TRIB3
protein-codingtribbles pseudokinase 3
Gene summary
The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. Differential promoter usage and alternate splicing result in multiple transcript variants. [provided by RefSeq, Jul 2014]
- C20orf97
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0004994
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRIB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021158.5. 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 | 2 | 2 | ||||
| missense | 74 | 9 | 83 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 76 | 9 | 2 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066981.2 | 3 | MANE Select | |
| Ensembl | ENSP00000217233.3 | 3 | MANE Select | |
| RefSeq | NP_001288117.1 | 3 | Standard | |
| RefSeq | NP_001288119.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| trib3 | Danio rerio | Structure: determination of liver left/right asymmetry Quality: disrupted abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Insulin resistance - Homo sapiens (human)
- Adipogenesis
- Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
- Photodynamic therapy-induced unfolded protein response
- Insulin Signaling
Biological Process
- negative regulation of transcription by RNA polymerase II
- protein phosphorylation
- negative regulation of protein kinase activity
- regulation of glucose transmembrane transport
- regulation of lipid metabolic process
Molecular Function
- transcription corepressor activity
- protein kinase inhibitor activity
- protein binding
- ATP binding
- kinase activity
Cellular Component
- nucleus
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000217233
- Coding exons
- 3
- Length
- 16943
- Individuals with no LoFs
- 125563
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 182
- Defined
- 125745
- p
- 0.000724
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.194 | 238 | 230 | 1.04 | 0.0000167 | 2224 |
| Missense (PolyPhen) | 82 | 90.189 | 0.9092 | 939 | ||
| Synonymous | 0.181 | 102 | 104 | 0.977 | 0.00000736 | 834 |
| Loss of Function | -1.28 | 17 | 12.2 | 1.40 | 8.60e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0024 | 0.0024 | notable |
| Latino/Admixed American | 0.00012 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0016 | 0.0015 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00031 | 0.00031 | rare |
| South Asian | 0.0024 | 0.0024 | notable |
| Other | 0.00098 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. Binds to ATF4 and inhibits its transcriptional activation activity. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. Does not display kinase activity. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. Can inhibit APOBEC3A editing of nuclear DNA. {ECO:0000269|PubMed:12736262, ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:15781252, ECO:0000269|PubMed:22977230}.;
Recessive Scores
- pRec
- 0.0920
Intolerance Scores
- LoFtool
- 0.956
- RVIS EVS
- 0.47
- RVIS percentile EVS
- 78.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |