POLD1

Summary

POLD1 (DNA polymerase delta 1, catalytic subunit, HGNC:9175) is a protein-coding gene on chromosome 19q13.33, encoding DNA polymerase delta catalytic subunit (P28340). As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. In precision oncology, POLD1 C284Y confers sensitivity to Pembrolizumab in Lung Adenocarcinoma (CIViC Level C); 1 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3’ to 5’ exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6.

Source: NCBI Gene 5424 — RefSeq curated summary.

At a glance

• Gene–disease (curated): POLD1-related polyposis and colorectal cancer syndrome (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 5,828 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 110
• Druggable target: yes
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002691

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9175
Approved symbol	POLD1
Name	DNA polymerase delta 1, catalytic subunit
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	CDC2
Ensembl gene	ENSG00000062822
Ensembl biotype	protein_coding
OMIM	174761
Entrez	5424

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 38 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000440232, ENST00000593407, ENST00000593887, ENST00000593981, ENST00000595904, ENST00000596221, ENST00000596648, ENST00000597963, ENST00000599857, ENST00000600746, ENST00000600859, ENST00000601098, ENST00000613923, ENST00000643407, ENST00000644560, ENST00000687454, ENST00000869776, ENST00000869777, ENST00000869778, ENST00000869779, ENST00000869780, ENST00000869781, ENST00000869782, ENST00000869783, ENST00000935843, ENST00000935844, ENST00000935845, ENST00000935846, ENST00000935847, ENST00000935848, ENST00000935849, ENST00000935850, ENST00000935851, ENST00000935852, ENST00000935853, ENST00000935854, ENST00000935855, ENST00000935856, ENST00000935857, ENST00000935858, ENST00000935859, ENST00000969648, ENST00000969649, ENST00000969650

RefSeq mRNA: 3 — MANE Select: NM_002691 NM_001256849, NM_001308632, NM_002691

CCDS: CCDS12795, CCDS82381

Canonical transcript exons

ENST00000440232 — 27 exons

Exon	Start	End
ENSE00000395666	50406983	50407174
ENSE00000721930	50409519	50409666
ENSE00000721946	50409122	50409235
ENSE00000721974	50407327	50407415
ENSE00000721979	50406407	50406517
ENSE00000721982	50406182	50406322
ENSE00000869281	50403493	50403597
ENSE00000869282	50403053	50403219
ENSE00000869283	50402612	50402741
ENSE00000869285	50402205	50402373
ENSE00000869286	50401999	50402124
ENSE00000954761	50413426	50413521
ENSE00000954762	50413742	50413879
ENSE00000954763	50414815	50414990
ENSE00000954764	50415438	50415590
ENSE00000954765	50415724	50415826
ENSE00001116511	50408785	50408901
ENSE00003462267	50398851	50399053
ENSE00003464625	50417045	50417097
ENSE00003478505	50402454	50402535
ENSE00003553889	50401778	50401924
ENSE00003565810	50416610	50416723
ENSE00003617684	50416396	50416528
ENSE00003692950	50417172	50417269
ENSE00003791633	50399371	50399484
ENSE00003899478	50417842	50418014
ENSE00003899951	50384347	50384390

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2828 / max 345.0804, expressed in 1786 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177145	20.3128	1775
177144	0.9701	516

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	93.72	gold quality
ventricular zone	UBERON:0003053	92.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.77	gold quality
granulocyte	CL:0000094	90.53	gold quality
lower esophagus mucosa	UBERON:0035834	90.14	gold quality
spleen	UBERON:0002106	89.34	gold quality
ganglionic eminence	UBERON:0004023	88.35	gold quality
right lobe of thyroid gland	UBERON:0001119	87.74	gold quality
left testis	UBERON:0004533	87.44	gold quality
right testis	UBERON:0004534	87.38	gold quality
left lobe of thyroid gland	UBERON:0001120	86.81	gold quality
bone marrow	UBERON:0002371	86.77	gold quality
testis	UBERON:0000473	86.54	gold quality
thyroid gland	UBERON:0002046	86.13	gold quality
esophagus mucosa	UBERON:0002469	85.96	gold quality
apex of heart	UBERON:0002098	85.88	gold quality
upper lobe of left lung	UBERON:0008952	85.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.60	gold quality
lymph node	UBERON:0000029	85.40	gold quality
transverse colon	UBERON:0001157	85.31	gold quality
blood	UBERON:0000178	85.29	gold quality
small intestine	UBERON:0002108	84.74	gold quality
right uterine tube	UBERON:0001302	84.63	gold quality
body of uterus	UBERON:0009853	84.55	gold quality
bone marrow cell	CL:0002092	84.54	gold quality
vermiform appendix	UBERON:0001154	84.47	gold quality
right lung	UBERON:0002167	84.27	gold quality
esophagus	UBERON:0001043	84.10	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.08	gold quality
colon	UBERON:0001155	83.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, E2F1, E2F4, ETS1, PARP1, SP1, SP2, SP3, TP53

