TAB3
protein-codingTGF-beta activated kinase 1 (MAP3K7) binding protein 3, the group of Zinc fingers RANBP2-type
Gene summary
The product of this gene functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. The human genome contains a related pseudogene. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
- MAP3K7IP3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~147.6 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 TAB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152787.5. 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 | 26 | 2 | 2 | 30 | ||
| missense | 98 | 1 | 99 | |||
| nonsense | 6 | 6 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 140 | 3 | 2 | 145 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_690000.3 | 7 | MANE Select | |
| Ensembl | ENSP00000288422.4 | 7 | MANE Select | |
| RefSeq | NP_001386799.1 | 6 | Standard | |
| RefSeq | NP_001386801.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TNF signaling pathway - Homo sapiens (human)
- NOD-like receptor signaling pathway - Homo sapiens (human)
- IL-17 signaling pathway - Homo sapiens (human)
- NF-kappa B signaling pathway - Homo sapiens (human)
- Regulation of toll-like receptor signaling pathway
Biological Process
- activation of MAPK activity
- stimulatory C-type lectin receptor signaling pathway
- MyD88-dependent toll-like receptor signaling pathway
- I-kappaB kinase/NF-kappaB signaling
- JNK cascade
Molecular Function
- protein binding
- metal ion binding
Cellular Component
- cytosol
- plasma membrane
- endosome membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000378933
- Coding exons
- 7
- Length
- 147643
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 5
- Defined
- 125740
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.76 | 189 | 270 | 0.699 | 0.0000201 | 4626 |
| Missense (PolyPhen) | 48 | 95.359 | 0.50336 | 1788 | ||
| Synonymous | 1.28 | 78 | 93.7 | 0.832 | 0.00000691 | 1438 |
| Loss of Function | 3.69 | 5 | 24.9 | 0.201 | 0.00000215 | 360 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000082 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000099 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter linking MAP3K7/TAK1 and TRAF6 or TRAF2. Mediator of MAP3K7 activation, respectively in the IL1 and TNF signaling pathways. Plays a role in activation of NF-kappa-B and AP1 transcription factor. Isoform 2 may be an oncogenic factor. {ECO:0000269|PubMed:14633987, ECO:0000269|PubMed:14766965}.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- LoFtool
- 0.403
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |