Gene Detail

Gene Symbol AKT1
Synonyms AKT | CWS6 | PKB | PKB-ALPHA | PRKBA | RAC | RAC-ALPHA
Gene Description AKT1, RAC-alpha serine/threonine-protein kinase, is a ubquitously expressed serine-threonine protein kinase, which regulates a variety of cell functions including, metabolism, growth, angiogenesis, cell proliferation and survival through PI3K signaling in response to extracellular signals (PMID: 23297823, PMID: 26698230). Akt1 mutations are observed in a variety of tumor types (PMID: 23134728), including breast cancer (PMID: 30212483), gastric cancer (PMID: 29714127), salivary carcinoma (PMID: 29682203), and overexpression has been observed in osteosarcoma (PMID: 29762834) and gastric cancer (PMID: 29278885).
Entrez Id 207
Chromosome 14
Map Location 14q32.33
Canonical Transcript NM_001014432

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
S266L missense no effect - predicted AKT1 S266L lies within the protein kinase domain of the Akt1 protein (UniProt.org). S266L has not been biochemically characterized, but is not transforming in cell culture and therefore, is predicted to have no effect on the Akt1 protein (PMID: 26701849), but has been associated with drug resistance in cultured cells (PMID: 30140389). Y
K276Q missense loss of function - predicted AKT1 K276Q lies within the protein kinase domain of the Akt1 protein (UniProt.org). K276Q results in decreased SUMOylation of Akt1 in culture (PMID: 23884910) and therefore, is predicted to lead to a loss of Akt1 protein function.
T195I missense gain of function AKT1 T195I lies within the protein kinase domain of the Akt1 protein (UniProt.org). T195I confers a gain of function to the Akt1 protein as demonstrated by increased autophosphorylation and promotion of factor-independent cell survival in culture (PMID: 23134728).
K189N missense gain of function AKT1 K189N lies within the protein kinase domain of the Akt1 protein (UniProt.org). K189N confers a gain of function to the Akt1 protein as demonstrated by increased kinase activity, constitutive downstream signaling, and transformation in cell culture (PMID: 23134728).
N53A missense gain of function - predicted AKT1 N53A lies within the PH domain of the Akt1 protein (UniProt.org). N53A is predicted to confer a gain of function to the Akt1 protein as indicated by increased cell proliferation in culture (PMID: 23134728).
D46H missense no effect - predicted AKT1 D46H lies within the PH domain of the Akt1 protein (UniProt.org). D46H has not been biochemically characterized, but is not transforming in cell culture and therefore, is predicted to have no effect on the Akt1 protein (PMID: 26701849).
L321A missense gain of function AKT1 L321A lies within the protein kinase domain of the Akt1 protein (UniProt.org). L321A confers a gain of function to the Akt1 protein as demonstrated by increased kinase activity and promotion of survival in cell culture (PMID: 23134728).
R370C missense unknown AKT1 R370C lies within the protein kinase domain of the Akt1 protein (UniProt.org). R370C has not been biochemically characterized, however, the effect on Akt1 protein function is conflicting, as it induces tumor formation in xenograft models (PMID: 27147599), but in another assay was is not transforming in cultured cells (PMID: 26701849).
V271A missense gain of function - predicted AKT1 V271A lies within the protein kinase domain of the Akt1 protein (UniProt.org). V271A is predicted to confer a gain of function to the Akt1 protein as indicated by increased cell proliferation in culture (PMID: 23134728).
K14R missense loss of function AKT1 K14R lies within the PH domain of the Akt1 protein (UniProt.org). K14R results in decreased Akt1 kinase activity and phosphorylation of Gsk3beta in culture (PMID: 23884910).
Q79E missense gain of function - predicted AKT1 Q79E lies within the PH domain of the Akt1 protein (UniProt.org). Q79E is predicted to confer a gain of function to the Akt1 protein as indicated by increased cell proliferation in culture (PMID: 23134728).
L78T missense gain of function - predicted AKT1 L78T lies within the PH domain of the Akt1 protein (UniProt.org). L78T is predicted to confer a gain of function to the Akt1 protein as indicated by increase cell proliferation in culture (PMID: 23134728).
D44N missense no effect - predicted AKT1 D44N lies within the PH domain of the Akt1 protein (UniProt.org). D44N has not been biochemically characterized, but does not induce tumor formation in xenograft models and therefore, is predicted to have no effect on the Akt1 protein (PMID: 27147599).
