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Gene Symbol | POLE | ||||||||||
Synonyms | CRCS12 | FILS | IMAGEI | POLE1 | ||||||||||
Gene Description | POLE, DNA polymerase epsilon catalytic subunit, mediates proofreading activity during DNA repair and replication (PMID: 26822575, PMID: 29604063) and plays a role in genomic stability (PMID: 31747945). Somatic mutations in POLE have been identified in colorectal cancer (PMID: 29998005, PMID: 29072370), frequently in endometrial cancer (PMID: 26822575, PMID: 28795426, PMID: 30733993), and are often associated with high tumor mutational burden (PMID: 30733993, PMID: 29880869), but are less likely to be associated with DNA mismatch repair (MMR) deficiency (PMID: 30585826). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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A426V | missense | unknown | POLE A426V lies within the exonuclease domain of the Pole protein (PMID: 29352080). A426V has been identified in the scientific literature (PMID: 25224212), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
A456P | missense | unknown | POLE A456P lies within the exonuclease domain of the Pole protein (PMID: 29352080). A456P has been identified in the scientific literature (PMID: 31829442), but has not been biochemically characterized, and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
A456T | missense | unknown | POLE A456T lies within the exonuclease domain of the Pole protein (PMID: 29352080). A456T has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
D275A | missense | unknown | POLE D275A lies within the exonuclease domain of the Pole protein (PMID: 29352080). D275A results in increased nucleotide error rates in combination with E277A compared to wild-type Pole (PMID: 29488881, PMID: 29559562), but has not been individually characterized and therefore, its effect on Pole protein function is unknown. | |
D301N | missense | unknown | POLE D301N lies within the exonuclease domain of the Pole protein (PMID: 29352080). D301N has been identified in the scientific literature (PMID: 30917185), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
D368N | missense | loss of function - predicted | POLE D368N lies within the exonuclease domain of the Pole protein (PMID: 29352080). D368N (corresponds to D383N in yeast) results in increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
E277A | missense | unknown | POLE E277A lies within the exonuclease domain of the Pole protein (PMID: 29352080). E277A results in increased nucleotide error rates in combination with D275A compared to wild-type Pole (PMID: 29488881, PMID: 29559562), but has not been individually characterized and therefore, its effect on Pole protein function is unknown. | |
E277V | missense | unknown | POLE E277V lies within the exonuclease domain of the Pole protein (PMID: 29352080). E277V has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 20211). | |
E396G | missense | unknown | POLE E396G lies within the exonuclease domain of the Pole protein (PMID: 29352080). E396G has been identified in the scientific literature (PMID: 26763250, PMID: 31829442), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
F2251L | missense | unknown | POLE F2251L does not lie within any known functional domains of the Pole protein (UniProt.org). F2251L has been identified in the scientific literature (PMID: 32098697), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
F285L | missense | unknown | POLE F285L lies within the exonuclease domain of the Pole protein (PMID: 29352080). F285L has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
F285S | missense | unknown | POLE F285S lies within the exonuclease domain of the Pole protein (PMID: 29352080). F285S has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
F367C | missense | unknown | POLE F367C lies within the exonuclease domain of the Pole protein (PMID: 29352080). F367C has been identified in the scientific literature (PMID: 26763250, PMID: 31240875), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
F367L | missense | unknown | POLE F367L lies within the exonuclease domain of the Pole protein (PMID: 29352080). F367L has been identified in the scientific literature (PMID: 26763250, PMID: 28061006, PMID: 31829442), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
F367S | missense | loss of function | POLE F367S lies within the exonuclease domain of the Pole protein (PMID: 29352080). F367S results in reduced exonuclease activity and increased replication error rates compared to wild-type Pole in in vitro assays (PMID: 29352080, PMID: 25228659). | |
G433D | missense | unknown | POLE G433D lies within the exonuclease domain of the Pole protein (PMID: 29352080). G433D has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
H475R | missense | unknown | POLE H475R does not lie within any known functional domains of the Pole protein (PMID: 29352080). H475R has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
inact mut | unknown | loss of function | POLE inact mut indicates that this variant results in a loss of function of the Pole protein. However, the specific amino acid change has not been identified. | |
K425R | missense | loss of function - predicted | POLE K425R lies within the exonuclease domain of the Pole protein (PMID: 29352080). K425R (corresponds to K440R in yeast) results in significantly increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
K429R | missense | unknown | POLE K429R lies within the exonuclease domain of the Pole protein (PMID: 29352080). K429R has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
