TAB3

Chr X

TGF-beta activated kinase 1 (MAP3K7) binding protein 3

Also known as: MAP3K7IP3, NAP1

NCBI Gene: 257397ENSG00000157625UniProt: Q8N5C8

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]

130
ClinVar variants
71
Pathogenic / LP
0.62
pLI score
0
Active trials
Clinical Summary— TAB3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 56 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.42LOEUF
pLI 0.617
Z-score 3.69
OE 0.20 (0.10–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.76Z-score
OE missense 0.70 (0.62–0.79)
189 obs / 270.4 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.0.20 (0.10–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.62–0.79)
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.0.83
0≤1.21.6
LoF obs/exp: 5 / 24.9Missense obs/exp: 189 / 270.4Syn Z: 1.28

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic1
VUS56
Likely Benign2
Benign1
70
Pathogenic
1
Likely Pathogenic
56
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
70
0
70
Likely Pathogenic
0
0
1
0
1
VUS
0
48
8
0
56
Likely Benign
0
0
0
2
2
Benign
0
0
1
0
1
Total048802130

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

View in ClinVar →

Protein Context — Lollipop Plot

TAB3 · 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
TAB3 promotes human esophageal squamous cell carcinoma proliferation and invasion via the NF‑κB pathway.
Zhao J et al.·Oncol Rep
2018
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.
Chen W et al.·Cardiovasc Diabetol
2024Review
The deubiquitinase OTUD4 suppresses TAK1 kinase-dependent NF-κB signaling and inflammation.
Liu Z et al.·J Biol Chem
2025
miR‑27a‑3p upregulation by p65 facilitates cervical tumorigenesis by increasing TAB3 expression and is involved in the positive feedback loop of NF‑κB signaling.
Li M et al.·Oncol Rep
2023
TAB3 overexpression promotes cell proliferation in non-small cell lung cancer and mediates chemoresistance to CDDP in A549 cells via the NF-κB pathway.
Chen J et al.·Tumour Biol
2016
MicroRNA-26b suppresses the NF-κB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3.
Zhao N et al.·Mol Cancer
2014
Hsa-microRNA-27b-3p inhibits hepatocellular carcinoma progression by inactivating transforming growth factor-activated kinase-binding protein 3/nuclear factor kappa B signalling.
Wen J et al.·Cell Mol Biol Lett
2022
Intra-familial phenotype variant in hypoplastic amelogenesis imperfecta under a complex genetic component: a family report, whole-exome sequencing, and literature review.
Lanza CRM et al.·J Appl Oral Sci
2025Review
Autophagy suppression facilitates macrophage M2 polarization via increased instability of NF-κB pathway in hepatocellular carcinoma.
Gao Z et al.·Int Immunopharmacol
2023
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