R367C missense no effect - predicted AKT1 R367C lies within the protein kinase domain of the Akt1 protein (UniProt.org). R367C has not been biochemically characterized, but is not transforming in cell culture and therefore, is predicted to have no effect on the Akt1 protein (PMID: 26701849).
G173R missense unknown AKT1 G173R lies within the protein kinase domain of the Akt1 protein (UniProt.org). G173R has been identified in the scientific literature (PMID: 22895070), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Feb 2019).
wild-type none no effect Wild-type AKT1 indicates that no mutation has been detected within the AKT1 gene.
E17K missense gain of function AKT1 E17K lies within the PH domain of the Akt1 protein (UniProt.org). E17K leads to constitutive activation of Akt1, activates downstream signaling, and is transforming in culture (PMID: 17611497, PMID: 29533785, PMID: 27147599, PMID: 26701849).
amp none no effect AKT1 amplification indicates an increased number of copies of the AKT1 gene. However, the mechanism causing the increase is unspecified.
W80R missense gain of function - predicted AKT1 W80R lies within the PH domain of the Akt1 protein (UniProt.org). W80R results in increased repression of FOXO3a compared to wild-type Akt1 in an in vitro assay (PMID: 26137586), and therefore is predicted to result in a gain of Akt1 protein function.
V270A missense gain of function - predicted AKT1 V270A lies within the protein kinase domain of the Akt1 protein (UniProt.org). V270A is predicted to confer a gain of function to the Akt1 protein as indicated by increase cell proliferation in culture (PMID: 23134728).
N53H missense loss of function - predicted AKT1 N53H lies within the PH domain of the Akt1 protein (UniProt.org). N53H has not been biochemically characterized, but results in decreased cell proliferation and viability compared to wild-type Akt1 in culture and is predicted to confer a loss of function to Akt1 (PMID: 29533785).
I19E missense no effect - predicted AKT1 I19E lies within the PH domain of the Akt1 protein (UniProt.org). I19E has no effect on kinase activity of the Akt1 protein in cell culture (PMID: 23134728) and therefore, is predicted to have no effect on the Akt1 protein.
act mut unknown gain of function AKT1 act mut indicates that this variant results in a gain of function in the AKT1 protein. However, the specific amino acid change has not been identified.
D323H missense gain of function AKT1 D323H lies within the protein kinase domain of the Akt1 protein (UniProt.org). D323H results in a gain of function of the Akt1 protein as indicated by increased kinase activity, constitutive downstream signaling, transformation of cultured cells, and tumor growth in xenograft models (PMID: 23134728, PMID: 26701849).
I19L missense unknown AKT1 I19L lies within the PH domain of the Akt1 protein (UniProt.org). I19L has been identified in the scientific literature (PMID: 27601661), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Feb 2019).
over exp none no effect AKT1 over exp indicates an over expression of the Akt1 protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
positive unknown unknown AKT1 positive indicates the presence of the AKT1 gene, mRNA, and/or protein.
Q59E missense no effect - predicted AKT1 Q59E lies within the PH domain of the Akt1 protein (UniProt.org). Q59E demonstrates kinase activity comparable to wild-type Akt1 protein in cell culture (PMID: 23134728) and therefore, is predicted to have no effect on the Akt1 protein.
S246F missense unknown AKT1 S246F lies within the protein kinase domain of the Akt1 protein (UniProt.org). S246F has not been characterized in the scientific literature and therefore, its effect on Akt1 protein function is unknown (PubMed, Feb 2019).
D46N missense no effect - predicted AKT1 D46N lies within the PH domain of the Akt1 protein (UniProt.org). D46N has not been biochemically characterized, but is not transforming in cell culture and therefore, is predicted to have no effect on the Akt1 protein (PMID: 26701849).
E49K missense gain of function AKT1 E49K lies within the PH domain of the Akt1 protein (UniProt.org). E49K results in constitutive activation of Akt1, increased phosphorylation of GSK3-beta, and is transforming in cell culture (PMID: 19802009).
Q79K missense gain of function AKT1 Q79K lies within the PH domain of the Akt1 protein (UniProt.org). Q79K results in increased Akt1 kinase activity, downstream signaling (PMID: 27232857), and is transforming in cell culture (PMID: 23134728, PMID: 23237847).