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Repair of clustered DNA lesions (PMID:11923315)
• POLD1 gene mutations are not responsible for the elevated HPRT mutation rates in a colon cancer cell line (PMID:14767555)
• ubiquitin and ubiquitin-like proteins modify the p66 and p12 subunits of DNA polymerase delta (PMID:16934752)
• Abasic sites can also affect the strand displacement activity of the lagging strand DNA pol delta that can be overcome through a polymerase switch, involving the combined physical and functional interaction of DNA pol beta and Flap endonuclease 1. (PMID:19329428)
• Results suggest that the CDE/CHR-like sequence is an active functional element in the POLD1 promoter, which is important for the cell cycle regulation of the POLD1 gene. (PMID:19557333)
• Coronavirus nsp13 and DNA polymerase delta induced DNA replication stress in IBV-infected cells. (PMID:21918226)
• Pol switches at replication-blocking lesions occur by the exchange of the Pol delta and Pol zeta catalytic subunits on a preassembled complex of accessory proteins retained on DNA during translesion DNA synthesis. (PMID:22465957)
• reducing expression of individual PRMT7 target DNA repair genes showed that only the catalytic subunit of DNA polymerase, POLD1, was able to resensitize PRMT7 knock-down cells to DNA-damaging agents. (PMID:22761421)
• Pol epsilon and Pol alpha/delta seem to pursue their functions at least in part independently in late S phase (PMID:22887995)
• the down-regulations of DNA pol delta1 are age-related and have little bearing on diseases and nutritures. DNA pol delta1 has great potential for a new biomarker of aging. (PMID:22915169)
• the human lagging strand DNA polymerase delta holoenzyme is distributive (PMID:22942285)
• Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. (PMID:23263490)
• Germline and somatic polymerase epsilon and delta mutations define a new class of hypermutated colorectal and endometrial cancers. (PMID:23447401)
• POLE and POLD1 mutations are associated with endometrial cancer. (PMID:23528559)
• coordinated processing of 3’-slipped (CAG)n/(CTG)n hairpins by polymerases delta and beta on during DNA synthesis induces CAG/CTG repeat expansions. (PMID:23585564)
• a single-codon deletion in POLD1 affecting the polymerase active site causes a markedly different phenotype that includes lipodystrophy. (PMID:23770608)
• POLE and POLD1 mutations explain a fraction of familial CRC and polyposis. Sequencing the proofreading domains of POLE and POLD1 should be considered in routine genetic diagnostics. (PMID:24501277)
• Germline mutations in the proofreading domains of 2 DNA polymerases (POLE and POLD1) have been associated with a dominantly inherited, highly penetrant syndrome of oligo adenomatous polyposis and early-age-of-diagnosis colorectal and endometrial cancer. (PMID:24509466)
• analysis of phenotype of variants of the essential replicative polymerase-delta carrying missense mutations in its active site (PMID:25241845)
• None of the 1188 patients carried the POLD1 p.(Ser478Asn) variant. POLE germline variant carriers are also associated with a microsatellite instable colorectal cancer (PMID:25370038)
• POLD1 plays important role in the regulation of cell cycle progression and DNA damage repair (PMID:26087769)
• study of complete exonuclease domains of POLE and POLD1 in 529 families characterized by presence of familial or early-onset mismatch repair proficient colorectal cancer, and/or APC-negative and MUTYH-negative polyposis; results widen the phenotypic spectrum of the POLE/POLD1-associated syndrome and identify novel pathogenic variants (PMID:26133394)