L424I | missense | loss of function - predicted | POLE L424I lies within the exonuclease domain of the Pole protein (PMID: 29352080). L424I results in reduced exonuclease activity in an in vitro assay (PMID: 29056344), and therefore, is predicted to lead to a loss of Pole protein function. | |
L424P | missense | unknown | POLE L424P lies within the exonuclease domain of the Pole protein (PMID: 29352080). L424P has been identified in the scientific literature (PMID: 26763250, PMID: 31829442), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
L424V | missense | loss of function | POLE L424V lies within the exonuclease domain of the Pole protein (PMID: 29352080). L424V (corresponds to L439V in yeast) results in increased mutagenesis in yeast assays (PMID: 32424176), and results in reduced exonuclease activity in an in vitro assay (PMID: 29056344). | |
L455Q | missense | unknown | POLE L455Q lies within the exonuclease domain of the Pole protein (PMID: 29352080). A456T has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
M294R | missense | loss of function - predicted | POLE M294R lies within the exonuclease domain of the Pole protein (PMID: 29352080). M294R (corresponds to M309R in yeast) results in increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
M487V | missense | unknown | POLE M487V does not lie within any known functional domains of the Pole protein (PMID: 29352080). M487V has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
mutant | unknown | unknown | POLE mutant indicates an unspecified mutation in the POLE gene. | |
N363K | missense | loss of function - predicted | POLE N363K lies within the exonuclease domain of the Pole protein (PMID: 29352080). N363K (corresponds to N378K in yeast) results in significantly increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
P269fs | frameshift | loss of function - predicted | POLE P269fs results in a change in the amino acid sequence of the Pole protein beginning at 269 of 2286, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the polymerase domain (PMID: 29352080), P269fs is predicted to lead to a loss of Pole protein function. | |
P286H | missense | loss of function | POLE P286H lies within the exonuclease domain of the Pole protein (PMID: 29352080). P286H results in reduced exonuclease activity and increased replication error rates compared to wild-type Pole in in vitro assays (PMID: 29352080, PMID: 25228659). | |
P286L | missense | loss of function - predicted | POLE P286L lies within the exonuclease domain of the Pole protein (PMID: 29352080). P286L (corresponds to P301L in yeast) results in significantly increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
P286R | missense | loss of function | POLE P286R lies within the exonuclease domain of the Pole protein (PMID: 29352080). P286R is associated with hypermutation in patient samples (PMID: 27612425, PMID: 23528559), results in a perturbation of the DNA-binding pocket by structural modeling (PMID: 23528559), and confers impaired exonuclease activity and increased mutation rate compared to wild-type Pole in vitro (PMID: 25228659, PMID: 29352080). | |
P286S | missense | unknown | POLE P286S lies within the exonuclease domain of the Pole protein (PMID: 29352080). P286S has been identified in the scientific literature (PMID: 26648449, PMID: 28061006, PMID: 31829442), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Mar 2020). | |
P286T | missense | unknown | POLE P286T lies within the exonuclease domain of the Pole protein (PMID: 29352080). P286T has been identified in the scientific literature (PMID: 29320758, PMID: 29316426), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
P324L | missense | loss of function - predicted | POLE P324L lies within the exonuclease domain of the Pole protein (PMID: 29352080). P324L (corresponds to P339L in yeast) results in increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
P436R | missense | loss of function - predicted | POLE P436R lies within the exonuclease domain of the Pole protein (PMID: 29352080). P436R results in increased mutation rates compared to wild-type Pole protein in a yeast assay (PMID: 29352080), and therefore, is predicted to result in a loss of Pole protein function. | |
P436S | missense | loss of function - predicted | POLE P436S lies within the exonuclease domain of the Pole protein (PMID: 29352080). P436S (corresponds to P451S in yeast) results in increased mutagenesis in yeast assays (PMID: 32424176), and therefore, is predicted to result in a loss of Pole protein function. | |
P441L | missense | unknown | POLE P441L lies within the exonuclease domain of the Pole protein (PMID: 29352080). P441L has been identified in the scientific literature (PMID: 26763250, PMID: 29572003, PMID: 31829442), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
P476L | missense | unknown | POLE P476L does not lie within any known functional domains of the Pole protein (PMID: 29352080). H475R has been identified in the scientific literature (PMID: 25124163), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
Q2217* | nonsense | unknown | POLE Q2217* results in a premature truncation of the Pole protein at amino acid 2217 of 2286 (UniProt.org). Q2217* has not been characterized in the scientific literature and therefore, its effect on Pole protein function is unknown (PubMed, Nov 2020). | |
Q303R | missense | unknown | POLE Q303R lies within the exonuclease domain of the Pole protein (PMID: 29352080). Q303R has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
R114* | nonsense | loss of function - predicted | POLE R114* results in a premature truncation of the Pole protein at amino acid 114 of 2286 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), R114* is predicted to lead to a loss of Pole protein function. | |