L52R missense gain of function AKT1 L52R lies within the PH domain of the Akt1 protein (UniProt.org). L52R confers a gain of function to the Akt1 protein as demonstrated by increased kinase activity and downstream signaling, and is transforming in cell culture and xenograft models (PMID: 23134728, PMID: 23237847, PMID: 27147599, PMID: 26701849).
R23A missense gain of function - predicted AKT1 R23A lies within the PH domain of the Akt1 protein (UniProt.org). R23A is predicted to confer a gain of function to the Akt1 protein as indicated by increased cell proliferation (PMID: 23134728).
K276R missense loss of function AKT1 K276R lies within the protein kinase domain of the Akt1 protein (UniProt.org). K276R results in decreased Akt1 kinase activity, reduced phosphorylation of Gsk3beta, and inhibition of cell proliferation in culture (PMID: 23884910).
E278Q missense loss of function - predicted AKT1 E278Q lies within the protein kinase domain of the Akt1 protein (UniProt.org). E278Q results in decreased SUMOylation of Akt1 in culture (PMID: 23884910) and therefore, is predicted to lead to a loss of Akt1 protein function.
L362R missense no effect - predicted AKT1 L362R lies within the protein kinase domain of the Akt1 protein (UniProt.org). L362R is predicted to have no effect on the Akt1 protein as demonstrated by kinase activity comparable to wild-type Akt1 in cell culture (PMID: 23134728).
E40K missense gain of function AKT1 E40K lies within the PH domain of the Akt1 protein (UniProt.org). E40K results in increased Akt1 kinase activity and inhibition of apoptosis in cell culture (PMID: 9690513).
R328A missense gain of function - predicted AKT1 R328A lies within the protein kinase domain of the Akt1 protein (UniProt.org). R328A is predicted to confer a gain of function to the Akt1 protein as indicated by increase cell proliferation in culture (PMID: 23134728).
K276A missense loss of function - predicted AKT1 K276A lies within the protein kinase domain of the Akt1 protein (UniProt.org). K276A results in decreased SUMOylation of Akt1 in culture (PMID: 23884910) and therefore, is predicted to lead to a loss of Akt1 protein function.
Y18S missense no effect - predicted AKT1 Y18S lies within the PH domain of the Akt1 protein (UniProt.org). Y18S demonstrated kinase activity comparable to wild-type Akt1 protein in cell culture (PMID: 23134728) and therefore, is predicted to have no effect on Akt1 protein function.
D325A missense gain of function AKT1 D325A lies within the protein kinase domain of the Akt1 protein (UniProt.org). D325A confers a gain of function to the Akt1 protein as demonstrated by increased kinase activity and promotion of survival in cell culture (PMID: 23134728).
E191A missense gain of function AKT1 E191A lies within the protein kinase domain of the Akt1 protein (UniProt.org). E191A confers a gain of function to the Akt1 protein as demonstrated by increased phosphorylation (PMID: 26256536) and cell proliferation (PMID: 23134728).
mutant unknown unknown AKT1 mutant indicates an unspecified mutation in the AKT1 gene.
K179M missense loss of function AKT1 K179M lies within the protein kinase domain of the Akt1 protein (UniProt.org). K179M results in a loss of function in the Akt1 protein as demonstrated by the lack of kinase activity and the inability to suppress TGF-beta mediated responses (PMID: 7774014, PMID: 9005851, PMID: 16362038).
E278A missense loss of function AKT1 E278A lies within the protein kinase domain of the Akt1 protein (UniProt.org). E278A results in decreased Akt1 kinase activity, reduced phosphorylation of Gsk3beta, and inhibition of cell proliferation in culture (PMID: 23884910).
K183R missense loss of function AKT1 K183R lies within the protein kinase domain of the Akt1 protein (UniProt.org). K183R results in decreased SUMOylation and kinase activity of Akt1 in culture (PMID: 23884910).
K179R missense loss of function AKT1 K179R lies within the protein kinase domain of the Akt1 protein (UniProt.org). K179R results in decreased Akt1 kinase activity and phosphorylation of Gsk3beta in culture (PMID: 23884910).
L202F missense no effect - predicted AKT1 L202F lies within the protein kinase domain of the Akt1 protein (UniProt.org). L202F is predicted to have no effect on the Akt1 protein as demonstrated by kinase activity comparable to wild-type Akt1 in cell culture (PMID: 23134728).
