protein
Dual specificity mitogen-activated protein kinase kinase 2
aka MAP kinase kinase 2, MAPKK 2
Gene
MAP2K2
Organism
Homo sapiens(9606)
Length
400 aa
Mass
44,424 Da
MAP2K2 encodes dual specificity mitogen-activated protein kinase kinase 2, a 400-amino acid serine/threonine kinase that phosphorylates both threonine and tyrosine residues within the Thr-Glu-Tyr motif of MAP kinases. The protein activates ERK1 and ERK2 and also regulates BRAF kinase activity through a KSR1/KSR2-dependent mechanism by relieving intramolecular inhibitory interactions (UniProt: P36507).
MAP2K2 functions within the MAPK/ERK signaling cascade, a critical pathway for cellular proliferation and differentiation. Mutations in MAP2K2 cause cardiofaciocutaneous syndrome 4 (CFC4), a congenital disorder characterized by distinctive facial features, cardiac malformations including pulmonic stenosis and hypertrophic cardiomyopathy, and intellectual disability, along with ectodermal abnormalities such as sparse hair and keratotic skin lesions (UniProt: P36507).
MAP2K2 is classified as syndromic autism-associated (SFARI Cat: S), reflecting its documented link to autism spectrum disorder within syndromic presentations. The intellectual disability component of CFC4 and the known role of MAPK signaling in neurodevelopment suggest a mechanistic connection to neurodevelopmental phenotypes.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126)
Disease associations
Cardiofaciocutaneous syndrome 4CFC4
A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices.
Sources
Last updated 5/6/2026, 5:24:43 AM