Gene Detail

Gene Symbol SRC
Synonyms ASV | c-SRC | p60-Src | SRC1 | THC6
Gene Description SRC, SRC proto-oncogene, non-receptor tyrosine kinase, is a member of mutliple signaling pathways, playing a role in a variety of cellular processes including proliferation, differentiation, survival, motility, and angiogenesis (PMID: 19581523). Activation and/or overexpression of SRC has been observed in many cancers (PMID: 24788409), and SRC activating mutations, although rare, have been identified in colon cancer (PMID: 9988270, PMID: 19581523).
Entrez Id 6714
Chromosome 20
Map Location 20q11.23
Canonical Transcript NM_198291

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
P171Q missense unknown SRC P171Q lies within the SH2 domain of the Src protein (UniProt.org). P171Q has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
A91V missense unknown SRC A91V lies within the SH3 domain of the Src protein (UniProt.org). A91V has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
Q256fs frameshift loss of function - predicted SRC Q256fs results in a change in the amino acid sequence of the Src protein beginning at aa 256 of 536, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of protein kinase domain (UniProt.org), Q256fs is predicted to lead to a loss of Src protein function.
over exp unknown no effect SRC over exp indicates an over expression of the Src protein. However, the mechanism causing the over expression is not specified.
T341M missense gain of function SRC T341M lies within the protein kinase domain of the Src protein (UniProt.org). T341M results in increased Src autophosphorylation and substrated phosphorylation, increased cell survival in culture (PMID: 18794843), and acquired resistance to dasatinib (PMID: 27222538). Y
W121R missense unknown SRC W121R lies within the SH3 domain of the Src protein (UniProt.org). W121R has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
T341I missense gain of function SRC T341I lies within the protein kinase domain of the Src protein (UniProt.org). T341I results in increased Src autophosphorylation and substrated phosphorylation, and increased cell survival in culture (PMID: 18794843).
wild-type none no effect Wild-type SRC indicates that no mutation has been detected within the Src gene.
C501R missense unknown SRC C501R lies within the protein kinase domain of the Src protein (UniProt.org). C501R has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
D407H missense unknown SRC D407H lies within the protein kinase domain of the Src protein (UniProt.org). D407H has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
I113F missense unknown SRC I113F lies within the SH3 domain of the Src protein (UniProt.org). I113F has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
D389E missense unknown SRC D389E lies within the protein kinase domain of the Src protein (UniProt.org). D389E has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
P171R missense unknown SRC P171R lies within the SH2 domain of the Src protein (UniProt.org). P171R has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
act mut unknown gain of function SRC act mut indicates that this variant results in a gain of function in the Src protein. However, the specific amino acid change has not been identified.
S269L missense unknown SRC S269L does not lie within any known functional domains of the Src protein (UniProt.org). S269L has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
G347E missense unknown SRC G347E lies within the protein kinase domain of the Src protein (UniProt.org). G347E has been identified in sequencing studies (PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
E342K missense unknown SRC E342K lies within the protein kinase domain of the Src protein (UniProt.org). E342K has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
R220S missense unknown SRC R220S lies within the SH2 domain of the Src protein (UniProt.org). R220S has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
E527K missense gain of function SRC E527K does not lie within any known functional domains of the Src protein (UniProt.org). E527K results in resistance of Src to phosphorylation and inactivation by CSK, increased Src kinase activity and phosphorylation in culture, leading to blood and bone pathologies in animal models (PMID: 7592628, PMID: 26936507), and is associated with drug resistance in culture (PMID: 25350844). Y
S225I missense unknown SRC S225I lies within the SH2 domain of the Src protein (UniProt.org). S225I has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
amp none no effect SRC amplification indicates an increased number of copies of the SRC gene. However, the mechanism causing the increase is unspecified.
V140M missense unknown SRC V140M lies within the SH3 domain of the Src protein (UniProt.org). V140M has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
mutant unknown unknown SRC mutant indicates an unspecified mutation in the SRC gene.
K298E missense unknown SRC K298E lies within the protein kinase domain of the Src protein (UniProt.org). K298E has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
D351N missense unknown SRC D351N lies within the protein kinase domain of the Src protein (UniProt.org). D351N has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
positive unknown no effect SRC positive indicates the presence of the SRC gene, mRNA, and/or protein.