E278S missense loss of function - predicted AKT1 E278S lies within the protein kinase domain of the Akt1 protein (UniProt.org). E278S results in decreased SUMOylation of Akt1 in culture (PMID: 23884910) and therefore, is predicted to lead to a loss of Akt1 protein function.
W80A missense no effect - predicted AKT1 W80A lies within the PH domain of the Akt1 protein (UniProt.org). Akt1 demonstrates phosphorylation and downstream signaling similar to wild-type Akt1 in cell culture (PMID: 25856301), however, is associated with Akt inhibitor resistance (PMID: 18669636, PMID: 25856301). Y
D262G missense unknown AKT1 D262G lies within the protein kinase domain of the Akt1 protein (UniProt.org). D262G has not been characterized in the scientific literature and therefore, its effect on Akt1 protein function is unknown (PubMed, Feb 2019).
F55Y missense gain of function AKT1 F55Y lies within the PH domain of the Akt1 protein (UniProt.org). F55Y confers a gain of function to the Akt1 protein as indicated by increased kinase activity and promotion of survival in cell culture (PMID: 23134728).
P51L missense no effect - predicted AKT1 P51L lies within the PH domain of the Akt1 protein (UniProt.org). P51L has been identified in sequencing studies (PMID: 25148578, PMID: 25303977), but is not transforming in cell culture and therefore, is predicted to have no effect on the Akt1 protein (PMID: 26701849).
V201I missense no effect - predicted AKT1 V201I lies within the protein kinase domain of the Akt1 protein (UniProt.org). V201I does not induce tumor formation in xenograft models (PMID: 27147599), and therefore, its effect on Akt1 protein function is unknown.
D221N missense no effect - predicted AKT1 D221N lies within the protein kinase domain of the Akt1 protein (UniProt.org). D221N has been identified in sequencing studies (PMID: 22820256, PMID: 25957691), but is not transforming in cell culture and therefore, is predicted to have no effect on the Akt1 protein (PMID: 26701849).
R121W missense no effect - predicted AKT1 R121W does not lie within any known functional domains of the Akt1 protein (UniProt.org). R121W results in similar cell proliferation and viability levels as wild-type Akt1 (PMID: 29533785, PMID: 26701849) and therefore, is predicted to have no effect on the Akt1 protein.
E267G missense gain of function - predicted AKT1 E267G lies within the protein kinase domain of the Akt1 protein (UniProt.org). E267G has not been biochemically characterized, but induces tumor formation in xenograft models and therefore, is predicted to confer a gain of function to the Akt1 protein (PMID: 27147599).
K168R missense loss of function AKT1 K168R lies within the protein kinase domain of the Akt1 protein (UniProt.org). K168R results in decreased SUMOylation and kinase activity of Akt1 in culture (PMID: 23884910).
F35L missense loss of function AKT1 F35L lies within the PH domain of the Akt1 protein (UniProt.org). F35L confers a loss of function to the Akt1 protein as demonstrated by decreased Akt1 activity and no effect on cell survival and morphogenesis in cell culture (PMID: 23134728).
P68_C77dup duplication gain of function - predicted AKT1 P68_C77dup indicates the insertion of 10 duplicate amino acids, proline (P)-68 through cysteine (C)-77 in the PH domain of the Akt1 protein (UniProt.org). P68_C77dup is predicted to confer a gain of function on the Akt1 protein as demonstrated by increased phosphorylation of Akt1 and downstream phosphorylation of S6 and PRAS40 in cell culture (PMID: 29247016).
R200A missense unknown AKT1 R200A lies within the protein kinase domain of the Akt1 protein (UniProt.org). The functional effect of R200A is conflicting as R200A demonstrated kinase activity comparable to wild-type Akt1 protein in cell culture (PMID: 23134728), but in another study, R200A had decreased phosphorylation of Akt1, in-vitro (PMID: 26256536).
