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Gene | MAP2K1 |
Variant | I103N |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | MAP2K1 I103N lies within the protein kinase domain of the Map2k1 protein (UniProt.org). I103N confers a gain of function to the Map2k1 protein as demonstrated by elevated basal kinase activity in an in vitro assay (PMID: 12370306), increased Map2k1 autophosphorylation (PMID: 29753091), and transformation activity in cell culture and increased proliferation in a competition assay (PMID: 36442478), and is also associated with resistance to Mek inhibitors (PMID: 12370306, PMID: 19915144). |
Associated Drug Resistance | Y |
Category Variants Paths |
MAP2K1 mutant MAP2K1 act mut MAP2K1 I103N |
Transcript | NM_002755.4 |
gDNA | chr15:g.66436762T>A |
cDNA | c.308T>A |
Protein | p.I103N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017022411 | chr15:g.66436762T>A | c.308T>A | p.I103N | RefSeq | GRCh38/hg38 |
NM_002755.3 | chr15:g.66436762T>A | c.308T>A | p.I103N | RefSeq | GRCh38/hg38 |
NM_002755 | chr15:g.66436762T>A | c.308T>A | p.I103N | RefSeq | GRCh38/hg38 |
XM_017022411.3 | chr15:g.66436762T>A | c.308T>A | p.I103N | RefSeq | GRCh38/hg38 |
NM_002755.4 | chr15:g.66436762T>A | c.308T>A | p.I103N | RefSeq | GRCh38/hg38 |
XM_017022411.2 | chr15:g.66436762T>A | c.308T>A | p.I103N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
MAP2K1 I103N | Advanced Solid Tumor | decreased response | CI-1040 | Preclinical - Biochemical | Actionable | In a preclinical study, MAP2K1 I103N demonstrated decreased sensitivity to CI-1040 (PD184352) in an in vitro kinase assay (PMID: 12370306). | 12370306 |
MAP2K1 I103N | Advanced Solid Tumor | predicted - sensitive | SCH772984 | Preclinical - Biochemical | Actionable | In a preclinical study, SCH772984 inhibited downstream signaling in transformed cells expressing MAP2K1 I103N in culture (PMID: 32641410). | 32641410 |