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Gene POLE
Variant R114*
Impact List nonsense
Protein Effect loss of function - predicted
Gene Variant Descriptions POLE R114* results in a premature truncation of the Pole protein at amino acid 114 of 2286 (UniProt.org). R114* has not been biochemically characterized however, due to the effects of other truncation mutations downstream of R114 (PMID: 36402816), is predicted to lead to a loss of Pole protein function.
Associated Drug Resistance
Category Variants Paths

POLE mutant POLE inact mut POLE R114*

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Transcript NM_006231.4
gDNA chr12:g.132680037G>A
cDNA c.340C>T
Protein p.R114*
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_006231 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534799.3 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
NM_006231.4 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534799.2 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534800 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534795 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534795.3 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534799 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_047429018.1 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
NM_006231.3 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38
XM_011534795.4 chr12:g.132680037G>A c.340C>T p.R114* RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
POLE inact mut colorectal cancer not applicable N/A Guideline Prognostic POLE inactivating mutations are associated with a more favorable prognosis in patients with colorectal cancer (NCCN.org). detail...
POLE inact mut rectum cancer sensitive Pembrolizumab Guideline Actionable Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with advanced or metastatic rectal cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut small intestine adenocarcinoma sensitive Pembrolizumab Guideline Actionable Keytruda (pembrolizumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut small intestine adenocarcinoma sensitive Ipilimumab + Nivolumab Guideline Actionable Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut rectum cancer sensitive Dostarlimab-gxly Guideline Actionable Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic rectal cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut small intestine adenocarcinoma sensitive Dostarlimab-gxly Guideline Actionable Jemperli (dostarlimab-gxly) is included in guidelines as a subsequent therapy for patients with advanced or metastatic small bowel adenocarcinoma harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut rectum cancer sensitive Ipilimumab + Nivolumab Guideline Actionable Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as systemic therapy for patients with advanced or metastatic rectal cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut small intestine adenocarcinoma sensitive Nivolumab Guideline Actionable Opdivo (nivolumab) is included in guidelines as an initial therapy for patients with advanced or metastatic small bowel adenocarcinoma harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut rectum cancer sensitive Nivolumab Guideline Actionable Opdivo (nivolumab) is included in guidelines as systemic therapy for patients with advanced or metastatic rectal cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut colon cancer sensitive Ipilimumab + Nivolumab Guideline Actionable Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as systemic therapy for patients with advanced or metastatic colon cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut colon cancer sensitive Dostarlimab-gxly Guideline Actionable Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic colon cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut colorectal carcinoma not applicable N/A Guideline Risk Factor Germline POLE inactivating mutations result in polymerase proofreading-associated polyposis and are associated with increased risk of developing colorectal carcinoma (NCCN.org). detail...
POLE inact mut colorectal cancer predicted - sensitive unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a clinical study, immunotherapy resulted in improved clinical benefit in patients with metastatic colorectal cancer harboring POLE inactivating mutations (n=7, 3 complete responses, 3 partial responses, 1 stable disease (SD)) and durable response (remained on therapy with median follow up of 36 months) compared to microsatellite stable (MSS) patients harboring non-loss-of-function POLE mutations (n=7, 2 SD; median progression-free survival 3.6 months, p<0.0003) (Ann Oncol (2023) 34 (suppl_2): S448-S449). detail...
POLE inact mut colon cancer sensitive Nivolumab Guideline Actionable Opdivo (nivolumab) is included in guidelines as systemic therapy for patients with advanced or metastatic colon cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE inact mut Advanced Solid Tumor predicted - sensitive Nivolumab Case Reports/Case Series Actionable In a Phase II trial, Opdivo (nivolumab) resulted in an objective response rate (ORR) of 38% (7/19; all partial responses) and a disease control rate (DCR) of 58% (11/19) at 12 weeks in patients with advanced solid tumors harboring a POLE mutation, and among assessable patients with an inactivating POLE mutation, along with high tumor mutational burden, treatment resulted in an ORR of 46% (5/11) and a DCR of 73% (8/11) (PMID: 35398880; NCT03012581). 35398880
POLE inact mut colon cancer sensitive Pembrolizumab Guideline Actionable Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with advanced or metastatic colon cancer harboring POLE inactivating mutations (NCCN.org). detail...
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified CTLA4 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061
POLE mutant Advanced Solid Tumor predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, immune checkpoint inhibitor (ICI) treatment, including CTLA4, PD-1, and PD-L1-targeting antibodies, resulted in prolonged overall survival (34 vs 18 months, p=0.004) in patients with advanced solid tumors harboring POLE or POLD1 mutations compared to wild-type patients, and POLE/POLD1 mutation served as a predictor of response to ICI (p=0.047, HR=1.41) independent of MSI-H status (PMID: 31415061). 31415061