Molecular Profile Protein Effect Treatment Approaches
AKT1 S266L FGFR1 amp
AKT1 S266L no effect - predicted
AKT1 K276Q loss of function - predicted
AKT1 T195I gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 K189N gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 N53A gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 D46H no effect - predicted
AKT1 L321A gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 R370C unknown Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 V271A gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 K14R loss of function
AKT1 Q79E gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 L78T gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 D44N no effect - predicted
AKT1 R367C no effect - predicted
AKT1 G173R unknown
AKT1 wild-type no effect
AKT1 wild-type PIK3CA wild-type PTEN wild-type
AKT1 E17K FGFR3 Y373C
AKT1 E17K gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 E17K NRAS Q61R
AKT1 E17K BRAF V600X PTEN pos
AKT1 E17K NRAS G12D
AKT1 amp no effect Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 W80R gain of function - predicted
AKT1 V270A gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 N53H loss of function - predicted
AKT1 I19E no effect - predicted
AKT1 act mut gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 D323H gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 I19L unknown
AKT1 over exp PIK3CA E545K
AKT1 over exp no effect
AKT1 over exp PIK3CA H1047R
AKT1 pos NRAS mut
AKT1 positive unknown
AKT1 Q59E no effect - predicted
AKT1 S246F unknown
AKT1 D46N no effect - predicted
AKT1 E49K gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 Q79K BRAF V600X PTEN pos
AKT1 Q79K gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 L52R gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 R23A gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 K276R loss of function
AKT1 E278Q loss of function - predicted
AKT1 L362R no effect - predicted
AKT1 E40K gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 R328A gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 K276A loss of function - predicted
AKT1 Y18S no effect - predicted
AKT1 D325A gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 E191A gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 mutant unknown
AKT1 K179M loss of function
AKT1 E278A loss of function
AKT1 K183R loss of function
AKT1 K179R loss of function
AKT1 L202F no effect - predicted
AKT1 E278S loss of function - predicted
AKT1 W80A no effect - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 D262G unknown
AKT1 F55Y gain of function Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 P51L no effect - predicted
AKT1 V201I no effect - predicted
AKT1 D221N no effect - predicted
AKT1 R121W no effect - predicted
AKT1 E267G gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 K168R loss of function
AKT1 F35L loss of function
AKT1 P68_C77dup gain of function - predicted Akt Inhibitor (Pan) Akt1 Inhibitor
AKT1 R200A unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
AKT1 S266L FGFR1 amp lung cancer predicted - sensitive Uprosertib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring FGFR1 amplification and AKT1 S266L demonstrated sensitivity to Uprosertib (GSK2141795) in culture, showing decreased phosphorylation of Akt1 targets and reduced cell growth (PMID: 30140389). 30140389
AKT1 S266L FGFR1 amp lung cancer predicted - resistant PD173074 Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring FGFR1 amplification demonstrated resistance to increasing concentrations of PD173074 in culture and was subsequently, found to have acquired AKT1 S266L (PMID: 30140389). 30140389
AKT1 wild-type clear cell renal cell carcinoma sensitive Everolimus + RX-0201 Phase Ib/II Actionable In a Phase I/II trial, RX-0201 and Afinitor (everolimus) combination therapy resulted in stable disease in 40% (2/5) of patients with metastatic clear cell renal carcinoma (J Clin Oncol 34, 2016 (suppl 2S; abstr 550)). detail...
AKT1 wild-type ovarian cancer predicted - sensitive Uprosertib Phase I Actionable In a Phase I trial, GSK2141795 treatment resulted in Akt inhibition and clinical benefit in 27% (3/11) of ovarian cancer patients (PMID: 26429956). 26429956
AKT1 wild-type cancer sensitive Uprosertib Preclinical Actionable In a preclinical study, GSK2141795 inhibited all isoforms of AKT in human cancer cell lines (PMID: 23795919). 23795919
AKT1 wild-type PIK3CA wild-type PTEN wild-type triple-receptor negative breast cancer no benefit Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial, Capivasertib (AZD5363) in combination with Taxol (paclitaxel) as first-line therapy resulted in improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) compared to placebo in patients with metastatic triple-negative breast cancer harboring PIK3CA, AKT1, and/or PTEN mutations, but not in patients with wile-type PIK3CA, AKT1, and PTEN (5.3 vs 4.4 months, HR=1.13, p=0.61) (PMID: 30715161; NCT02423603). 30715161
AKT1 E17K FGFR3 Y373C urinary bladder cancer sensitive AZD4547 + Capivasertib Preclinical Actionable In a preclinical study, the combined therapy of AZD5363 and AZD4547 resulted in tumor regression in urinary bladder cancer xenograft models simultaneously harboring the mutations, AKT1 E17K and FGFR3 Y373C (PMID: 26351323). 26351323
AKT1 E17K anal canal cancer sensitive BAY1125976 Preclinical - Pdx Actionable In a preclinical study, treatment with BAY1125976 reduced tumor growth and resulted in partial tumor regression or stable disease in anal cancer patient-derived xenograft (PDX) models harboring AKT1 E17K (PMID: 27699769). 27699769 detail...
