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Gene Symbol PTPN11
Synonyms BPTP3 | CFC | JMML | METCDS | NS1 | PTP-1D | PTP2C | SH-PTP2 | SH-PTP3 | SHP2
Gene Description PTPN11, protein tyrosine phosphatase non-receptor type 11, is a member of the PTP Src homology-2 (SH2) domain-containing phosphatases that induces the MAPK signal transduction pathway to regulate growth factor signaling and has been characterized as both an oncogene and tumor suppressor (PMID: 20337577, PMID: 28074573). PTPN11 activating mutations have been identified in a variety of tumors including, lung, colon, brain, thyroid, skin and heme (PMID: 18286234, PMID: 21407260), PTPN11 hypomethylation has been observed in gastric cancer (PMID: 32194661), and germline mutations are implicated in Noonan syndrome (PMID: 28328117, PMID: 32233106).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A461G missense unknown PTPN11 A461G lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). A461G has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
A461T missense loss of function PTPN11 A461T lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). A461T results in decreased Ptpn11 activity and inhibition of Erk activation in cell culture (PMID: 16377799).
A72D missense gain of function - predicted PTPN11 A72D lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). A72D confers a gain of function to the Ptpn11 protein as demonstrated by increased phosphatase activity of Ptpn11 and activation of the MAPK and PI3K signaling pathways (J Clin Oncol 32, 2014 (suppl; abstr e22174)).
A72G missense unknown PTPN11 A72G lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). A72G has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
A72S missense gain of function - predicted PTPN11 A72S lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). A72S is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased substrate dephosphorylation in an in-vitro assay (PMID: 16358218).
A72T missense unknown PTPN11 A72T lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). A72T has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
A72V missense gain of function PTPN11 A72V lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). A72V results in increased substrate dephosphorylation in an in vitro assay (PMID: 16358218), promotes growth factor-independent proliferation, and is associated with resistance to a Shp2 inhibitor in culture (PMID: 29568093). Y
act mut unknown gain of function PTPN11 act mut indicates that this variant results in a gain of function in the Ptpn11 protein. However, the specific amino acid change has not been identified.
D106A missense gain of function - predicted PTPN11 D106A does not lie within any known functional domains of the Ptpn11 protein (UniProt.org). D106A is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased phosphatase activity in an in-vitro phosphatase assay (PMID: 15987685).
D106Y missense unknown PTPN11 D106Y does not lie within any known functional domains of the Ptpn11 protein (UniProt.org). D106Y has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jul 2020).
D146Y missense unknown PTPN11 D146Y lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). D146Y has not been characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
D155Y missense unknown PTPN11 D155Y lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). D155Y has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
D473N missense unknown PTPN11 D473N lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). D473N has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
D61G missense gain of function PTPN11 D61G lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). D61G confers a gain of function to the Ptpn11 protein, as demonstrated by constitutive activation of Ras-Erk signalling (PMID: 18378677), increased cellular adhesion, migration, and invasion in cell culture (PMID: 19008228), and promotes tumor formation in mice (PMID: 26673822).
D61H missense unknown PTPN11 D61H lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). D61H has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
D61N missense unknown PTPN11 D61N lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). D61N leads to increased phosphatase activity, but results in Erk2 activation similar to wild-type Ptpn11 in cell culture (PMID: 15834506), and therefore, its effect on Ptpn11 protein function is unknown.
D61Y missense gain of function PTPN11 D61Y lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). D61Y results in increased activity of protein tyrosine phosphatase (PMID: 15834506), promotes proliferation in culture, and is associated with resistance to a Shp2 inhibitor (PMID: 12717436, PMID: 29568093). Y
dec exp none no effect PTPN11 dec exp indicates decreased expression of the Ptpn11 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
E123D missense unknown PTPN11 E123D lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). E123D has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
E139D missense no effect - predicted PTPN11 E139D lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). E139D has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Ptpn11 (PMID: 29533785).
E139K missense unknown PTPN11 E139K lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). E139K has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
E225D missense unknown PTPN11 E225D does not lie within any known functional domains of the Ptpn11 protein (UniProt.org). E225D has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
E69D missense unknown PTPN11 E69D lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E69D has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
E69K missense unknown PTPN11 E69K lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E69K results in similar cell proliferation and viability levels to wild-type Ptpn11 in once study (PMID: 29533785), but results in increased Ptpn11 phosphatase activity in an in vitro assay (PMID: 15604238) and growth factor-independent proliferation (PMID: 29568093) in other studies, and therefore, its effect on Ptpn11 protein function is unknown.
E76A missense gain of function - predicted PTPN11 E76A lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E76A is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased activity of protein tyrosine phosphatase in cell culture (PMID: 15834506).
E76G missense gain of function PTPN11 E76G lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E76G confers a gain of function to the Ptpn11 protein, as demonstrated by decreased cell adhesion regulation (PMID: 18559669) and loss of the ability to regulate Cdc42 activity (PMID: 26783207).
E76K missense gain of function 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). Y
E76Q missense no effect - predicted PTPN11 E76Q lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E76Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Ptpn11 (PMID: 29533785).
