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): 5,905 total — 3 pathogenic, 3 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 4 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 110
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.88 (unconstrained)
• MANE Select transcript: NM_002691
• Interaction hub: 2,375 STRING partners (top 5% of genes corpus-wide)

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: 57 — 39 protein_coding, 14 nonsense_mediated_decay, 4 retained_intron

MANE Select: ENST00000440232

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 1, TSL 5: 6

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, ENST00000989623, ENST00000989624, ENST00001009934, ENST00001009935, ENST00001009937, ENST00001089081, ENST00001089082, ENST00001089083, ENST00001089084, ENST00001089086, ENST00001089087, ENST00001089088, ENST00001141211

RefSeq mRNA: 7 — MANE Select: NM_002691 NM_001256849, NM_001308632, NM_001438210, NM_001438211, NM_001438212, NM_001438213, 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.

Highest expression (Bgee): mucosa of transverse colon, ventricular zone, primordial germ cell in gonad, granulocyte, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

POLD1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	5.3e-08	+0.46	19:50388122:G:A
Esophagus Mucosa	eqtl	1.7e-02	-0.24	19:49749337:T:C
Minor Salivary Gland	eqtl	2.2e-02	-0.25	19:50253993:G:A
Cells Cultured fibroblasts	eqtl	4.8e-02	-0.22	19:51198493:T:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 134 tissues 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
metanephros cortex	UBERON:0010533	83.77	gold quality
skin of abdomen	UBERON:0001416	83.69	gold quality
right ovary	UBERON:0002118	83.62	gold quality
ectocervix	UBERON:0012249	83.58	gold quality
intestine	UBERON:0000160	83.50	gold quality
myometrium	UBERON:0001296	83.47	gold quality
placenta	UBERON:0001987	83.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.25	gold quality
vagina	UBERON:0000996	83.24	gold quality
right lobe of liver	UBERON:0001114	83.18	gold quality
cerebellar hemisphere	UBERON:0002245	83.14	gold quality
cerebellum	UBERON:0002037	82.99	gold quality
cerebellar cortex	UBERON:0002129	82.94	gold quality
zone of skin	UBERON:0000014	82.91	gold quality
cortex of kidney	UBERON:0001225	82.90	gold quality
left ovary	UBERON:0002119	82.85	gold quality
minor salivary gland	UBERON:0001830	82.83	gold quality
lower esophagus	UBERON:0013473	82.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.68	gold quality
skin of leg	UBERON:0001511	82.54	gold quality
lung	UBERON:0002048	82.54	gold quality
saliva-secreting gland	UBERON:0001044	82.51	gold quality
ovary	UBERON:0000992	82.19	gold quality
endocervix	UBERON:0000458	82.14	gold quality
prostate gland	UBERON:0002367	82.12	gold quality
pituitary gland	UBERON:0000007	82.08	gold quality
omental fat pad	UBERON:0010414	82.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.96	gold quality
uterine cervix	UBERON:0000002	81.94	gold quality
right adrenal gland	UBERON:0001233	81.93	gold quality
left uterine tube	UBERON:0001303	81.89	gold quality
body of stomach	UBERON:0001161	81.85	gold quality
tibial nerve	UBERON:0001323	81.85	gold quality
fundus of stomach	UBERON:0001160	81.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.44	gold quality
right adrenal gland cortex	UBERON:0035827	81.40	gold quality
adipose tissue	UBERON:0001013	81.32	gold quality
adenohypophysis	UBERON:0002196	81.32	gold quality
body of pancreas	UBERON:0001150	81.28	gold quality
left coronary artery	UBERON:0001626	81.25	gold quality
multicellular organism	UBERON:0000468	81.24	gold quality
heart left ventricle	UBERON:0002084	81.14	gold quality
thoracic mammary gland	UBERON:0005200	80.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.88	gold quality
ascending aorta	UBERON:0001496	80.81	gold quality
thoracic aorta	UBERON:0001515	80.81	gold quality
stromal cell of endometrium	CL:0002255	80.70	gold quality
left adrenal gland cortex	UBERON:0035825	80.69	gold quality
left adrenal gland	UBERON:0001234	80.63	gold quality
stomach	UBERON:0000945	80.44	gold quality
adult mammalian kidney	UBERON:0000082	79.95	gold quality
descending thoracic aorta	UBERON:0002345	79.93	gold quality
leukocyte	CL:0000738	79.92	gold quality
cortical plate	UBERON:0005343	79.92	gold quality
heart	UBERON:0000948	79.82	gold quality
gastrocnemius	UBERON:0001388	79.72	gold quality
monocyte	CL:0000576	79.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.51	gold quality
tonsil	UBERON:0002372	79.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.39	gold quality
right atrium auricular region	UBERON:0006631	79.38	gold quality
duodenum	UBERON:0002114	79.33	gold quality
adrenal gland	UBERON:0002369	79.15	gold quality
substantia nigra	UBERON:0002038	79.06	gold quality
muscle of leg	UBERON:0001383	79.00	gold quality
tibial artery	UBERON:0007610	78.61	gold quality
popliteal artery	UBERON:0002250	78.60	gold quality
kidney	UBERON:0002113	78.41	gold quality
urinary bladder	UBERON:0001255	78.18	gold quality
liver	UBERON:0002107	77.93	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	19.2	medium
Thymus	tissue	8.2
Lymph node	tissue	7.1	high
Vagina	tissue	6.2	medium
Skin 1	tissue	5.8	high
Spleen	tissue	5.8	medium
Small intestine	tissue	5.7	high
Appendix	tissue	5.2	high
Salivary gland	tissue	4.4	high
Placenta	tissue	4.4	high
Testis	tissue	4.3	high
Corpus callosum	tissue	4.2
Duodenum	tissue	4.1	high
Choroid plexus	tissue	4.0
Cerebellum	tissue	3.9	high
Locus coeruleus	tissue	3.9
Colon	tissue	3.8	high
Tonsil	tissue	3.7	high
Pituitary gland	tissue	3.6
Stomach 1	tissue	3.6	high
Olfactory bulb	tissue	3.4
Skeletal muscle	tissue	3.3	medium
Lung	tissue	3.3	high
Hippocampus	tissue	3.3	medium
Endometrium 1	tissue	3.2	medium
Spinal cord	tissue	3.2
Nucleus accumbens	tissue	3.1
Medulla oblongata	tissue	3.0
Ovary	tissue	2.9	high
Amygdala	tissue	2.9
Hippocampal formation	tissue	2.9
Midbrain	tissue	2.8
Substantia nigra	tissue	2.8
Cerebral cortex	tissue	2.7	medium
Basal ganglia	tissue	2.7	medium
Superior colliculi	tissue	2.7
Insular cortex	tissue	2.7
Putamen	tissue	2.6
Ventral forebrain	tissue	2.6
Periaqueductal gray	tissue	2.6
Retrosplenial cortex	tissue	2.6
Temporal cortex	tissue	2.6
Adipose tissue	tissue	2.5	low
Esophagus	tissue	2.5	high
Thalamus	tissue	2.5
Hypothalamus	tissue	2.5
Retrosplenial and cingulate cortex	tissue	2.5
Septum	tissue	2.5
Somatosensory cortex	tissue	2.5
Occipital cortex	tissue	2.5
Pons	tissue	2.4
Postcentral gyrus	tissue	2.4
Entorhinal cortex	tissue	2.4
Prefrontal cortex	tissue	2.3
Motor cortex	tissue	2.3
Caudate putamen	tissue	2.3
Seminal vesicle	tissue	2.1	medium
Adrenal gland	tissue	2.0	medium
Fallopian tube	tissue	2.0	high
Parathyroid gland	tissue	1.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Nucleus ambiguus (6.8), Nucleus raphe pallidus (6.5), Nucleus rhomboideus (5.7), Anterior thalamic nucleus, ventral (5.6), Area striata (white matter) (5.4).