AKT1 E17K ovarian carcinoma predicted - sensitive Miransertib Case Reports/Case Series Actionable In a clinical case study, Miransertib (ARQ092) treatment resulted in complete tumor remission and improved quality of life in a patient harboring AKT1 E17K who had Proteus syndrome and developed ovarian carcinoma, and treatment was ongoing at 22 months (PMID: 31058421). 31058421
AKT1 E17K endometrial cancer sensitive Miransertib Preclinical - Cell line xenograft Actionable In a preclinical study, an endometrial cell line xenograft model harboring AKT E17K was sensitive to Miransertib (ARQ092), demonstrating inhibition of tumor growth (PMID: 26469692). 26469692
AKT1 E17K cervical cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with cervical cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K uterus leiomyosarcoma predicted - sensitive Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in a patient with uterus leiomyosarcoma harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K parotid gland cancer predicted - sensitive Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in stable disease over 21 months in a patient with an oncocytic carcinoma of the parotid gland harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K endometrial adenocarcinoma predicted - sensitive Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in a patient with endometrioid adenocarcinoma harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K estrogen-receptor positive breast cancer predicted - sensitive Capivasertib Phase I Actionable In a Phase I trial, Capivasertib (AZD5363) treatment resulted in confirmed partial response in 20% (4/20) and unconfirmed partial response in 10% (2/20) of patients with ESR1-positive breast cancer harboring AKT1 E17K (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K Advanced Solid Tumor sensitive Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in 23% (8/35) and stable disease in 46% (16/35) of patients with advanced solid tumors harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K Advanced Solid Tumor sensitive Capivasertib Phase I Actionable In a Phase I trial, Capivasertib (AZD5363) demonstrated safety and preliminary antitumor activity in patients with advanced solid tumors, resulted in stable disease in 27% (10/37) of patients and partial response in two patients, both of whom harbored an AKT1 E17K mutation (PMID: 26931343; NCT01353781). 26931343 detail...
AKT1 E17K cancer sensitive Uprosertib Preclinical Actionable In a preclinical study, the pan AKT inhibitor GSK2141795 displayed similar levels of inhibition against ATK1 E17K (activating mutation) as ATK1 wild-type (PMID: 24978597). 24978597
AKT1 E17K breast cancer sensitive BAY1125976 Preclinical - Pdx Actionable In a preclinical study, BAY1125976 induced complete tumor regression in a patient-derived xenograft (PDX) model of breast cancer harboring AKT E17K (PMID: 27699769). 27699769
AKT1 E17K triple-receptor negative breast cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with triple-receptor negative breast cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K breast cancer sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, four patients with ESR1-positive breast cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K breast cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, Capivasertib (AZD5363) inhibited growth and colony formation of breast cancer cells expressing AKT E17K in cell culture and in xenografts as well as breast cancer explant models harboring AKT E17K (PMID: 26351323). 26351323
AKT1 E17K endometrial cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, two patients with endometrial cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K Her2-receptor negative breast cancer sensitive Ipatasertib Phase I Actionable In a Phase I trial, a patient with ERBB2 (HER2)-receptor negative breast cancer harboring AKT1 E17K demonstrated a complete metabolic response when treated with Ipatasertib (GDC-0068) (PMID: 27872130). 27872130
AKT1 E17K meningothelial meningioma predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a clinical case study, a patient with meningothelial meningioma harboring AKT1 E17K demonstrated stable disease and some tumor regression when treated with Capivasertib (AZD5363) (PMID: 28376212). 28376212
AKT1 E17K endometrial cancer sensitive ARQ 751 Preclinical - Cell line xenograft Actionable In a preclinical study, an endometrial cell line xenograft model harboring AKT E17K was sensitive to ARQ 751, demonstrating inhibition of tumor growth (PMID: 26469692). 26469692
AKT1 E17K melanoma sensitive Uprosertib Preclinical - Cell culture Actionable In a preclinical study, Uprosertib (GSK2141795) inhibited the growth of melanoma cells harboring AKT1 E17K in culture (PMID: 24735930). 24735930
AKT1 E17K Advanced Solid Tumor no benefit BAY1125976 Phase I Actionable In a Phase I trial, BAY 1125976 treatment demonstrated safety and pharmacological inhibition of Akt signaling, but only resulted in partial response in 1% (1/78) and stable disease in 38% (30/78) of patients with advanced solid tumors, clinical benefit rate at recommended Phase II dose was 27.9% (12/43), and AKT1 E17K mutation status was not associated with response (AACR Annual Meeting 2019, Abstract CT015; NCT01915576). detail...
