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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 |
XM_017022411.2 | 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 |
NM_002755.3 | 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_017022411.3 | 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 |
---|---|---|---|---|---|---|---|
BRAF V600E MAP2K1 I103N | melanoma | resistant | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, overexpression of MAP2K1 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 |
BRAF V600E MAP2K1 I103N | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 26267534). | 26267534 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N was resistant to Zelboraf (vemurafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N was resistant to Tafinlar (dabrafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 I103N | melanoma | resistant | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N was resistant to Braftovi (encorafenib) in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 I103N | melanoma | sensitive | Cobimetinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 I103N | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 36442478). | 36442478 |
BRAF V600E MAP2K1 I103N | melanoma | sensitive | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Braftovi (encorafenib) and Mektovi (binimetinib) synergistically inhibited viability of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 36442478). | 36442478 |