• POLD1 germline mutations can result in a variably expressed and probably underdiagnosed segmental progeroid syndrome. (PMID:26172944)
• On the sequence, Escherichia coli oriC plasmid DNA, it was found hPold replicates DNA across the CCG repeats but hPole stalls at the CCG repeats even if the secondary structure is eliminated by a single stranded binding protein. (PMID:26271349)
• Germline or somatic variants in the POLE/POLD1 were identified in unresolved suspected Lynch syndrome cancers with mismatch repair defect. (PMID:26648449)
• Mutations in POLE and POLD1 in south east Asia women with grade 3 endometrioid endometrial carcinomas are associated with improved recurrence free survival. (PMID:26748215)
• Inactivating POLD1 mutations are associated with colorectal cancer. (PMID:26755646)
• POLD1 is a central mediator of DNA replication and repair, and it is implied in cancer and other pathologies. (Review) (PMID:27320729)
• WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase delta progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage. (PMID:27849570)
• findings demonstrate a key role of POLD1 and POLD3 in genome stability and S-phase progression revealing RNA-DNA hybrids-dependent effects for POLD3 that might be partly due to its Pol zeta interaction. (PMID:27974823)
• Frameshift mutation in POLD1 gene is associated with mismatch repair-deficiency and Lynch syndrome. (PMID:28218421)
• To our knowledge, the four Valencian families included in the present study are the only families where the POLD1 Leu474Pro mutation has been found. (PMID:28306219)
• the pathogenic role of the POLD1-R689W mutation in the development of the human tumor and emphasize the need to experimentally determine the significance of Poldelta variants present in sporadic tumors. (PMID:28368425)
• Mutation in DNA Polymerase III gene is associated with MMR deficiency in cancer. (PMID:28512192)
• Our work highlights that mutations in different POLD1 domains can lead to phenotypic variability, ranging from dominantly inherited cancer predisposition syndromes, to mild MDPL phenotypes (PMID:28521875)
• POLH & POLK are both able to exchange with PolD1 stalled at repetitive CFS (common fragile sites) sequences. POLD1 synthesis was inhibited by replication stress caused by aphidicolin, preventing any replication past CFS. Importantly, POLH & POLK were still proficient in rescuing this stalled POLD1 synthesis. POLD1 stalling at CFSs allows for free exchange with specialized polymerase that is not driven by PCNA. (PMID:28605669)
• DNA polymerase delta catalytic subunit controls noncentrosomal gammaTuRC activity and regulates the organization of Golgi-derived microtubules. (PMID:28916777)
• The proofreading activity of DNA polymerase delta plays a role in shunting DNA mismatch repair to an EXO1-dependent excision pathway as opposed to directly participating in gap formation via its 3’-5’ exonuclease activity. (PMID:28934474)
• We demonstrated an association between six previously published single nucleotide polymorphisms (rs15869 [ BRCA2], rs1805389 [ LIG4], rs8079544 [ TP53], rs25489 [ XRCC1], rs1673041 [ POLD1], and rs11615 [ ERCC1]) and subsequent CNS tumors in survivors of childhood cancer treated by radiation therapy. (PMID:28976792)
• POLD1 played important roles in regulating cell cycle- and DNA replication-related pathways. E2F could upregulate the expression levels of POLD1 by deregulating the methylations of their promoters to promote the relapse of Acute Lymphoblastic Leukemia . (PMID:29768346)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pold1	ENSDARG00000027689
mus_musculus	Pold1	ENSMUSG00000038644
rattus_norvegicus	Pold1	ENSRNOG00000019681
drosophila_melanogaster	PolD1	FBGN0263600
caenorhabditis_elegans		WBGENE00008645