AKT1 E17K granulosa cell tumor sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with ovarian granulosa cell tumor cancer harboring subclonal AKT E17K demonstrated an overall tumor regression of 24% when treated with AZD5363, which lasted 253 days (PMID: 28489509). 28489509
AKT1 E17K Her2-receptor negative breast cancer predicted - sensitive Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in 23% (8/35) of patients with advanced solid tumors harboring AKT1 E17K mutation, 6 of the patients achieved partial response had hormone receptor-positive, Erbb2 (Her2)-negative breast cancer (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K ovarian endometrial cancer sensitive Capivasertib Phase I Actionable In a Phase I clinical study, a patient with endometrioid ovarian carcinoma harboring AKT1 E17K had a sustained partial response to AZD5363 for more than two years (PMID: 26351323). 26351323
AKT1 E17K breast papillary carcinoma sensitive Capivasertib Phase I Actionable In a Phase I clinical trial, a patient with ER-positive, ERBB2 (HER2)-negative papillary breast carcinoma harboring AKT1 E17K had a sustained partial response to AZD5363 (PMID: 26351323). 26351323
AKT1 E17K lung adenocarcinoma predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with lung adenocarcinoma harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K NRAS Q61R bladder carcinoma sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited Akt activation and downstream signaling in bladder cancer cell lines carrying both Akt1 E17K and Nras Q61R mutations (AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3685). detail...
AKT1 E17K BRAF V600X PTEN pos melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of AKT1 E17K in a wild-type PTEN-expressing BRAF V600-mutant melanoma cell line conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 24265152). 24265152
AKT1 E17K NRAS G12D prostate cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of a prostate cancer cell line harboring AKT E17K and NRAS G12D in culture, and demonstrated antitumor activity in xenograft models (PMID: 27699769). 27699769
AKT1 amp Advanced Solid Tumor predicted - sensitive ONC201 Preclinical - Cell line xenograft Actionable In a preclinical study, ONC201 (TIC-10) inhibited Akt activation and induced apoptosis and tumor regression in a variety of cell line xenograft models (PMID: 23390247). 23390247
AKT1 act mut Advanced Solid Tumor no benefit Triciribine Phase I Actionable In a Phase I trial, Triciribine (API-2) demonstrated safety, but lacked efficacy as a monotherapy in advanced solid tumor patients with activated Akt (PMID: 20644979). 20644979
AKT1 act mut lymphoma decreased response Doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, lymphoma cells overexpressing constitutively active Akt demonstrated reduced sensitivity to Adriamycin (doxorubicin) treatment in cell line xenograft models (PMID: 18708578). 18708578
AKT1 act mut lymphoma no benefit Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) treatment did not improve survival in cell line xenograft animal models of lymphoma overexpressing constitutively active Akt (PMID: 18708578). 18708578
AKT1 act mut lymphoma predicted - sensitive Doxorubicin + Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) and Adriamycin (doxorubicin) combination treatment resulted in improved survival and prolonged remission in cell line xenograft animal models of lymphoma overexpressing constitutively active Akt (PMID: 18708578). 18708578
AKT1 over exp PIK3CA E545K breast cancer resistant Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA E545K resulted in resistance to Pictilisib (GDC-0941) in culture (PMID: 27604488). 27604488
AKT1 over exp PIK3CA H1047R breast cancer resistant Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA H1047R resulted in resistance to Alpelisib (BYL719) in culture (PMID: 27604488). 27604488
AKT1 pos NRAS mut melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing AKT1 demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
AKT1 pos NRAS mut melanoma predicted - resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, two of two NRAS-mutant melanoma cell lines with AKT1 expression demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
AKT1 pos NRAS mut melanoma predicted - resistant Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, two of four NRAS-mutant melanoma cell lines expressing AKT1 were resistant to the combination treatment of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 30819666). 30819666
