TNIP3
protein-codingTNFAIP3 interacting protein 3
Gene summary
Enables polyubiquitin modification-dependent protein binding activity. Involved in cellular response to lipopolysaccharide; negative regulation of canonical NF-kappaB signal transduction; and pattern recognition receptor signaling pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~96.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TNIP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024873.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 13 | 1 | 0 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079149.3 | 11 | MANE Select | |
| Ensembl | ENSP00000057513.3 | 11 | MANE Select | |
| RefSeq | NP_001122315.2 | 12 | Standard | |
| RefSeq | NP_001231693.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Rac1-Pak1-p38-MMP-2 pathway
- Post-translational protein modification
- Metabolism of proteins
- Ovarian tumor domain proteases
- Deubiquitination
Biological Process
- MyD88-independent toll-like receptor signaling pathway
- inflammatory response
- protein deubiquitination
- toll-like receptor 4 signaling pathway
- negative regulation of I-kappaB kinase/NF-kappaB signaling
Molecular Function
- protein binding
- polyubiquitin modification-dependent protein binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000509841
- Coding exons
- 13
- Length
- 96059
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125747
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.549 | 176 | 198 | 0.890 | 0.0000102 | 2501 |
| Missense (PolyPhen) | 44 | 55.316 | 0.79543 | 797 | ||
| Synonymous | 0.713 | 65 | 72.7 | 0.894 | 0.00000420 | 610 |
| Loss of Function | 3.24 | 8 | 25.7 | 0.311 | 0.00000125 | 320 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to zinc finger protein TNFAIP3 and inhibits NF- kappa-B activation induced by tumor necrosis factor, Toll-like receptor 4 (TLR4), interleukin-1 and 12-O-tetradecanoylphorbol-13- acetate. Overexpression inhibits NF-kappa-B-dependent gene expression in response to lipopolysaccharide at a level downstream of TRAF6 and upstream of IKBKB. NF-kappa-B inhibition is independent of TNFAIP3 binding. {ECO:0000269|PubMed:17088249}.;
Recessive Scores
- pRec
- 0.150
Intolerance Scores
- LoFtool
- 0.477
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.817
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |