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Gene | MAP2K1 |
Variant | P124L |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 P124L lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P124L confers a gain of function on the Map2k1 protein as demonstrated by Raf-dependent activation of Erk in an in vitro assay and moderately increased Erk and Mek phosphorylation in cultured cells (PMID: 29483135) and confers resistance to some Mek and Braf inhibitors in the context of BRAF V600 mutations in cultured cells (PMID: 19915144). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 P124L |
Transcript | NM_002755.4 |
gDNA | chr15:g.66436825C>T |
cDNA | c.371C>T |
Protein | p.P124L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017022411 | chr15:g.66436825C>T | c.371C>T | p.P124L | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66436825C>T | c.371C>T | p.P124L | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66436825C>T | c.371C>T | p.P124L | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66436825C>T | c.371C>T | p.P124L | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66436825C>T | c.371C>T | p.P124L | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66436825C>T | c.371C>T | p.P124L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 P124L | lymphatic system cancer | predicted - sensitive | Cobimetinib | Case Reports/Case Series | Actionable | In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with mixed histiocytosis harboring MAP2K1 P124L (PMID: 30867592; NCT01953926). | 30867592 |