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Gene PTPN11
Variant E76K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions PTPN11 E76K lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E76K confers a gain of function to the Ptpn11 protein as demonstrated by increased protein tyrosine phosphatase activity, Erk1/2 phosphorylation, and migration, invasion, and transformation of cultured cells (PMID: 17942397, PMID: 29568093, PMID: 31807022), and induces increased chromosome instability (PMID: 26755576), promotes tumor formation in mouse models (PMID: 31807022), and is associated with resistance to a Shp2 inhibitor (PMID: 29568093).
Associated Drug Resistance Y

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Transcript NM_002834
gDNA chr12:g.112450406G>A
cDNA c.226G>A
Protein p.E76K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_006719526 chr12:g.112450406G>A c.226G>A p.E76K RefSeq GRCh38/hg38
NM_080601 chr12:g.112450406G>A c.226G>A p.E76K RefSeq GRCh38/hg38
NM_002834 chr12:g.112450406G>A c.226G>A p.E76K RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PTPN11 E76K hematologic cancer sensitive II-B08 Preclinical Actionable In a preclinical study, hematopoietic progenitor cells expressing PTPN11 E76K were sensitive to II-B08, resulting in decreased cell proliferation (PMID: 20170098). 20170098
PTPN11 E76K leukemia sensitive U0126 Preclinical Actionable In a preclinical study, U0126 induced apoptotic activity of leukemia cells expressing PTPN11 E76K in culture (PMID: 17942397). 17942397
PTPN11 E76K leukemia sensitive PD98059 Preclinical Actionable In a preclinical study, PD98059 induced apoptotic activity of leukemia cells expressing PTPN11 E76K in culture (PMID: 17942397). 17942397
PTPN11 E76K myeloid leukemia resistant SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 had no effect on Erk1/2 phosphorylation, Bcl-xl expression, Parp cleavage, and growth of myeloid cells expressing PTPN11 E76K in culture (PMID: 29568093). 29568093
PTPN11 E76K juvenile myelomonocytic leukemia sensitive Cryptotanshinone Preclinical Actionable In a preclinical study, myeloid cells harboring PTPN11 E76K were sensitive to cryptotanshinone in culture, resulting in decreased cell growth (PMID: 23957426). 23957426
BRAF G596R PTPN11 E76K colorectal cancer resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, expression of PTPN11 E76K in colorectal cancer cells harboring BRAF G596R abolished their sensitivity to RMC-4550-induced inhibition of Erk phosphorylation and proliferation in culture (PMID: 30104724). 30104724
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PTPN11 act mut lung non-small cell carcinoma sensitive Refametinib Preclinical Actionable In a preclinical study, Refemetinib (BAY86-9766) inhibited growth of NSCLC cells harboring activating PTPN11 mutations in culture (J Clin Oncol 33, 2015(Suppl; abstr 11077)). detail...
PTPN11 mutant juvenile myelomonocytic leukemia not applicable N/A Clinical Study Emerging In two clinical studies, PTPN11 mutations were frequently identified in patients with juvenile myelomonocytic leukemia and were found to be associated with poor survival (PMID: 19047918, PMID: 21901340), suggesting that this may serve as a future prognostic biomarker. 21901340 19047918
Molecular Profile Protein Effect Treatment Approaches
PTPN11 E76K gain of function SHP2 Inhibitor
BRAF G596R PTPN11 E76K