AKT1 positive ovarian clear cell carcinoma predicted - sensitive Perifosine Preclinical - Cell line xenograft Actionable In a preclinical study, Perifosine (KRX-0401) inhibited Akt1 signaling, inhibited proliferation, and induced apoptosis in human ovarian clear cell cancer cells with activated Akt1 in culture and inhibited tumor growth in cell line xenografts (PMID: 25519148). 25519148
AKT1 positive ovarian clear cell carcinoma predicted - sensitive Cisplatin + Perifosine Preclinical - Cell culture Actionable In a preclinical study, Perifosine (KRX-0401) enhanced the sensitivity of human ovarian clear cell cancer cells with activated Akt1 to Platinol (cisplatin) treatment in culture (PMID: 25519148). 25519148
AKT1 Q79K BRAF V600X PTEN pos melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of AKT1 Q79K in a wild-type PTEN-expressing BRAF V600-mutant melanoma cell line conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 24265152). 24265152
AKT1 Q79K BRAF V600X PTEN pos melanoma sensitive MK2206 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited AKT activation and growth of PTEN-expressing BRAF V600-mutant melanoma cells expressing AKT1 Q79K in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
AKT1 Q79K ovarian cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, an ovarian cancer patient harboring AKT1 Q79K demonstrated tumor regression that lasted 14 months when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 mutant triple-receptor negative breast cancer predicted - sensitive Ipatasertib + Paclitaxel Phase II Actionable In a Phase II trial, Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted in improved progression free survival (6.2 vs 4.9 months) compared to placebo in triple-receptor negative breast cancer patients harboring mutations in PIK3CA, AKT1, or PTEN (J Clin Oncol 35, 2017 (suppl; abstr 1009)). detail...
AKT1 mutant endometrial cancer predicted - sensitive Temsirolimus Phase II Actionable In a retrospective study of a Phase II trial, Torisel (temsirolimus) treatment resulted in an increased progression-free survival (HR 0.16) and response rate (response difference 0.83) in advanced endometrial cancer patients harboring AKT1 mutations (PMID: 27016228). 27016228
AKT1 mutant invasive bladder transitional cell carcinoma predicted - resistant Cisplatin + Gemcitabine + Sorafenib Phase II Actionable In a Phase II trial, AKT1 mutations were more frequent in muscle-invasive urothelial bladder cancer patients that did not respond to Nexavar (sorafenib), Platinol (cisplatin) and Gemzar (gemcitabine) combination therapy than those who did respond (J Clin Oncol 35, 2017 (suppl 6S; abstract 345)). detail...
AKT1 mutant triple-receptor negative breast cancer predicted - sensitive Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial, Capivasertib (AZD5363) in combination with Taxol (paclitaxel) as first-line therapy resulted in improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) compared to placebo in patients with metastatic triple-negative breast cancer harboring PIK3CA, AKT1, and/or PTEN mutations, but not in patients with wile-type PIK3CA, AKT1, and PTEN (5.3 vs 4.4 months, HR=1.13, p=0.61) (PMID: 30715161; NCT02423603). 30715161
AKT1 mutant endometrial cancer sensitive GDC-0980 Phase II Actionable In a Phase II trial, Apitolisib (GDC-0980) was poorly tolerated, but demonstrated efficacy in endometrial cancer patients harboring mutations in PIK3CA, PTEN, or AKT1 (J Clin Oncol 32:5s, 2014 (suppl; abstr 5513)). detail...
AKT1 W80A breast cancer resistant MK2206 Preclinical Actionable In a preclinical study, breast cancer cells expressing AKT1 W80A were resistant to MK2206 in culture, resulting in repression of induced cell death when compared to wild-type AKT1 (PMID: 25551293). 25551293
AKT1 W80A Advanced Solid Tumor resistant MK2206 Preclinical - Cell culture Actionable In a preclinical study, transformed mouse adipocytes expressing human Akt1 W80A were resistant to the AKT inhibitor, MK-2206 (PMID: 25856301). 25856301
AKT1 P68_C77dup breast cancer sensitive Capivasertib Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing AKT1 P68_C77dup demonstrated sensitivity by AZD5363 in culture, resulting in decreased cell survival (PMID: 29247016). 29247016