TNIP1 Gene: Function, Disease Associations, and Clinical Significance
TNIP1 encodes A20-binding protein ABIN-1, a key regulator of NF-κB signaling, implicated in autoimmune and inflammatory diseases.
Gene Information Card
| Symbol | TNIP1 |
|---|---|
| Full Name | TNFAIP3 interacting protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q33.1 |
| NCBI Gene ID | 10318 ncbi.nlm.nih.gov/gene/10318 |
| Ensembl ID | ENSG00000145860 |
| UniProt ID | Q15025 |
| OMIM ID | 607714 |
| HGNC ID | 16955 |
| Aliases | ABIN-1, NAF1, VAN |
Description
TNIP1 (TNFAIP3 interacting protein 1) encodes ABIN-1, a ubiquitin-binding protein that negatively regulates NF-κB signaling. It interacts with TNFAIP3 (A20) and other proteins to modulate inflammatory responses. TNIP1 is involved in multiple cellular processes including apoptosis, autophagy, and innate immunity. Genetic variants in TNIP1 are associated with several autoimmune and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Psoriasis | TNIP1 variants reduce ABIN-1 expression, leading to enhanced NF-κB activity and increased inflammatory cytokine production in keratinocytes. | GWAS and functional studies (e.g., Nair et al., 2009; Tsoi et al., 2012) |
| Systemic lupus erythematosus (SLE) | TNIP1 risk alleles impair ABIN-1 function, promoting aberrant immune activation and autoantibody production. | GWAS (Gateva et al., 2009; Han et al., 2009) |
| Systemic sclerosis | TNIP1 polymorphisms are associated with disease susceptibility, possibly via dysregulated NF-κB signaling in fibroblasts. | GWAS (Radstake et al., 2010) |
| Chronic inflammatory diseases | TNIP1 variants may contribute to inflammation in conditions like rheumatoid arthritis and inflammatory bowel disease. | Candidate gene studies (e.g., Orozco et al., 2009) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 20.1 | Medium |
| Spleen | 18.5 | Medium |
| Lung | 12.3 | Low |
| Liver | 8.7 | Low |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.4 | Cervical carcinoma; high expression |
| K562 | 18.2 | Leukemia; moderate expression |
| MCF7 | 15.6 | Breast carcinoma; moderate expression |
| HepG2 | 12.1 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs17728338 | SNP (intronic) | ~0.15 (minor allele frequency) | Associated with psoriasis and SLE; reduces TNIP1 expression |
| rs10036748 | SNP (intronic) | ~0.20 | Associated with SLE; affects splicing or regulatory elements |
| rs4958881 | SNP (intronic) | ~0.10 | Associated with systemic sclerosis |
| Missense variants (e.g., p.Arg114Trp) | Missense | Rare | May impair ABIN-1 ubiquitin-binding or NF-κB inhibition |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TNIP1 reduce ABIN-1 expression or disrupt its ubiquitin-binding domain, leading to increased NF-κB activity and pro-inflammatory cytokine production. This is the primary mechanism for disease-associated variants.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for TNIP1. Most variants are loss-of-function or hypomorphic.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by interfering with ABIN-1 oligomerization or interaction with A20, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • ubiquitin binding |
| • NF-kappaB binding | • signal transduction |
| • negative regulation of NF-kappaB transcription factor activity | • inflammatory response |
| • apoptotic process | • autophagy |
Pathways
• NF-kappaB signaling pathway
• TNF signaling pathway
• Toll-like receptor signaling pathway
• IL-1 signaling pathway
• A20-mediated deubiquitination pathway
Protein Summary
ABIN-1 (A20-binding inhibitor of NF-κB activation) is a 648-amino acid protein containing a ubiquitin-binding domain (UBAN) and a NEMO-binding domain. It interacts with polyubiquitinated proteins and TNFAIP3 (A20) to inhibit NF-κB signaling. ABIN-1 also regulates apoptosis and autophagy. Its expression is ubiquitous, with higher levels in immune tissues. Post-translational modifications include phosphorylation and ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNIP1 Knockout HEK293 Cell Line | EDJ-KQ1948 | Human | 10318 | Details Get a Quote |
| TNIP1 Knockout A-549 Cell Line | EDJ-KQ21890 | Human | 10318 | Details Get a Quote |
| TNIP1 Knockout HCT 116 Cell Line | EDJ-KQ21891 | Human | 10318 | Details Get a Quote |
| TNIP1 Knockout HeLa Cell Line | EDJ-KQ21892 | Human | 10318 | Details Get a Quote |