E76V missense gain of function - predicted PTPN11 E76V lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). E76V results in increased Tgfb1-induced expression of the mesenchymal genes Snail1/2, Cdh2, Fn1, Vim, and Col1a1 compared to wild-type Ptpn11 in cultured cells (PMID: 25331952), and therefore, is predicted to lead to a gain of Ptpn11 protein function.
F285L missense unknown PTPN11 F285L lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). F285L has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
F285S missense gain of function PTPN11 F285S lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). F285S confers a gain of function to the Ptpn11 protein as demonstrated by increased basal phosphatase activity and sensitivity to phospholigand stimulation compared to wild-type Ptpn11 in in vitro assays (PMID: 27030275, PMID: 30375388), and increased levels of phosphorylated Erk in cultured cells (PMID: 30375388).
F341Y missense unknown PTPN11 F341Y lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). F341Y has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
F71I missense gain of function - predicted PTPN11 F71I lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). F71I is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased activity of protein tyrosine phosphatase in cell culture (PMID: 15834506).
F71L missense unknown PTPN11 F71L lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). F71L has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
G13D missense unknown PTPN11 G13D lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). G13D has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
G464D missense unknown PTPN11 G464D lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). G464D has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
G503A missense gain of function - predicted PTPN11 G503A lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). G503A, in the context of KMT2A-MLLT10, leads to increased colony size and cell cycle alterations in response to growth factor in culture, macrophage differentiation, and leukemogenesis induction in a shorter time period in mouse models compared to the KMT2A-MLLT10 fusion alone, and individually, results in increased phosphatase activity in an in vitro assay (PMID: 27859216), and therefore, is predicted to lead to a gain of Ptpn11 protein function.
G503E missense unknown PTPN11 G503E lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). G503E has been identified in sequencing studies (PMID: 27276561, PMID: 27486981), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
G503L missense unknown PTPN11 G503L lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). G503L has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
G503R missense unknown PTPN11 G503R lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). G503R has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
G503V missense gain of function - predicted PTPN11 G503V lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). G503V is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased phosphatase activity compared to wild-type Ptpn11 in culture (PMID: 15834506).
G60R missense no effect - predicted PTPN11 G60R lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). G60R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Ptpn11 (PMID: 29533785).
G60V missense unknown PTPN11 G60V lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). G60V has been identified in the scientific literature (PMID: 18701506, PMID: 28972594), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
H114Y missense unknown PTPN11 H114Y lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). H114Y has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
I172T missense unknown PTPN11 I172T lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). I172T has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
I282M missense unknown PTPN11 I282M lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). I282M has been identified in the scientific literature (PMID: 26817465), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
I282V missense gain of function - predicted PTPN11 I282V lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). I282V is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased phosphatase activity in cell culture (PMID: 16358218).
I54T missense unknown PTPN11 I54T lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). I54T has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
inact mut unknown loss of function PTPN11 inact mut indicates that this variant results in a loss of function of the Ptpn11 protein. However, the specific amino acid change has not been identified.
K325T missense unknown PTPN11 K325T lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). K325T has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
K55N missense unknown PTPN11 K55N lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). K55N has not been characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
L117F missense unknown PTPN11 L117F lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). L117F has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
L136H missense unknown PTPN11 L136H lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). L136H has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jun 2020).
L262F missense gain of function PTPN11 L262F lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). L262F results in increased Ptpn11 phosphatase activity and increased phosphorylation of ERK in cell culture (PMID: 28074573).
loss unknown loss of function PTPN11 loss indicates loss of the PTPN11 gene, mRNA, and protein.
M311V missense unknown PTPN11 M311V lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). M311V has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
M504V missense gain of function - predicted PTPN11 M504V lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). M504V is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased phosphatase activity in cell culture (PMID: 16358218).
M82V missense unknown PTPN11 M82V lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). M82V has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
mutant unknown unknown PTPN11 mutant indicates an unspecified mutation in the PTPN11 gene.
N308D missense unknown PTPN11 N308D lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). The functional effect of N308D is conflicting, as it results in similar cell proliferation and viability levels to wild-type Ptpn11 in culture (PMID: 29533785), however, results in increased Ptpn11 phosphatase activity (PMID: 16358218, PMID: 12717436) and enhanced cell proliferation (PMID: 12717436) in other studies.
N339S missense unknown PTPN11 N339S lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). N339S has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jun 2020).
N58K missense no effect - predicted PTPN11 N58K lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). N58K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Ptpn11 (PMID: 29533785).
N58S missense gain of function - predicted PTPN11 N58S lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). N58S has not been biochemically characterized, however, has been characterized as activating in a lung cancer cell line (PMID: 23825065) and is tentatively transforming in cell culture (PMID: 23957426).
N58Y missense unknown PTPN11 N58Y lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). N58Y has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
P491L missense unknown PTPN11 P491L lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). P491L has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
P491Q missense unknown PTPN11 P491Q lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). P491Q has been demonstrated to confer resistance to SHP2 inhibitors in culture (PMID: 30045908), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, May 2020). Y
P491S missense gain of function - predicted PTPN11 P491S lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). P491S results in increased phosphatase activity compared to wild-type Ptpn11 in an in vitro assay (PMID: 24891296), and therefore, is predicted to lead to a gain of Ptpn11 protein function.
