TAB1

Chr 22

TGF-beta activated kinase 1 (MAP3K7) binding protein 1

Also known as: 3'-Tab1, MAP3K7IP1

NCBI Gene: 10454ENSG00000100324UniProt: Q15750

The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such as those induced by TGF beta, interleukin 1, and WNT-1. This protein interacts and thus activates TAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents an alternative activation pathway, in addition to the MAPKK pathways, which contributes to the biological responses of MAPK14 to various stimuli. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

102
ClinVar variants
14
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TAB1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 73 VUS of 102 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.000
Z-score 1.81
OE 0.60 (0.39–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.75Z-score
OE missense 0.73 (0.66–0.81)
239 obs / 328.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.39–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.66–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 14 / 23.5Missense obs/exp: 239 / 328.1Syn Z: 0.25

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS73
Likely Benign2
Benign2
14
Pathogenic
73
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
69
4
0
73
Likely Benign
0
1
0
1
2
Benign
0
0
1
1
2
Total07019291

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TAB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma.
Yuan L et al.·Cell Death Differ
2022
Identification of novel therapeutic targets for cognitive performance and associations with brain health.
Zhang LY et al.·Transl Psychiatry
2025
Chlamydia trachomatis antigen induces TLR4-TAB1-mediated inflammation, but not cell death, in maternal decidua cells.
Ortiz B et al.·Am J Reprod Immunol
2023
The deubiquitinase OTUD4 suppresses TAK1 kinase-dependent NF-κB signaling and inflammation.
Liu Z et al.·J Biol Chem
2025
Senescent CD4(+) T cells and autoimmune diseases: mechanisms and therapeutic prospects.
Hu Y et al.·Autoimmun Rev
2026Review
Palmatine alleviates LPS-induced acute lung injury via interfering the interaction of TAK1 and TAB1.
Song Y et al.·Biochem Pharmacol
2022
Expression of TAK1/TAB1 expression in non-small cell lung carcinoma and adjacent normal tissues and their clinical significance.
Zhu J et al.·Int J Clin Exp Pathol
2015
Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia.
Sonowal H et al.·Cancer Res Commun
2025Clinical trial
Dual-target MDM2/MDMX inhibitor increases the sensitization of doxorubicin and inhibits migration and invasion abilities of triple-negative breast cancer cells through activation of TAB1/TAK1/p38 MAPK pathway.
Fan Y et al.·Cancer Biol Ther
2019
The interaction of TAK1 and TAB1 enhances LPS-induced cytokine release via modulating NF-κB activation (Larimichthys crocea).
Bao SY et al.·Fish Shellfish Immunol
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools