MAP3K7

Chr 6AD

mitogen-activated protein kinase kinase kinase 7

Also known as: CSCF, FMD2, MEKK7, TAK1, TGF1a

NCBI Gene: 6885 ENSG00000135341 UniProt: O43318 OMIM: 602614

MAP3K7 encodes a serine/threonine kinase that mediates signal transduction for multiple pathways including TGF-beta, BMP, and cytokine signaling, and serves as a key activator of NF-kappa-B and MAPK pathways in response to environmental stresses. Mutations cause autosomal dominant developmental delay, intellectual disability, and multiple congenital anomalies, often with cardiac defects and distinctive facial features. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.21), reflecting its essential role in cellular signaling pathways.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiospondylocarpofacial syndromeMIM #157800

Frontometaphyseal dysplasia 2MIM #617137

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

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GeneReview available — MAP3K7