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Gene | MAP2K1 |
Variant | P124S |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | MAP2K1 P124S lies within the protein kinase domain of the Map2k1 protein (UniProt.org). P124S results in increased Erk1/2 phosphorylation and confers resistance to Mek and Braf inhibitors (PMID: 19915144, PMID: 22197931) and an Egfr antibody (PMID: 33322618) in culture, but has similar induction of cell proliferation and viability levels to wild-type Map2k1 in culture (PMID: 29533785), and therefore, its effect on Map2k1 protein function is unknown. |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 P124S |
Transcript | NM_002755.4 |
gDNA | chr15:g.66436824C>T |
cDNA | c.370C>T |
Protein | p.P124S |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002755.3 | chr15:g.66436824C>T | c.370C>T | p.P124S | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66436824C>T | c.370C>T | p.P124S | RefSeq | GRCh38/hg38 |
XM_017022411 | chr15:g.66436824C>T | c.370C>T | p.P124S | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66436824C>T | c.370C>T | p.P124S | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66436824C>T | c.370C>T | p.P124S | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66436824C>T | c.370C>T | p.P124S | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 P124S | colorectal cancer | predicted - resistant | Cetuximab + Irinotecan | Case Reports/Case Series | Actionable | In a clinical case study, a patient with KRAS/NRAS-wild-type colorectal cancer who progressed on treatment with Erbitux (cetuximab) and Camptosar (irinotecan) was found through ctDNA testing to have acquired MAP2K1 P124S, and preclinical analysis of colorectal cancer cells expressing MAP2K1 P124S demonstrated increased Erk phosphorylation upon treatment with Erbitux (cetuximab) in culture (PMID: 33322618). | 33322618 |