Paralogs (3): REV3L (ENSG00000009413), NEXMIF (ENSG00000050030), POLA1 (ENSG00000101868)

Protein

Protein identifiers

DNA polymerase delta catalytic subunit — P28340 (reviewed: P28340)

Alternative names: 3’-5’ exodeoxyribonuclease, DNA polymerase subunit delta p125

All UniProt accessions (9): P28340, A0A087WYJ2, A0A2R8Y705, A0A2R8Y7K6, M0QXE6, M0QXQ2, M0QZR8, M0R2B7, M0R2J2

UniProt curated annotations — full annotation on UniProt →

Function. As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3’- to 5’-exonuclease activities. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5’-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites.

Subunit / interactions. Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing both DNA polymerase and 3’ to 5’ proofreading exonuclease activities. Within Pol-delta4, directly interacts with POLD2 and POLD4. Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites. POLD1 displays different catalytic properties depending upon the complex it is found in. It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage. Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity. As POLD2 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity. Also observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2. Interacts with CIAO1. Interacts with POLDIP2. Interacts with RFC1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, with high levels of expression in heart and lung.

Disease relevance. Colorectal cancer 10 (CRCS10) [MIM:612591] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Disease susceptibility is associated with variants affecting the gene represented in this entry. Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) [MIM:615381] An autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, metabolic abnormalities including insulin resistance and diabetes mellitus, sclerodermatous skin, and a facial appearance characterized by mandibular hypoplasia. Sensorineural deafness occurs late in the first or second decades of life. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 120 (IMD120) [MIM:620836] An autosomal recessive immunologic disorder manifesting in early childhood with recurrent upper and lower respiratory tract infections, lymphopenia, and hypogammaglobulinemia. Affected individuals may also develop persistent viral infections, particularly of the herpes family. Additional variable features include hearing loss, speech delay, short stature, and mildly impaired intellectual development. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation. Stimulated in the presence of PCNA. This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2.

Cofactor. Binds 1 [4Fe-4S] cluster.

Domain organisation. The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.

Induction. Up-regulated by serum stimulation.

Similarity. Belongs to the DNA polymerase type-B family.

RefSeq proteins (3): NP_001243778, NP_001295561, NP_002682* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006133	DNA-dir_DNA_pol_B_exonuc	Domain
IPR006134	DNA-dir_DNA_pol_B_multi_dom	Domain
IPR006172	DNA-dir_DNA_pol_B	Family
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR017964	DNA-dir_DNA_pol_B_CS	Conserved_site
IPR023211	DNA_pol_palm_dom_sf	Homologous_superfamily
IPR025687	Znf-C4pol	Domain
IPR036397	RNaseH_sf	Homologous_superfamily
IPR042087	DNA_pol_B_thumb	Homologous_superfamily
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR050240	DNA_pol_type-B	Family
IPR056435	DPOD/Z_N	Domain

Pfam: PF00136, PF03104, PF14260, PF24055

Enzyme classification (BRENDA):

• EC 2.7.7.7 — DNA-directed DNA polymerase (BRENDA: 139 organisms, 372 substrates, 325 inhibitors, 281 Km, 239 kcat entries)

Substrate kinetics (BRENDA)

52 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DATP	0.0003–3.2	52
DCTP	0.0001–2.5	46
DTTP	0.0003–47.4	46
DGTP	0.0002–2.5	29
DEOXYNUCLEOSIDE TRIPHOSPHATE	0.0012–0.64	12
DNAN	—	7
7-DEAZA-2’-DEOXYADENOSINE 5’-TRIPHOSPHATE	0.0011–0.344	5
N1-METHYL-2’-DEOXYADENOSINE 5’-TRIPHOSPHATE	0.223–0.403	5
2-AMINOPURINE-2’-DEOXY-D-RIBOSE 5’-TRIPHOSPHATE	0.006–0.0144	2
2-THIO-DCTP	0.067–0.98	2
5-METHYL-DCTP	0.013–1.22	2
DAMP:DG	1.153–1.42	2
DCMP:DG	—	2
DGMP:DG	0.263–0.3511	2
DTMP:DG	1.26–1.43	2

Catalyzed reactions (Rhea), 1 shown:

• DNA(n) + a 2’-deoxyribonucleoside 5’-triphosphate = DNA(n+1) + diphosphate (RHEA:22508)

UniProt features (132 total): strand 42, helix 32, sequence variant 22, turn 16, binding site 8, mutagenesis site 3, short sequence motif 2, sequence conflict 2, chain 1, zinc finger region 1, modified residue 1, cross-link 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6TNY	ELECTRON MICROSCOPY	3.08
9EKB	ELECTRON MICROSCOPY	3.65
6TNZ	ELECTRON MICROSCOPY	4.05
6S1M	ELECTRON MICROSCOPY	4.27
6S1N	ELECTRON MICROSCOPY	4.86
6S1O	ELECTRON MICROSCOPY	8.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28340-F1	86.93	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 1061; 1071; 1076; 1012; 1015; 1026; 1029; 1058

Post-translational modifications (2): 19, 574

Mutagenesis-validated functional residues (3):

Position	Phenotype
402	loss of exonuclease activity. no effect on dna polymerase activity.
602	loss of polymerase activity; when associated with a-757.
757	loss of polymerase activity; when associated with a-602.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-174411	Polymerase switching on the C-strand of the telomere
R-HSA-174414	Processive synthesis on the C-strand of the telomere
R-HSA-174417	Telomere C-strand (Lagging Strand) Synthesis
R-HSA-174437	Removal of the Flap Intermediate from the C-strand
R-HSA-2564830	Cytosolic iron-sulfur cluster assembly
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-69091	Polymerase switching
R-HSA-69166	Removal of the Flap Intermediate
R-HSA-69183	Processive synthesis on the lagging strand

