TNFAIP8L2 Gene (TNF Alpha Induced Protein 8 Like 2)
A key regulator of immune homeostasis and apoptosis, implicated in autoimmune and inflammatory diseases.
Gene Information Card
| Symbol | TNFAIP8L2 |
|---|---|
| Full Name | TNF alpha induced protein 8 like 2 |
| Gene Type | protein coding |
| Chromosomal Location | 1q23.1 |
| NCBI Gene ID | 79627 ncbi.nlm.nih.gov/gene/79627 |
| Ensembl ID | ENSG00000163132 |
| UniProt ID | Q6P589 |
| OMIM ID | 612116 |
| HGNC ID | 28280 |
| Aliases | TIPE2, FLJ23477 |
Description
TNFAIP8L2 (TNF alpha induced protein 8 like 2), also known as TIPE2, is a protein-coding gene located on chromosome 1q23.1. It belongs to the TNFAIP8/TIPE family and is predominantly expressed in immune tissues. TNFAIP8L2 is a critical negative regulator of innate and adaptive immunity, controlling inflammation and maintaining immune homeostasis. It modulates apoptosis and cell survival through NF-κB and JNK signaling pathways. Dysregulation of TNFAIP8L2 has been linked to autoimmune diseases, inflammatory conditions, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | Reduced TNFAIP8L2 expression leads to enhanced immune activation and pro-inflammatory cytokine production, contributing to autoimmunity. | PMID: 21368763; NCBI Gene |
| Inflammatory bowel disease (IBD) | TNFAIP8L2 deficiency in intestinal epithelial cells promotes inflammation and disrupts gut barrier function. | PMID: 25847241; NCBI Gene |
| Sepsis | TNFAIP8L2 downregulation in sepsis patients correlates with excessive inflammatory response and poor prognosis. | PMID: 28652351; NCBI Gene |
| Hepatocellular carcinoma | TNFAIP8L2 expression is downregulated in tumor tissues, leading to increased cell proliferation and metastasis via NF-κB activation. | PMID: 28218245; COSMIC |
| Type 2 diabetes | TNFAIP8L2 expression is reduced in pancreatic islets, contributing to β-cell apoptosis and insulin resistance. | PMID: 26416607; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.4 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Low |
| Lung | 6.5 | Low |
| Liver | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; used in immune studies |
| Jurkat (T cell) | 12.8 | High expression; regulates T cell apoptosis |
| HeLa (cervical) | 4.3 | Low expression; not immune-related |
| A549 (lung) | 2.1 | Low expression; minimal role |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs11117432 | SNV (intronic) | 0.15 (global) | Associated with altered TNFAIP8L2 expression in immune cells; potential risk for autoimmune disease |
| c.485C>T (p.Pro162Leu) | Missense | 0.01 (rare) | May affect protein stability; reported in a lupus patient (ClinVar) |
| c.1-2A>G | Splice site | Not reported | Predicted to disrupt splicing; likely loss-of-function (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., splice site variants) reduce TNFAIP8L2 protein levels, leading to unchecked NF-κB activation and increased inflammation, as observed in autoimmune and inflammatory diseases.
Gain of Function (GOF)
No gain-of-function mutations have been reported; TNFAIP8L2 is primarily a negative regulator, and overexpression is not associated with disease.
Dominant Negative (DN)
Dominant-negative effects are not documented; however, missense mutations in the DED-like domain could theoretically interfere with protein-protein interactions, but evidence is lacking.
View complete mutation data：
Gene Ontology (GO)
| • apoptosis | • immune response |
| • negative regulation of NF-κB transcription factor activity | • negative regulation of JNK cascade |
| • inflammatory response | • regulation of cytokine production |
Pathways
• NF-κB signaling pathway
• JNK signaling pathway
• TNF signaling pathway
• Apoptosis pathway
Protein Summary
TNFAIP8L2 (TIPE2) is a 184-amino acid protein containing a death effector domain (DED)-like domain. It is predominantly expressed in immune cells and acts as a negative regulator of innate and adaptive immunity. TIPE2 inhibits NF-κB and JNK signaling, thereby suppressing inflammatory cytokine production and promoting apoptosis. It also regulates the PI3K/AKT pathway in some contexts. The protein is involved in maintaining immune homeostasis and preventing autoimmunity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFAIP8L2 Knockout HEK293 Cell Line | EDJ-KQ51685 | Human | 79626 | Details Get a Quote |
| TNFAIP8L2-SCNM1 Knockout HEK293 Cell Line | EDJ-KQ52510 | Human | 100534012 | Details Get a Quote |
| TNFAIP8L2 Knockout HeLa Cell Line | EDJ-KQ57195 | Human | 79626 | Details Get a Quote |
| TNFAIP8L2-SCNM1 Knockout HeLa Cell Line | EDJ-KQ60975 | Human | 100534012 | Details Get a Quote |
| TNFAIP8L2 Knockout A-549 Cell Line | EDJ-KQ65704 | Human | 79626 | Details Get a Quote |
| TNFAIP8L2-SCNM1 Knockout A-549 Cell Line | EDJ-KQ69450 | Human | 100534012 | Details Get a Quote |
| TNFAIP8L2 Knockout HCT 116 Cell Line | EDJ-KQ74126 | Human | 79626 | Details Get a Quote |
| TNFAIP8L2-SCNM1 Knockout HCT 116 Cell Line | EDJ-KQ77801 | Human | 100534012 | Details Get a Quote |
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