Q257L missense unknown PTPN11 Q257L lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). Q257L has been demonstrated to confer resistance to SHP2 inhibitors in combination with T253M in culture (PMID: 30045908), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jul 2020).
Q510E missense loss of function PTPN11 Q510E lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). Q510E results decreased Ptpn11 phosphatase activity and reduced Erk1/2 activation (PMID: 22058153), and leads to decreased differentiation of mature cardiomyocytes, increased Akt and Gsk3b phosphorylation, and elevated nuclear localization of beta-catenin compared to wild-type Ptpn11 in cultured cells (PMID: 21803945).
Q510H missense unknown PTPN11 Q510H lies within the tyrosine-protein phosphatase domain and acts as a substrate binding site (UniProt.org). Q510H has been identified in sequencing studies (PMID: 18925961, PMID: 30325992), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
Q510L missense unknown PTPN11 Q510L lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). Q510L has been identified in sequencing studies (PMID: 27359055, PMID: 28822769, PMID: 28870692), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
Q79R missense unknown PTPN11 Q79R lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). The functional effect of Q79R is conflicting, as it increases protein tyrosine phosphatase activity and induces increased proliferation in cell culture in one study (PMID: 16166557), however in another study, results in similar cell proliferation and viability levels to wild-type Ptpn11 (PMID: 29533785).
R278K missense unknown PTPN11 R278K lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). R278K has not been characterized in the scientific literature and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
R384C missense unknown PTPN11 R384C lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). R384C has not been characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
R498W missense loss of function - predicted PTPN11 R498W lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). R498W demonstrates reduced phosphatase activity compared to wild-type Ptpn11 in an in vitro phosphatase assay (PMID: 24891296) and therefore, is predicted to confer a loss of function on the Ptpn11 protein.
S502A missense unknown PTPN11 S502A lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). S502A has been identified in sequencing studies (PMID: 16358218, PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
S502L missense unknown PTPN11 S502L lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). S502L has been identified in sequencing studies (PMID: 16358218, PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
S502T missense gain of function - predicted PTPN11 S502T lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). S502T results in increased phosphatase activity compared to wild-type Ptpn11 in an in vitro assay (PMID: 15834506), and therefore, is predicted to lead to a gain of Ptpn11 protein function.
T253M missense unknown PTPN11 T253M lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). T253M has been demonstrated to confer resistance to SHP2 inhibitors in combination with Q257L in culture (PMID: 30045908), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jul 2020).
T337M missense unknown PTPN11 T337M lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). T337M has been identified in sequencing studies (PMID: 29636988), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jul 2020).
T468M missense loss of function PTPN11 T468M lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). T468M results in reduced Ptpn11 activity and inhibition of Erk activation in cell culture (PMID: 16377799).
T507K missense gain of function PTPN11 T507K lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). T507K confers a gain of function to the Ptpn11 protein as demonstrated by increased activity of protein tyrosine phosphatase and the ability to transform cells in culture (PMID: 18223690).
T52S missense unknown PTPN11 T52S lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). T52S has been identified in the scientific literature (PMID: 18260110), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
T73I missense unknown PTPN11 T73I lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). The functional effect of T73I is conflicting, as it results in similar cell proliferation and viability levels as wild-type Ptpn11 in one study (PMID: 29533785), however, increases activity of Ptpn11 in cell culture (PMID: 15834506, PMID: 15987685), and demonstrates intermediate transformation ability in another study (PMID: 15710330).
V181I missense unknown PTPN11 V181I lies within the SH2 domain 2 of the Ptpn11 protein (UniProt.org). V181I has been identified in sequencing studies (PMID: 22895193, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Ptpn11 protein function is unknown (PubMed, Jan 2020).
V45L missense gain of function - predicted PTPN11 V45L lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). V45L is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased phosphatase activity in an in vitro phosphatase assay (PMID: 15604238).
V51A missense no effect - predicted PTPN11 V51A lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). V51A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Ptpn11 (PMID: 29533785).
wild-type none no effect Wild-type PTPN11 indicates that no mutation has been detected within the PTPN11 gene.
Y279C missense loss of function PTPN11 Y279C lies within the tyrosine-protein phosphatase domain of the Ptpn11 protein (UniProt.org). Y279C results in decreased Ptpn11 activity, reduced Erk activation in cell culture, and aberrant activation of Akt/mTOR, Jnk and Stat3 in animal models (PMID: 16377799, PMID: 21339643, PMID: 29559584).
Y62C missense gain of function - predicted PTPN11 Y62C lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). Y62C is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased phosphatase activity in an in-vitro phosphatase assay (PMID: 15604238).
Y63C missense gain of function - predicted PTPN11 Y63C lies within the SH2 domain 1 of the Ptpn11 protein (UniProt.org). Y63C is predicted to confer a gain of function to the Ptpn11 protein, as demonstrated by increased Ptpn11 phosphatase activity in cell culture (PMID: 22711529).