TAB3

Chr X

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

Also known as: MAP3K7IP3, NAP1

NCBI Gene: 257397 ENSG00000157625 UniProt: Q8N5C8

The encoded protein functions as an adapter in NF-κB and JNK signaling pathways by recognizing specific polyubiquitin chains and linking MAP3K7/TAK1 to TRAF6, facilitating inflammatory signaling cascades. TAB3 variants cause neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (NEDMEBA), which follows autosomal recessive inheritance and presents in early childhood. The gene shows high constraint against loss-of-function variants (LOEUF 0.42), indicating intolerance to such changes in the general population.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429