TRIB1
Tribbles Pseudokinase 1: A Key Regulator of Lipid Metabolism and Myeloid Leukemia
Gene Information Card
| Symbol | TRIB1 |
|---|---|
| Full Name | Tribbles Pseudokinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 8q24.13 |
| NCBI Gene ID | 10221 ncbi.nlm.nih.gov/gene/10221 |
| Ensembl ID | ENSG00000173334 |
| UniProt ID | Q96RU8 |
| OMIM ID | 609461 |
| HGNC ID | 16891 |
| Aliases | C8FW, GIG-2, SKIP1, TRB-1 |
Description
TRIB1 encodes a member of the tribbles family of pseudokinases that function as adaptor proteins regulating signal transduction, protein degradation, and gene expression. TRIB1 modulates MAPK cascades, controls C/EBP transcription factors, and plays critical roles in lipid metabolism, adipogenesis, and hematopoiesis. Dysregulation of TRIB1 is implicated in myeloid leukemias, cardiovascular disease, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia | TRIB1 overexpression blocks C/EBPα-mediated differentiation, promoting leukemogenesis | PMID: 21205788 |
| Chronic Myeloid Leukemia | TRIB1 is a direct target of BCR-ABL1 and contributes to blast crisis | PMID: 23045668 |
| Cardiovascular Disease | TRIB1 variants (e.g., rs2954029) associate with altered lipid profiles and coronary artery disease risk | PMID: 21738478 |
| Familial Combined Hyperlipidemia | TRIB1 locus variants linked to increased triglycerides and LDL cholesterol | PMID: 24097068 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Adipose Tissue | 6.1 | Low |
| Spleen | 5.4 | Low |
| Lung | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (CML) | 18.7 | High expression; BCR-ABL1 dependent |
| HL-60 (AML) | 15.2 | High expression; blocks differentiation |
| HepG2 (Liver) | 9.8 | Moderate; regulates lipid metabolism |
| THP-1 (Monocyte) | 7.1 | Moderate; inflammatory response |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Pro34Leu) | Missense | <0.1% | Unknown functional effect |
| c.457G>A (p.Val153Ile) | Missense | <0.1% | Unknown functional effect |
| rs2954029 | Intergenic variant | Common (MAF ~0.3) | Associated with lipid levels and CAD risk |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in TRIB1.
Gain of Function (GOF)
Overexpression in myeloid leukemias acts as a gain-of-function by inhibiting C/EBPα and promoting proliferation.
Dominant Negative (DN)
Not described for TRIB1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0005515 (protein binding) |
| • GO:0008134 (transcription factor binding) | • GO:0042802 (identical protein binding) |
| • GO:0007254 (JNK cascade) | • GO:0035556 (intracellular signal transduction) |
| • GO:0045944 (positive regulation of transcription by RNA polymerase II) | • GO:0010628 (positive regulation of gene expression) |
| • GO:0048662 (negative regulation of smooth muscle cell proliferation) | • GO:0009749 (response to glucose) |
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Chronic myeloid leukemia (KEGG: hsa05220)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
• Adipocytokine signaling pathway (KEGG: hsa04920)
Protein Summary
TRIB1 is a 372-amino acid pseudokinase that lacks catalytic activity but functions as a scaffold protein. It contains a central pseudokinase domain and C-terminal MAPK-binding motifs. TRIB1 interacts with MAPK kinases (e.g., MEK1) and E3 ubiquitin ligases (e.g., COP1) to target transcription factors such as C/EBPα and C/EBPβ for proteasomal degradation. Through these interactions, TRIB1 regulates myeloid differentiation, lipid metabolism, and inflammatory signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIB1 Knockout HEK293 Cell Line | EDJ-KQ6958 | Human | 10221 | Details Get a Quote |
| TRIB1 Knockout A-549 Cell Line | EDJ-KQ30256 | Human | 10221 | Details Get a Quote |
| TRIB1 Knockout HCT 116 Cell Line | EDJ-KQ31632 | Human | 10221 | Details Get a Quote |
| TRIB1 Knockout HeLa Cell Line | EDJ-KQ31633 | Human | 10221 | Details Get a Quote |
| TRIB1 Knockout HAP1 Cell Line | EDC08048 | Human | 10221 | Details Get a Quote |
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