MAPK1
Chr 22ADmitogen-activated protein kinase 1
Also known as: ERK, ERK-2, ERK2, ERT1, MAPK2, NS13, P42MAPK, PRKM1
The MAPK1 protein is a serine/threonine kinase that serves as an essential component of the MAP kinase/ERK signaling pathway, regulating cellular processes including proliferation, differentiation, transcription, and development through phosphorylation of diverse nuclear and cytoplasmic substrates. Mutations cause autosomal dominant Noonan syndrome 13, a developmental disorder affecting multiple organ systems. This gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.175), indicating that complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MAPK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery
ACTIVE NOT RECRUITINGRASopathy Biorepository
RECRUITINGExternal Resources
Links to major genomics databases and tools