Dual specificity mitogen-activated protein kinase kinase 1

MAP2K1 encodes dual specificity mitogen-activated protein kinase kinase 1, a 393-amino acid protein kinase essential to the MAPK/ERK signal transduction cascade (UniProt: Q02750). It phosphorylates both threonine and tyrosine residues on extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, propagating signals initiated by growth factors, cytokines, and hormones. The pathway regulates diverse cellular processes including growth, survival, differentiation, and cytoskeletal rearrangement through effects on transcription, metabolism, and organellar dynamics.

Mutations in MAP2K1 are associated with cardiofaciocutaneous syndrome 3 (CFC3), a multiple congenital anomaly disorder characterized by distinctive facial features, congenital heart defects, and intellectual disability, alongside ectodermal abnormalities (UniProt: Q02750). The gene has also been linked to melorheostosis, a sclerosing bone disorder causing hyperostosis of long bones.

MAP2K1 carries SFARI classification as syndromic (SFARI Cat S), indicating curated evidence for association with autism spectrum disorder in a syndromic context, likely through the intellectual disability and developmental features accompanying cardiofaciocutaneous syndrome.