T183M missense unknown SRC T183M lies within the SH2 domain of the Src protein (UniProt.org). T183M has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
Y530* nonsense unknown SRC Y530* results in a premature truncation of the Src protein at amino acid 530 of 536 (UniProt.org). Y530* has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
G133C missense unknown SRC G133C lies within the SH3 domain of the Src protein (UniProt.org). G133C has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
W121C missense unknown SRC W121C lies within the SH3 domain of the Src protein (UniProt.org). W121C has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
P136S missense unknown SRC P136S lies within the SH3 domain of the Src protein (UniProt.org). P136S has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
R483W missense unknown SRC R483W lies within the protein kinase domain of the Src protein (UniProt.org). R483W has been identified in the scientific literature (PMID: 30004690), but has not been biochemically characterized and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
R163W missense unknown SRC R163W lies within the SH2 domain of the Src protein (UniProt.org). R163W has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
Q531* nonsense gain of function SRC Q531* results in a premature truncation of the Src protein at amino acid 531 of 536 (UniProt.org). Q531* confers a gain of function on the Src protein as demonstrated by increased Src kinase activity compared to wild-type Src, transformation of cultured cells, increased cell invasion, and tumor metastasis in animal models (PMID: 9988270).
P428S missense unknown SRC P428S lies within the protein kinase domain of the Src protein (UniProt.org). P428S has been identified in the scientific literature (PMID: 30004690), but has not been biochemically characterized and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
P506L missense unknown SRC P506L lies within the protein kinase domain of the Src protein (UniProt.org). P506L has not been characterized in the scientific literature and therefore, its effect on Src protein function is unknown (PubMed, Nov 2018).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SRC over exp clear cell renal cell carcinoma no benefit Cediranib + Saracatinib Phase II Actionable In a Phase II clinical trial, baseline expression of SRC was not predictive for response to Saracatinib (AZD0530) and Recentin (cediranib) relative to Recentin (cediranib) in patients with metastatic clear-cell renal cell carcinoma (PMID: 26802156). 26802156
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Dasatinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Selumetinib (AZD6244) synergistically inhibited proliferation and induced apoptosis in thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer resistant Dasatinib Preclinical - Cell line xenograft Actionable In a preclinical study, thyroid cancer cell lines harboring HRAS G13R and KRAS G12R with an acquired SRC T341M mutation demonstrated resistance to Sprycel (dasatinib) in culture and in cell line xenograft models (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Dasatinib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited proliferation and induced apoptosis in thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture, and resulted in sustained tumor suppression and prolonged survival in cell line xenograft models (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of Sprycel (dasatinib)-resistant thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of Sprycel (dasatinib)-resistant thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M in culture and in cell line xenograft models (PMID: 27222538). 27222538
IDH1 R132C SRC T341I intrahepatic cholangiocarcinoma resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S acquired resistance to Sprycel (dasatinib) after over expressing SRC T341I in culture (PMID: 27231123). 27231123
ERBB2 amp SRC E527K gastroesophageal junction adenocarcinoma resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, an ERBB2 (HER2)-amplified gastroesophageal cancer cell line initially sensitive to treatment with Tykerb (lapatinib) in culture developed resistance and was subsequently found to have acquired a secondary drug resistant mutation, SRC E527K (PMID: 25350844). 25350844
ERBB2 amp SRC E527K gastroesophageal junction adenocarcinoma sensitive Lapatinib + Saracatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Tykerb (lapatinib) and Saracatinib (AZD0530) inhibited growth of ERBB2 (HER2)-amplified gastroesophageal adenocarcinoma cells harboring SRC E527K in culture (PMID: 25350844). 25350844
SRC amp non-small cell lung carcinoma sensitive Derazantinib Phase I Actionable In a Phase I trial, ARQ 087 treatment resulted in 25% tumor reduction and stable disease for 36 weeks in a squamous non-small cell lung carcinoma patient harboring SRC amplification (PMID: 28972963; NCT01752920). 28972963 detail...
