TRIB3
tribbles pseudokinase 3
Basic information
Region (hg38): 20:362835-397559
Previous symbols: [ "C20orf97" ]
Links
Phenotypes
GenCC
Source:
- cardiomyopathy (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (73 variants)
- not_provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIB3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021158.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 65 | 74 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 65 | 9 | 2 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TRIB3 | protein_coding | protein_coding | ENST00000217233 | 3 | 16943 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.16e-13 | 0.00325 | 125563 | 0 | 182 | 125745 | 0.000724 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.194 | 238 | 230 | 1.04 | 0.0000167 | 2224 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00252 | 0.00252 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00163 | 0.00147 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000312 | 0.000308 |
| Middle Eastern | 0.00163 | 0.00147 |
| South Asian | 0.00242 | 0.00242 |
| Other | 0.000982 | 0.000652 |
dbNSFP
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}.;
- Pathway
- 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;Signal Transduction;VEGFA-VEGFR2 Pathway;Activation of AKT2;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;PI3K Cascade;Costimulation by the CD28 family;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Immune System;Adaptive Immune System;PIP3 activates AKT signaling;Negative regulation of the PI3K/AKT network;Signaling by VEGF;IRS-related events triggered by IGF1R;IGF1R signaling cascade;TNFalpha;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);VEGFR2 mediated vascular permeability
(Consensus)
Recessive Scores
- pRec
- 0.0920
Intolerance Scores
- loftool
- 0.956
- rvis_EVS
- 0.47
- rvis_percentile_EVS
- 78.8
Haploinsufficiency Scores
- pHI
- 0.120
- hipred
- N
- hipred_score
- 0.398
- ghis
- 0.383
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Trib3
- Phenotype
- cellular phenotype; endocrine/exocrine gland phenotype; hematopoietic system phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- trib3
- Affected structure
- determination of liver left/right asymmetry
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- 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;positive regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;cellular response to insulin stimulus;response to endoplasmic reticulum stress;regulation of MAP kinase activity;negative regulation of fat cell differentiation;negative regulation of fatty acid biosynthetic process;negative regulation of transcription, DNA-templated;positive regulation of ubiquitin-protein transferase activity;negative regulation of protein kinase B signaling;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- Cellular component
- nucleus;cytosol;plasma membrane
- Molecular function
- transcription corepressor activity;protein kinase inhibitor activity;protein binding;ATP binding;kinase activity;protein kinase binding;mitogen-activated protein kinase kinase binding;ubiquitin protein ligase binding;ubiquitin-protein transferase regulator activity