MSigDB gene sets: 588 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, E2F_Q4, KALMA_E2F1_TARGETS, REACTOME_DNA_REPLICATION, HORIUCHI_WTAP_TARGETS_DN, E2F4DP1_01, GOBP_CELLULAR_RESPONSE_TO_UV, GOMF_NUCLEASE_ACTIVITY, CROONQUIST_NRAS_SIGNALING_DN, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_DNA_DAMAGE_TOLERANCE, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (13): DNA synthesis involved in DNA repair (GO:0000731), DNA replication (GO:0006260), DNA-templated DNA replication (GO:0006261), DNA repair (GO:0006281), base-excision repair, gap-filling (GO:0006287), nucleotide-excision repair, DNA gap filling (GO:0006297), response to UV (GO:0009411), cellular response to UV (GO:0034644), DNA replication proofreading (GO:0045004), fatty acid homeostasis (GO:0055089), error-free translesion synthesis (GO:0070987), DNA biosynthetic process (GO:0071897), DNA damage response (GO:0006974)

GO Molecular Function (20): nucleotide binding (GO:0000166), DNA binding (GO:0003677), chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), DNA-directed DNA polymerase activity (GO:0003887), zinc ion binding (GO:0008270), 3’-5’-DNA exonuclease activity (GO:0008296), enzyme binding (GO:0019899), 4 iron, 4 sulfur cluster binding (GO:0051539), nucleic acid binding (GO:0003676), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), 3’-5’ exonuclease activity (GO:0008408), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), hydrolase activity (GO:0016787), DNA polymerase activity (GO:0034061), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (8): nucleotide-excision repair complex (GO:0000109), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), aggresome (GO:0016235), delta DNA polymerase complex (GO:0043625), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Telomere C-strand (Lagging Strand) Synthesis	2
Mismatch Repair	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	2
Lagging Strand Synthesis	2
DNA Damage Bypass	1
Extension of Telomeres	1
Processive synthesis on the C-strand of the telomere	1
Metabolism	1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Leading Strand Synthesis	1
Processive synthesis on the lagging strand	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	5
DNA biosynthetic process	3
binding	3
cellular anatomical structure	3
DNA repair	2
catalytic activity	2
nuclear protein-containing complex	2
DNA replication	1
DNA damage response	1
base-excision repair	1
nucleotide-excision repair	1
response to light stimulus	1
response to UV	1
cellular response to light stimulus	1
DNA-templated DNA replication maintenance of fidelity	1
lipid homeostasis	1
translesion synthesis	1
nucleic acid biosynthetic process	1
cellular response to stress	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
DNA binding	1
DNA polymerase activity	1
transition metal ion binding	1
3’-5’ exonuclease activity	1
DNA exonuclease activity, producing 5’-phosphomonoesters	1
protein binding	1
iron-sulfur cluster binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
exonuclease activity	1
transferase activity, transferring phosphorus-containing groups	1
nucleotidyltransferase activity	1
catalytic activity, acting on DNA	1
cation binding	1
metal cluster binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

3359 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLD1	POLD2	P49005	999
POLD1	POLD3	Q15054	998
POLD1	POLE	Q07864	988
POLD1	POLD4	Q9HCU8	980
POLD1	PMS2	P54278	872
POLD1	MUTYH	Q9UIF7	868
POLD1	FEN1	P39748	856
POLD1	MSH6	P52701	840
POLD1	POLE2	P56282	819
POLD1	EXO1	Q9UQ84	814
POLD1	MSH2	P43246	811
POLD1	WRN	Q14191	794
POLD1	MLH3	P49751	793
POLD1	MLH1	P40692	790
POLD1	LIG1	P18858	778

IntAct

205 interactions, top by confidence:

