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Gene KEAP1
Variant G332C
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions KEAP1 G332C lies within Kelch repeat 1 of the Keap1 protein (UniProt.org). G332C results in loss of Nfe2l2 inhibition leading to increased Nfe2l2 target gene and protein expression and increased cell survival following irradiation and hydrogen peroxide treatment in culture (PMID: 33071215).
Associated Drug Resistance
Category Variants Paths

KEAP1 mutant KEAP1 inact mut KEAP1 G332C

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Transcript NM_203500.2
gDNA chr19:g.10491908C>A
cDNA c.994G>T
Protein p.G332C
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_011528452.1 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38
NM_203500.1 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38
NM_012289.4 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38
NM_203500.2 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38
XM_005260173.1 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38
XM_005260174.1 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38
NM_012289.3 chr19:g.10491908C>A c.994G>T p.G332C RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KEAP1 inact mut lung adenocarcinoma sensitive MSU38225 Preclinical - Cell culture Actionable In a preclinical study, MSU38225 inhibited Nrf2 transcriptional activity and downstream pathway activation, increased Nrf2 degradation, and inhibited growth of lung cancer cells harboring a KEAP1 inactivating mutation in 2D and 3D culture (PMID: 34158350). 34158350
KEAP1 inact mut gallbladder cancer resistant Fluorouracil Preclinical Actionable In a preclinical study, gallbladder cancer cells harboring KEAP inactivating mutations had increased NRF2 activation and demonstrated resistance to Adrucil (fluorouracil) in culture (PMID: 18692501). 18692501
KEAP1 inact mut lung adenocarcinoma sensitive Carboplatin + MSU38225 Preclinical - Cell line xenograft Actionable In a preclinical study, MSU38225 and Paraplatin (carboplatin) combination treatment synergistically inhibited growth of a lung cancer cell line harboring a KEAP1 inactivating mutation in culture and slowed tumor growth in a cell line xenograft model compared to vehicle or Paraplatin (carboplatin) alone (PMID: 34158350). 34158350
KEAP1 inact mut lung adenocarcinoma sensitive Fluorouracil + MSU38225 Preclinical - Cell culture Actionable In a preclinical study, MSU38225 and Adrucil (fluorouracil) combination treatment inhibited growth of a lung cancer cell line harboring a KEAP1 inactivating mutation in culture (PMID: 34158350). 34158350
KEAP1 mutant lung adenocarcinoma not predictive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring a KEAP1 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 when treated with an unspecified PD-L1 antibody, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
KEAP1 mutant lung non-squamous non-small cell carcinoma predicted - sensitive Camrelizumab + Rivoceranib Phase Ib/II Emerging In a Phase Ib/II trial, non-squamous NSCLC patients harboring KEAP1 and/or STK11 mutations (n=14) demonstrated an improved 12-month survival rate (85.1% vs 53.1%; p=0.01), and a trend towards improved objective response rate (42.9% vs 28.1%; p=0.33), disease control rate (92.9% vs 65.6%, p=0.053), and median progression-free survival (9.4 vs 5.3 months; p=0.64) compared to wild-type KEAP1/STK11 patients (n=32) treated with Camrelizumab (SHR-1210) plus Rivoceranib (apatinib) (PMID: 33323401; NCT03083041). 33323401
KEAP1 mutant lung adenocarcinoma sensitive Radiotherapy + Telaglenastat Preclinical - Cell culture Actionable In a preclinical study, Telaglenstat (CB-839) increased sensitivity of a non-small cell lung cancer cell line harboring a KEAP1 mutation to radiotherapy in culture (PMID: 33071215). 33071215
KEAP1 mutant lung adenocarcinoma not predictive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, lung adenocarcinoma patients harboring a KEAP1 mutation demonstrated a shorter progression free survival compared to patients with wild-type KEAP1 when treated with an unspecified PD-1 antibody, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). 32312757
KEAP1 mutant lung non-small cell carcinoma predicted - resistant Radiotherapy Clinical Study - Cohort Actionable In a clinical study, non-small cell lung cancer patients harboring KEAP1 or NFE2L2 mutations (n=9) demonstrated higher incidence of local recurrence at 30-months after radiotherapy (70% vs 18%, p<0.003) compared to KEAP1/NFE2L2 wild-type patients (n=33) (PMID: 27663899). 27663899
KEAP1 mutant lung squamous cell carcinoma predicted - sensitive Sapanisertib Case Reports/Case Series Actionable In a Phase II trial, Sapanisertib (MLN0128) treatment resulted in a disease control rate of 66% (2/3, 2 stable disease) in lung squamous cell carcinoma patients harboring KEAP1 mutations (J Clin Oncol 37, 2019 (suppl; abstr 9085)). detail...