Gene Variant Detail

Gene AKT1
Variant E17K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance

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Transcript NM_001014432
gDNA chr14:g.104780214C>T
cDNA c.49G>A
Protein p.E17K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_005267401 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
XM_017021076 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
NM_005163 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
XM_017021078 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
NM_001014432 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
NM_001014431 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
XM_017021077 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38
XM_017021075 chr14:g.104780214C>T c.49G>A p.E17K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 endometrial cancer sensitive ARQ092 Preclinical - Cell line xenograft Actionable In a preclinical study, an endometrial cell line xenograft model harboring AKT E17K was sensitive to ARQ092, demonstrating inhibition of tumor growth (PMID: 26469692). 26469692
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 KRAS wild-type BRAF wild-type colorectal cancer predicted - resistant Cetuximab + Irinotecan Case Reports/Case Series Actionable In a clinical study, 100% (2/2) of colorectal carcinoma patients harboring an AKT1 E17K mutation and wild-type KRAS/BRAF demonstrated resistance to Erbitux (cetuximab) in combination with Camptosar (irinotecan) (PMID: 25714871). 25714871