A	B	Type	Score
CIAO2B	CIAO1	psi-mi:“MI:0915”(physical association)	0.950
POLD1	POLD2	psi-mi:“MI:0914”(association)	0.910
MMS19	CIAO1	psi-mi:“MI:0915”(physical association)	0.910
MMS19	CIAO1	psi-mi:“MI:0914”(association)	0.910
POLD2	POLD1	psi-mi:“MI:0407”(direct interaction)	0.910
POLD1	POLD2	psi-mi:“MI:0407”(direct interaction)	0.910
POLD2	POLD1	psi-mi:“MI:0914”(association)	0.910
POLD1	POLD2	psi-mi:“MI:0915”(physical association)	0.910
POLD2	POLD1	psi-mi:“MI:0915”(physical association)	0.910
POLD4	POLD1	psi-mi:“MI:0915”(physical association)	0.900
POLD4	POLD1	psi-mi:“MI:0407”(direct interaction)	0.900
POLD1	POLD4	psi-mi:“MI:0407”(direct interaction)	0.900
POLD4	POLD1	psi-mi:“MI:0914”(association)	0.900
POLD3	POLD1	psi-mi:“MI:0914”(association)	0.900
POLD1	POLD4	psi-mi:“MI:0915”(physical association)	0.900
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MMS19	ERCC2	psi-mi:“MI:0914”(association)	0.690
PCNA	POLD1	psi-mi:“MI:0914”(association)	0.670
PCNA	POLD1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (436): POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-Western), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD2 (Co-fractionation), PPP2R5C (Co-fractionation), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD1 (Affinity Capture-MS), POLD2 (Affinity Capture-MS), POLD3 (Affinity Capture-MS)

ESM2 similar proteins: A0MTA1, A1YES6, A1YFZ3, A2T6Y4, A2T7I6, A5WVX1, B4FAT0, O54747, O94903, P0A2X3, P0A2X4, P13051, P23196, P26882, P27695, P28339, P28340, P28352, P36776, P43138, P52431, P97283, P97931, Q08752, Q08DF7, Q0J705, Q0V9S0, Q16775, Q32LH4, Q3B7M2, Q3T0G5, Q3TIU4, Q4P1V1, Q4R5U5, Q4R6C1, Q59HJ6, Q5R4Z1, Q5XIP6, Q5ZI23, Q653S9

Diamond homologs: O36363, O54747, O71121, P03198, P04292, P04293, P07917, P07918, P08546, P09252, P09854, P15436, P24907, P27172, P28339, P28340, P28857, P28858, P30315, P30316, P46588, P52342, P52367, P52431, P54358, P89453, P90829, P97283, Q1HVC1, Q2HRD0, Q3KSP1, Q4JQU7, Q54N97, Q69025, Q6S6P1, Q6SW77, Q6UDK1, Q85428, Q9DKT8, Q9E6N9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLD1	“form complex”	“DNA polymerase delta”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 185 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Removal of the Flap Intermediate from the C-strand	6	30.4×	1e-05
Processive synthesis on the C-strand of the telomere	5	30.4×	5e-05
Telomere C-strand (Lagging Strand) Synthesis	5	30.4×	5e-05
PCNA-Dependent Long Patch Base Excision Repair	5	20.8×	2e-04
Recognition of DNA damage by PCNA-containing replication complex	6	18.3×	6e-05
Gap-filling DNA repair synthesis and ligation in GG-NER	5	17.6×	5e-04
Polymerase switching on the C-strand of the telomere	5	16.9×	5e-04
Termination of translesion DNA synthesis	6	16.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	10	17.9×	3e-07
DNA-templated DNA replication	5	17.3×	3e-03
intrinsic apoptotic signaling pathway	6	13.3×	2e-03
epidermal growth factor receptor signaling pathway	8	12.2×	2e-04
cellular response to UV	6	10.9×	4e-03
chromosome segregation	7	7.5×	6e-03
DNA damage response	13	4.3×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — BRCA, ESCA.

Clinical variants and AI predictions

ClinVar

5828 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	2948
Likely benign	2000
Benign	103

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1077091	NM_002691.4(POLD1):c.3148del (p.Arg1050fs)	Pathogenic
4682116	NM_002691.4(POLD1):c.365_377del (p.Val122fs)	Pathogenic
60775	NM_002691.4(POLD1):c.1809CTC[1] (p.Ser605del)	Pathogenic
1065532	NM_002691.4(POLD1):c.3219C>G (p.Ser1073Arg)	Likely pathogenic
239243	NM_002691.4(POLD1):c.1519C>T (p.Arg507Cys)	Likely pathogenic
4082309	NM_002691.4(POLD1):c.1432A>C (p.Ser478Arg)	Likely pathogenic