R1508H | missense | unknown | POLE R1508H does not lie within any known functional domains of the Pole protein (UniProt.org). R1508H has been identified in sequencing studies (PMID: 29458332), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
R1519C | missense | unknown | POLE R1519C does not lie within any known functional domains of the Pole protein (UniProt.org). R1519C has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
R1519H | missense | unknown | POLE R1519H does not lie within any known functional domains of the Pole protein (UniProt.org). R1519H has not been characterized in the scientific literature and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
R1519L | missense | unknown | POLE R1519L does not lie within any known functional domains of the Pole protein (UniProt.org). R1519L has not been characterized in the scientific literature and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
R446W | missense | unknown | POLE R446W lies within the exonuclease domain of the Pole protein (PMID: 29352080). R446W has been identified in the scientific literature (PMID: 25224212), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
S297A | missense | unknown | POLE S297A lies within the exonuclease domain of the Pole protein (PMID: 29352080). S297A has been identified in sequencing studies (PMID: 26763250), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
S297F | missense | unknown | POLE S297F lies within the exonuclease domain of the Pole protein (PMID: 29352080). S297F has been identified in the scientific literature (PMID: 29559562, PMID: 27491810, PMID: 24844595), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Jan 2021). | |
S297Y | missense | unknown | POLE S297Y lies within the exonuclease domain of the Pole protein (PMID: 29352080). S297Y has been identified in sequencing studies (PMID: 31240875), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Jan 2021). | |
S459F | missense | loss of function | POLE S459F lies within the exonuclease domain of the Pole protein (PMID: 29352080). S459F results in loss of exonuclease activity in human cells (PMID: 25228659) and increased mutation rates in yeast assays compared to wild-type Pole (PMID: 29352080). | |
S459Y | missense | unknown | POLE S459Y lies within the exonuclease domain of the Pole protein (PMID: 29352080). S459Y has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
T278K | missense | unknown | POLE T278K lies within the exonuclease domain of the Pole protein (PMID: 29352080). T278K has not been characterized in the scientific literature and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
T278P | missense | unknown | POLE T278P lies within the exonuclease domain of the Pole protein (PMID: 29352080). T278P has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
T278S | missense | unknown | POLE T278S lies within the exonuclease domain of the Pole protein (PMID: 29352080). T278S has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
T279A | missense | unknown | POLE T279A lies within the exonuclease domain of the Pole protein (PMID: 29352080). T279A has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
T323A | missense | unknown | POLE T323A lies within the exonuclease domain of the Pole protein (PMID: 29352080). T323A has been identified in the scientific literature (PMID: 29386312), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Jan 2021). | |
T457L | missense | unknown | POLE T457L lies within the exonuclease domain of the Pole protein (PMID: 29352080). T457L has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
T457M | missense | unknown | POLE T457M lies within the exonuclease domain of the Pole protein (PMID: 29352080). T457M has been identified in the scientific literature (PMID: 30917185), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). | |
V1426I | missense | unknown | POLE V1426I does not lie within any known functional domains of the Pole protein (UniProt.org). V1426I has been identified in sequencing studies (PMID: 30171174), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
V411L | missense | loss of function - predicted | POLE V411L lies within the exonuclease domain of the Pole protein (PMID: 29352080). V411L results in reduced Pole exonuclease activity in an in vitro assay (PMID: 25228659), and therefore, is predicted to lead to a loss of Pole protein function. | |
V411M | missense | unknown | POLE V411M lies within the exonuclease domain of the Pole protein (PMID: 29352080). V411M has been identified in in the scientific literature (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
V411R | missense | unknown | POLE V411R lies within the exonuclease domain of the Pole protein (PMID: 29352080). V411R has been identified in the scientific literature (PMID: 30194485), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
V533M | missense | unknown | POLE V533M lies within the polymerase domain of the Pole protein (PMID: 29352080). V533M has been identified in the scientific literature (PMID: 32098697), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Sep 2020). | |
W410* | nonsense | loss of function - predicted | POLE W410* results in a premature truncation of the Pole protein at amino acid 410 of 2286 (UniProt.org). Due to the loss of the polymerase domain (PMID: 29352080), W410* is predicted to lead to a loss of Pole protein function. | |
wild-type | none | no effect | Wild-type POLE indicates that no mutation has been detected within the POLE gene. | |
Y434N | missense | unknown | POLE Y434N lies within the exonuclease domain of the Pole protein (PMID: 29352080). Y434N has been identified in sequencing studies (PMID: 32801757), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2021). |