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Gene Symbol | AKT1 | ||||||||||
Synonyms | AKT | 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). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|---|---|---|---|
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. | |
amp | none | no effect | AKT1 amplification indicates an increased number of copies of the AKT1 gene. However, the mechanism causing the increase is unspecified. | |
D221N | missense | no effect - predicted | AKT1 D221N lies within the protein kinase domain of the Akt1 protein (UniProt.org). D221N is not transforming in cell culture (PMID: 26701849), and therefore, is predicted to have no effect on Akt1 protein function. | |
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, Oct 2020). | |
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). | |
D323N | missense | unknown | AKT1 D323N lies within the protein kinase domain of the Akt1 protein (UniProt.org). D323N has been identified in sequencing studies (PMID: 28634282, PMID: 29335443), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
D323Y | missense | unknown | AKT1 D323Y lies within the protein kinase domain of the Akt1 protein (UniProt.org). D323Y has been identified in the scientific literature (PMID: 26544944), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
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). | |
D44N | missense | no effect - predicted | AKT1 D44N lies within the PH domain of the Akt1 protein (UniProt.org). D44N does not induce tumor formation in xenograft models (PMID: 27147599), and therefore, is predicted to have no effect on the Akt1 protein function. | |
D46H | missense | no effect - predicted | AKT1 D46H lies within the PH domain of the Akt1 protein (UniProt.org). D46H is not transforming in cell culture (PMID: 26701849), and therefore, is predicted to have no effect on Akt1 protein function. | |
D46N | missense | no effect - predicted | AKT1 D46N lies within the PH domain of the Akt1 protein (UniProt.org). D46N is not transforming in cell culture (PMID: 26701849), and therefore, is predicted to have no effect on Akt1 protein function. | |
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). | |
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). | |
E267G | missense | gain of function - predicted | AKT1 E267G lies within the protein kinase domain of the Akt1 protein (UniProt.org). E267G is predicted to confer a gain of function to the Akt1 protein as indicated by promotion of tumor formation in xenograft models (PMID: 27147599). | |
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). | |
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. | |
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. | |
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). | |
E418K | missense | unknown | AKT1 E418K lies within the AGC-kinase C-terminal domain of the Akt1 protein (UniProt.org). E418K has not been characterized in the scientific literature and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
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). | |
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). | |
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). | |
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, Oct 2020). | |
G294R | missense | unknown | AKT1 G294R lies within the protein kinase domain of the Akt1 protein (UniProt.org). G294R has been identified in sequencing studies (PMID: 27369867), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Oct 2020). | |
G311D | missense | unknown | AKT1 G311D lies within the protein kinase domain of the Akt1 protein (UniProt.org). The functional effect of G311D is conflicting as it results in decreased kinase activity, demonstrated by impaired phosphorylation of Akt substrates in cell culture in one study (PMID: 25551293), but results in reduced Akt hydroxylation, increased Akt phosphorylation at T308, and increased colony formation in cell culture in another study (PMID: 27563096). | |
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. | |
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, Oct 2020). | |
inact mut | unknown | loss of function | AKT1 inact mut indicates that this variant results in a loss of function of the Akt1 protein. However, the specific amino acid change has not been identified. | |
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). | |
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). | |
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). | |
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). | |
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). | |
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). | |
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. | |
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. | |
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). | |
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). | |
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). | |
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). | |
L52H | missense | unknown | AKT1 L52H lies within the PH domain of the Akt1 protein (UniProt.org). L52H has been identified in the scientific literature (PMID: 32404308), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
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). | |
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). | |
mutant | unknown | unknown | AKT1 mutant indicates an unspecified mutation in the AKT1 gene. | |
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). | |
N53H | missense | loss of function - predicted | AKT1 N53H lies within the PH domain of the Akt1 protein (UniProt.org). N53H results in decreased cell proliferation and viability compared to wild-type Akt1 in culture (PMID: 29533785), and therefore, is predicted to result in a loss of Akt1 protein function. | |
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. | |
P51L | missense | no effect - predicted | AKT1 P51L lies within the PH domain of the Akt1 protein (UniProt.org). P51L is not transforming in cell culture (PMID: 26701849), and therefore, is predicted to have no effect on Akt1 protein function. | |
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 to the Akt1 protein as demonstrated by increased phosphorylation of Akt1 and downstream phosphorylation of S6 and Pras40 in cell culture (PMID: 29247016). | |
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. | |
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). | |
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). | |
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. | |
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 it demonstrates kinase activity comparable to wild-type Akt1 protein and is not transforming in cell culture (PMID: 23134728), but results in decreased phosphorylation of Akt1 in another study (PMID: 26256536), and therefore, its effect on Akt1 protein function is unknown. | |
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). | |
R23L | missense | unknown | AKT1 R23L lies within the PH domain of the Akt1 protein (UniProt.org). R23L has not been characterized in the scientific literature and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
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). | |
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). | |
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 is not transforming in cultured cells (PMID: 26701849). | |
R465C | missense | unknown | AKT1 R465C lies within the AGC-kinase C-terminal domain of the Akt1 protein (UniProt.org). R465C has been identified in sequencing studies (PMID: 32220884, PMID: 26137586), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Aug 2020). | |
R465H | missense | unknown | AKT1 R465H lies within the AGC-kinase C-terminal domain of the Akt1 protein (UniProt.org). R465H has not been characterized in the scientific literature and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
R48C | missense | unknown | AKT1 R48C lies within the PH domain of the Akt1 protein (UniProt.org). R48C has been identified in the scientific literature (PMID: 31837433), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Feb 2021). | |
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, Oct 2020). | |
S266L | missense | no effect - predicted | AKT1 S266L lies within the protein kinase domain of the Akt1 protein (UniProt.org). S266L is associated with drug resistance in cultured cells (PMID: 30140389), but is not transforming in cell culture (PMID: 26701849), and therefore, is predicted to have no effect on Akt1 protein function. | Y |
S431L | missense | unknown | AKT1 S431L lies within the AGC-kinase C-terminal domain of the Akt1 protein (UniProt.org). S431L has been identified in sequencing studies (PMID: 27994516), but has not been biochemically characterized and therefore, its effect on Akt1 protein function is unknown (PubMed, Nov 2020). | |
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). | |
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, is predicted to have no effect on 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). | |
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). | |
W80A | missense | no effect - predicted | AKT1 W80A lies within the PH domain of the Akt1 protein (UniProt.org). W80A 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 |
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. | |
wild-type | none | no effect | Wild-type AKT1 indicates that no mutation has been detected within the AKT1 gene. | |
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. |