SpliceAI

4826 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50399481:GTGG:G	donor_gain	1.0000
19:50399483:GG:G	donor_gain	1.0000
19:50399484:GG:G	donor_gain	1.0000
19:50402121:GAGA:G	donor_gain	1.0000
19:50402122:AGAG:A	donor_loss	1.0000
19:50402123:GA:G	donor_gain	1.0000
19:50402124:AGT:A	donor_loss	1.0000
19:50402125:G:GG	donor_gain	1.0000
19:50402125:GTG:G	donor_loss	1.0000
19:50402199:CCACA:C	acceptor_loss	1.0000
19:50402200:CACA:C	acceptor_loss	1.0000
19:50402201:ACAGG:A	acceptor_loss	1.0000
19:50402202:CAGG:C	acceptor_loss	1.0000
19:50402203:AGGC:A	acceptor_loss	1.0000
19:50402204:G:GT	acceptor_loss	1.0000
19:50402204:GGCAT:G	acceptor_gain	1.0000
19:50402374:G:GA	donor_loss	1.0000
19:50402374:G:GG	donor_gain	1.0000
19:50402375:T:A	donor_loss	1.0000
19:50402737:CAAAG:C	donor_loss	1.0000
19:50402738:AAAG:A	donor_loss	1.0000
19:50403205:G:GT	donor_gain	1.0000
19:50403217:CAG:C	donor_loss	1.0000
19:50403219:GG:G	donor_loss	1.0000
19:50403485:A:AG	acceptor_gain	1.0000
19:50403486:C:G	acceptor_gain	1.0000
19:50403488:CCCAG:C	acceptor_loss	1.0000
19:50403489:CCAG:C	acceptor_loss	1.0000
19:50403490:CA:C	acceptor_loss	1.0000
19:50403491:A:AC	acceptor_loss	1.0000

AlphaMissense

7142 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50402711:A:C	S314R	1.000
19:50402713:C:A	S314R	1.000
19:50402713:C:G	S314R	1.000
19:50402718:A:T	D316V	1.000
19:50402725:G:C	E318D	1.000
19:50402725:G:T	E318D	1.000
19:50402728:C:G	C319W	1.000
19:50403058:T:C	F326L	1.000
19:50403060:C:A	F326L	1.000
19:50403060:C:G	F326L	1.000
19:50403083:T:A	V334D	1.000
19:50403556:T:C	F401L	1.000
19:50403558:C:A	F401L	1.000
19:50403558:C:G	F401L	1.000
19:50406444:T:A	L474H	1.000
19:50406444:T:C	L474P	1.000
19:50406455:A:C	S478R	1.000
19:50406457:C:A	S478R	1.000
19:50406457:C:G	S478R	1.000
19:50406479:A:G	K486E	1.000
19:50406481:G:C	K486N	1.000
19:50406481:G:T	K486N	1.000
19:50406504:T:A	I494N	1.000
19:50406513:T:C	L497P	1.000
19:50407011:T:A	L508Q	1.000
19:50407011:T:C	L508P	1.000
19:50407019:T:C	Y511H	1.000
19:50407022:T:C	C512R	1.000
19:50407023:G:A	C512Y	1.000
19:50407024:C:G	C512W	1.000

dbSNP variants (sampled 300 via entrez): RS1000004716 (19:50394860 A>C), RS1000042420 (19:50384553 G>A,T), RS1000129569 (19:50409361 A>G), RS1000144461 (19:50396551 C>A,G,T), RS1000199387 (19:50405656 G>A,T), RS1000388561 (19:50418396 G>A), RS1000425242 (19:50414437 G>A,T), RS1000463712 (19:50398444 C>T), RS1000646313 (19:50383858 G>C), RS1000680428 (19:50403667 T>C), RS1000748730 (19:50404507 C>G,T), RS1000784700 (19:50404735 C>T), RS1000835158 (19:50414492 A>C), RS1000911565 (19:50383741 T>A,C), RS1000913420 (19:50418083 C>T)

Disease associations

OMIM: gene MIM:174761 | disease phenotypes: MIM:612591, MIM:615381, MIM:620836, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
mandibular hypoplasia-deafness-progeroid syndrome	Definitive	Autosomal dominant
POLD1-related polyposis and colorectal cancer syndrome	Definitive	Autosomal dominant
colorectal cancer, susceptibility to, 10	Strong	Autosomal dominant
immunodeficiency 120	Strong	Autosomal recessive
Polymerase proofreading-related adenomatous polyposis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
non-severe combined immunodeficiency due to polymerase delta deficiency	Limited	AR
POLD1-related polyposis and colorectal cancer syndrome	Definitive	AD
mandibular hypoplasia-deafness-progeroid syndrome	Definitive	AD