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of SRC, ERBB2 (HER2), STK11, and NOTCH1 (PMID: 29636358). 29636358
ALK rearrange SRC pos non-small cell lung carcinoma sensitive Saracatinib + Ceritinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Saracatinib (AZD0530) and Zykadia (ceritinib) demonstrated efficacy in non-small cell lung cancer patient derived cells harboring an ALK fusion and upregulation of SRC in culture (PMID: 25394791). 25394791
EML4-ALK SRC pos lung cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines harboring EML4-ALK and elevated Src activity were resistant to Xalkori (crizotinib) induced growth inhibition in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4-ALK SRC pos Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines harboring EML4-ALK and elevated Src activity were resistant to Zykadia (ceritinib) induced growth inhibition in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4-ALK SRC pos lung cancer sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, TPX-0005 inhibited Alk and Src signaling, and cell proliferation in lung cancer cell lines harboring EML4-ALK and elevated Src activity in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
SRC positive glioblastoma multiforme sensitive Si306 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, Si306 in combination with radiotherapy decreased growth of radiotherapy-sensitive SRC-positive glioblastoma cells in culture and decreased tumor growth in cell line xenograft models, with increased efficacy compared to Si306 or radiotherapy alone (PMID: 27196762). 27196762
SRC positive glioblastoma multiforme sensitive Si306 Preclinical - Cell line xenograft Actionable In a preclinical study, Si306 inhibited SRC phosphorylation and proliferation of SRC-expressing glioblastoma cell lines in culture, and inhibited tumor growth and increased survival in cell line xenograft models (PMID: 27196762). 27196762
SRC positive biliary tract cancer sensitive Bosutinib + Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, Bosulif (bosutinib) and Platinol (cisplatin) synergistically inhibited Src signaling, decreased proliferation and migration of billary tract cancer cell lines in culture, and inhibited tumor growth in cell line xenograft models (PMID: 27196758). 27196758
SRC positive triple-receptor negative breast cancer sensitive KX2-391 Preclinical - Cell line xenograft Actionable In a preclinical study, KX2-392 inhibited Src signaling and proliferation in triple-receptor negative breast cancer cell lines in culture, and suppressed tumor growth in xenograft models (PMID: 22784709). 22784709
SRC positive Advanced Solid Tumor predicted - sensitive Bosutinib Preclinical - Cell culture Actionable In a preclinical study, Bosulif (bosutinib) inhibited invasion and migration of Src-positive cells in culture (PMID: 18483306). 18483306
SRC positive triple-receptor negative breast cancer sensitive BIRB-796 + Dasatinib Preclinical - Cell culture Actionable In a preclinical study, BIRB-796 in combination with Sprycel (dasatinib) resulted in improved growth inhibition in both 2D and 3D cultures of triple-receptor negative breast cancer cell lines with elevated Src activity compared to single agent treatment (PMID: 27154914). 27154914
SRC positive glioblastoma multiforme sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) treatment resulted in a strong antitumoral effect in GBM cell lines with high levels of Src phosphorylation (PMID: 19098899). 19098899
SRC positive biliary tract cancer sensitive Bosutinib + Gemcitabine Preclinical - Cell line xenograft Actionable In a preclinical study, Bosulif (bosutinib) and Gemzar (gemcitabine) synergistically inhibited Src signaling, decreased proliferation and migration of billary tract cancer cell lines in culture, and inhibited tumor growth in cell line xenograft models (PMID: 27196758). 27196758
SRC positive biliary tract cancer sensitive Bosutinib Preclinical - Cell line xenograft Actionable In a preclinical study, Bosulif (bosutinib) inhibited Src signaling, resulted in cell cycle arrest and decreased invasion of biliary tract cancer cell lines in culture, and delayed tumor growth in cell line xenograft models (PMID: 27196758). 27196758
SRC positive triple-receptor negative breast cancer sensitive KX2-391 + Paclitaxel Preclinical - Cell line xenograft Actionable In a preclinical study, KX2-392 and Taxol (paclitaxel) worked synergistically to inhibit Src signaling and proliferation of triple-receptor negative breast cancer cell lines in culture, and induced tumor regression and suppressed metastasis in xenograft models (PMID: 22784709). 22784709
SRC positive triple-receptor negative breast cancer predicted - sensitive UM-164 Preclinical - Cell line xenograft Actionable In a preclinical study, UM-164 inhibited proliferation and induced apoptosis in human triple-receptor negative breast cancer cell lines with elevated Src activity in culture, and inhibited tumor growth in cell line xenograft models (PMID: 27154914). 27154914
SRC positive non-small cell lung carcinoma predicted - sensitive AC-93253 iodide Preclinical - Cell line xenograft Actionable In a preclinical study, AC-93253 iodide reduced the expression and phosphorylation of Src in non-small cell lung carcinoma cells, which led to antitumor activity, including decreased cell proliferation, cell migration, cell invasion, and colony formation in culture and inhibition of tumor growth in cell line xenograft models (PMID: 29132432). 29132432