MAP3K8

Chr 10

mitogen-activated protein kinase kinase kinase 8

Also known as: AURA2, COT, EST, ESTF, MEKK8, TPL2, Tpl-2, c-COT

NCBI Gene: 1326 ENSG00000107968 UniProt: P41279

MAP3K8 encodes a serine/threonine protein kinase that activates MAPK/ERK and JNK signaling pathways and is required for TLR4-mediated inflammatory responses, T-helper cell differentiation, and cytokine production including TNF-alpha and interleukin-8. The gene is highly constrained against loss-of-function variants, but no Mendelian pediatric disorders have been definitively associated with germline MAP3K8 mutations. Somatic mutations in this gene contribute to lung cancer development.

ResearchSummary from RefSeq, OMIM, UniProt

This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

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)

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P/LP submissions

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P/LP missense

0.32

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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