Mondo (20): colorectal cancer, susceptibility to, 10 (MONDO:0012953), hereditary neoplastic syndrome (MONDO:0015356), colon carcinoma (MONDO:0002032), familial colorectal cancer type X (MONDO:0018604), Polymerase proofreading-related adenomatous polyposis (MONDO:0018653), mandibular hypoplasia-deafness-progeroid syndrome (MONDO:0014157), immunodeficiency 120 (MONDO:0970994), intellectual disability (MONDO:0001071), exocrine pancreatic carcinoma (MONDO:0005192), familial colorectal cancer (MONDO:0023113), breast cancer (MONDO:0007254), endometrial carcinoma (MONDO:0002447), familial ovarian cancer (MONDO:0016248), malignant colon neoplasm (MONDO:0021063), colorectal cancer (MONDO:0005575)

Orphanet (11): Inherited cancer-predisposing syndrome (Orphanet:140162), Attenuated familial adenomatous polyposis (Orphanet:220460), Familial colorectal cancer Type X (Orphanet:440437), Polymerase proofreading-related polyposis (Orphanet:447877), Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome (Orphanet:363649), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074), Combined T and B cell immunodeficiency (Orphanet:101972), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), OBSOLETE: Familial ovarian cancer (Orphanet:213517), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000252	Microcephaly
HP:0000320	Bird-like facies
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000444	Convex nasal ridge
HP:0000505	Visual impairment
HP:0000520	Proptosis
HP:0000678	Dental crowding
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000819	Diabetes mellitus
HP:0000855	Insulin resistance
HP:0000939	Osteoporosis
HP:0001123	Visual field defect
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001371	Flexion contracture
HP:0001397	Hepatic steatosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_610	Obesity-related traits	6.000000e-06
GCST009268_6	Dental caries (decayed, missing and filled tooth surfaces)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005190	urinary nitrogen measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363042 (PROTEIN FAMILY), CHEMBL2735 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
POLD1 C284Y	Pembrolizumab	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID4776
POLD1 E374K	Pembrolizumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID4777

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 4 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.64	IC50	2300	nM	ZIDOVUDINE TRIPHOSPHATE

PubChem BioAssay actives

1 with measured affinity, of 26 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	255107: Inhibition of human delta DNA polymerase (95 uL) activity in a solution containg 6.4 mM HEPES (pH 7.5) upon incubation for 12 minutes at 26 degrees C with the compound dissolved in DMSO	ic50	2.3000	uM

CTD chemical–gene interactions

62 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases expression	5
bisphenol A	decreases expression	2
Arsenic Trioxide	affects binding, decreases reaction, increases expression	2
Copper	increases expression, affects binding, decreases expression	2
Hydrogen Peroxide	decreases expression	2
Particulate Matter	decreases expression	2
TAK-243	increases sumoylation	1
1,12-benzoperylene	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CPG-oligonucleotide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
LDN 193189	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2013620	Binding	Inhibition of human DNA polymerase delta assessed as inhibition of incorporation of dTTP into poly(dA)/oligo(dT)18 after 60 mins	Pinophilins A and B, inhibitors of mammalian A-, B-, and Y-family DNA polymerases and human cancer cell proliferation. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7XZ	Ubigene A-549 POLD1 KO	Cancer cell line	Male
CVCL_VK11	587X	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01169220	PHASE4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	PHASE4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	PHASE4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	PHASE4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	PHASE4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	PHASE4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	PHASE4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	PHASE4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	PHASE4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT00002968	PHASE3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	PHASE3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	PHASE3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	PHASE3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	PHASE3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
NCT00070122	PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	PHASE3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	PHASE3	COMPLETED	Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II or Stage III Colon Cancer
NCT00188305	PHASE3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	PHASE3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	PHASE3	ACTIVE_NOT_RECRUITING	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	PHASE3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	PHASE3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	PHASE3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	PHASE3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	PHASE3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	PHASE3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	PHASE3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	PHASE3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	PHASE3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	PHASE3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00756977	PHASE3	COMPLETED	BLI850 vs an Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00894725	PHASE3	COMPLETED	Laparoscopic Versus Open Left Colonic Resection
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study