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Gene Symbol POLD1
Synonyms CDC2 | CRCS10 | MDPL | POLD
Gene Description POLD1, DNA polymerase delta 1, catalytic subunit, is the catalytic subunit and the largest of four subunits that form the DNA polymerase delta holoenzyme, which mediates DNA replication (PMID: 27320729) and repair (PMID: 30625304). Germline and somatic mutations in POLD1 have been identified in a variety of human cancers (PMID: 27320729), including colorectal cancer (PMID: 31769227) and lung cancer (PMID: 31673068), and may be associated with high tumor mutational burden and response to immunotherapy (PMID: 31741177, PMID: 31673068, PMID: 31415061, PMID: 30524909).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
5424 19 19q13.33 NM_002691 Tumor suppressor (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A935T missense unknown POLD1 A935T does not lie within any known functional domains of the Pold1 protein (UniProt.org). A935T has been identified in sequencing studies (PMID: 29056344), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Oct 2022).
C319G missense unknown POLD1 C319G lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). C319G has been identified in the scientific literature (PMID: 30827058), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Feb 2023).
E374K missense unknown POLD1 E374K lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). E374K has been identified in the scientific literature (PMID: 31866764), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Feb 2023).
G1100R missense loss of function - predicted POLD1 G1100R does not lie within any known functional domains of the Pold1 protein (UniProt.org). G1100R demonstrates exonuclease activity similar to wild-type Pold1, but results in decreased polymerase activity in in vitro assays (PMID: 31944473), and therefore, is predicted to lead to a loss of Pold1 protein function.
G321S missense unknown POLD1 G321S lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). G321S has been identified in the scientific literature (PMID: 30827058, PMID: 26648449), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Feb 2023).
I1070N missense loss of function - predicted POLD1 I1070N lies within the CysB motif of the Pold1 protein (UniProt.org). I1070N results in decreased interaction with DNA polymerase complex subunits in in vitro assays (PMID: 31944473), and therefore, is predicted to lead to a loss of Pold1 protein function.
inact mut unknown loss of function POLD1 inact mut indicates that this variant results in a loss of function of the Pold1 protein. However, the specific amino acid change has not been identified.
K486N missense unknown POLD1 K486N does not lie within any known functional domains of the Pold1 protein (UniProt.org). K486N has been identified in the scientific literature (PMID: 34954152), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Sep 2022).
L210P missense unknown POLD1 L210P does not lie within any known functional domains of the Pold1 protein (UniProt.org). L210P has been identified in the scientific literature (PMID: 34954152), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Sep 2022).
L474P missense unknown POLD1 L474P lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). L474P has been associated with increased single-base substitution in patient cells (PMID: 34594041), but has not been biochemically characterized and therefore, its effect on Pole protein function is unknown (PubMed, Feb 2023).
mutant unknown unknown POLD1 mutant indicates an unspecified mutation in the POLD1 gene.
P327L missense loss of function - predicted POLD1 P327L lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). P327L demonstrates polymerase activity similar to wild-type Pold1 protein, but results in decreased exonuclease activity in in vitro assays (PMID: 31944473), and therefore, is predicted to lead to a loss of Pold1 protein function.
Q411* nonsense loss of function - predicted POLD1 Q411* results in a premature truncation of the Pold1 protein at amino acid 411 of 1107 (UniProt.org). Due to loss of the CysA-type zinc finger domain (UniProt.org), Q411* is predicted to lead to a loss of Pold1 protein function.
R1060C missense loss of function POLD1 R1060C lies within the CysB motif of the Pold1 protein (UniProt.org). R1060C confers a loss of function to the Pold1 protein as indicated by decreased Pold1 protein expression, impaired formation of the protein-protein interactions with the DNA replication complex, and reduced cell proliferation and DNA replication in culture (PMID: 31629014).
R689W missense loss of function POLD1 R689W does not lie within any known functional domains of the Pold1 protein (UniProt.org). R689W confers a loss of function to Pold1 protein as indicated by reduced selectivity of nucleotides in an in vitro assay and increased mutation frequency compared to wild-type Pold1 in cell culture (PMID: 28368425), and the corresponding yeast variant (R696W) results in an increase in spontaneous mutations and is lethal in yeast assays (PMID: 19966286).
S197Hfs*54 frameshift loss of function - predicted POLD1 S197Hfs*54 indicates a shift in the reading frame starting at amino acid 197 and terminating 54 residues downstream causing a premature truncation of the 1107 amino acid Pold1 protein (UniProt.org). S197Hfs*54 results in decreased Pold1 protein expression and polymerase activity in a patient derived cell line harboring a co-occurring POLD1 G1100R (PMID: 31944473), and is predicted to lead to a loss of Pold1 protein function due to the loss of all known functional domains (PMID: 27093186).
S478N missense loss of function POLD1 S478N lies within the exonuclease domain of the Pold1 protein (PMID: 27093186). S478N demonstrates polymerase activity similar to wild-type Pold1 protein, but results in decreased exonuclease activity in in vitro assays (PMID: 31944473) and in yeast (PMID: 23263490).
S605del deletion loss of function POLD1 S605del results in the deletion of an amino acid within the polymerase active site of the Pold1 protein at amino acid 605 (PMID: 23770608). S605del results in a loss of Pold1 DNA polymerase activity and decreased exonuclease activity in in vitro assays (PMID: 23770608), and is associated with altered nuclear morphology, increased senescence, and impaired DNA damage repair in patient-derived cells (PMID: 30388038).
V1025L missense unknown POLD1 V1025L lies within the CysA-type zinc finger domain of the Pold1 protein (UniProt.org). V1025L has been identified in sequencing studies (PMID: 29056344, PMID: 28363643), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Feb 2023).
V295M missense unknown POLD1 V295M does not lie within any known functional domains of the Pold1 protein (UniProt.org). V295M has been identified in the scientific literature (PMID: 34285382), but has not been biochemically characterized and therefore, its effect on Pold1 protein function is unknown (PubMed, Oct 2022).