | 3.27 | 0 | 12.5 | 0.00 | 7.02e-7 | 141 |
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 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interacts with MAPK kinases and regulates activation of MAP kinases. Does not display kinase activity (By similarity). {ECO:0000250|UniProtKB:Q28283, ECO:0000250|UniProtKB:Q96RU8}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.0468
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.834
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |