TNFAIP8L3 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TNFAIP8L3 gene, its protein product, expression patterns, and associated diseases.
Gene Information Card
| Symbol | TNFAIP8L3 |
|---|---|
| Full Name | TNF alpha induced protein 8 like 3 |
| Gene Type | protein coding |
| Chromosomal Location | 15q21.2 |
| NCBI Gene ID | 388121 ncbi.nlm.nih.gov/gene/388121 |
| Ensembl ID | ENSG00000178802 |
| UniProt ID | Q5VVP0 |
| OMIM ID | 616348 |
| HGNC ID | 28159 |
| Aliases | TIPE3, FLJ40298 |
Description
TNFAIP8L3 (TNF alpha induced protein 8 like 3) is a protein-coding gene located on chromosome 15q21.2. It belongs to the TNFAIP8/TIPE family, characterized by a conserved DUF759 domain. The encoded protein, TIPE3, is a lipid transfer protein that preferentially binds phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). TIPE3 is involved in regulating cell signaling pathways, including the PI3K/AKT and NF-κB pathways, and has been implicated in cancer progression and immune responses. Its expression is elevated in several cancers, where it promotes tumor growth and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Overexpression of TNFAIP8L3 enhances PI3K/AKT signaling and NF-κB activity, promoting cell proliferation, survival, and metastasis. | Multiple studies (e.g., PMID: 25893246, 28935765) show elevated TIPE3 in lung, breast, and colorectal cancers. |
| Inflammatory diseases | TIPE3 modulates inflammatory responses by regulating NF-κB and MAPK pathways, potentially contributing to chronic inflammation. | Experimental evidence from cell and animal models (PMID: 28935765). |
| Immune disorders | TIPE3 influences T cell activation and cytokine production, affecting immune homeostasis. | Functional studies (PMID: 25893246). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Breast | 8.7 | Low |
| Colon | 15.2 | Medium |
| Liver | 5.1 | Low |
| Kidney | 10.4 | Medium |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung cancer) | 18.5 | High expression |
| MCF7 (Breast cancer) | 12.1 | Moderate |
| HCT116 (Colon cancer) | 20.3 | High |
| HepG2 (Liver cancer) | 6.8 | Low |
| HEK293 (Embryonic kidney) | 9.2 | Moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.Ile41Met) | Missense | 0.01% (gnomAD) | Potential impact on protein stability; functional significance unknown. |
| c.456C>T (p.Ser152Leu) | Missense | 0.005% (gnomAD) | Located in DUF759 domain; may affect lipid binding. |
| c.789_790insA (p.Thr264AsnfsTer5) | Frameshift | Rare | Predicted to cause loss of function due to premature stop codon. |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations leading to premature termination are likely loss-of-function, resulting in truncated protein lacking functional domains.
Gain of Function (GOF)
Missense mutations that increase protein stability or lipid-binding affinity could potentially act as gain-of-function, enhancing oncogenic signaling.
Dominant Negative (DN)
No evidence currently supports dominant-negative effects for TNFAIP8L3 mutations.
View complete mutation data：
Gene Ontology (GO)
| • lipid binding | • phosphatidylinositol binding |
| • phosphatidylinositol-4 | • 5-bisphosphate binding |
| • phosphatidylinositol-3 | • 4 |
| • 5-trisphosphate binding | • signal transduction |
| • negative regulation of apoptotic process | • positive regulation of cell proliferation |
| • positive regulation of NF-κB transcription factor activity | • positive regulation of protein kinase B signaling |
Pathways
• PI3K-Akt signaling pathway
• NF-kappa B signaling pathway
• TNF signaling pathway
Protein Summary
TIPE3 is a 240-amino acid protein with a molecular weight of ~27 kDa. It contains a conserved DUF759 domain that mediates lipid binding. TIPE3 localizes to the plasma membrane and cytoplasm, where it interacts with phosphoinositides to regulate downstream signaling. It promotes cancer cell proliferation and migration by activating AKT and NF-κB pathways. TIPE3 also modulates immune responses by affecting T cell receptor signaling. Its expression is tightly regulated, and dysregulation contributes to tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFAIP8L3 Knockout HEK293 Cell Line | EDJ-KQ15871 | Human | 388121 | Details Get a Quote |
| TNFAIP8L3 Knockout A-549 Cell Line | EDJ-KQ49088 | Human | 388121 | Details Get a Quote |
| TNFAIP8L3 Knockout HCT 116 Cell Line | EDJ-KQ49089 | Human | 388121 | Details Get a Quote |
| TNFAIP8L3 Knockout HeLa Cell Line | EDJ-KQ49090 | Human | 388121 | Details Get a Quote |
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