Regulation

Is transcription factor: no

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

Functional genomics

gnomAD constraint: pLI 8e-19, LOEUF 0.878, missense Z 1.4 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000440232 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:50,398,852–50,402,277	332 / 315.7	1.05	no
19:50,402,278–50,415,755	720 / 1002.6	0.72	no
19:50,415,756–50,417,944	286 / 277.5	1.03	no
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.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): LN-428 (-3.385), TYK-nu (-3.186), SNU-1079 (-3.032), LN382 (-3.0), JM1 (-2.999), OCI-LY-19 (-2.972), T84 (-2.97), RH-41 (-2.933), HCC38 (-2.9), D283 Med (-2.883), OCI-AML3 (-2.862), A-673 (-2.857), CL-11 (-2.821), CAL-29 (-2.814), SK-N-DZ (-2.814).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97741) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 25 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased tumor incidence	4
premature death	4
increased lymphoma incidence	3
increased T cell derived lymphoma incidence	2
increased skin tumor incidence	2
embryonic lethality between implantation and somite formation, complete penetrance	2
decreased cell proliferation	1
enlarged thymus	1
decreased embryo size	1
abnormal allantois morphology	1
increased lung adenocarcinoma incidence	1
increased sarcoma incidence	1
abnormal embryonic tissue morphology	1
increased intestinal adenoma incidence	1
increased intestinal adenocarcinoma incidence	1
increased squamous cell carcinoma incidence	1
inner cell mass degeneration	1
abnormal trophoblast layer morphology	1
cardiomyopathy	1
increased lung tumor incidence	1
embryonic lethality between somite formation and embryo turning, complete penetrance	1
embryonic lethality during organogenesis, complete penetrance	1
absent inner cell mass proliferation	1
abnormal primitive streak elongation	1
increased embryonic tissue cell apoptosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mesocricetus auratus	P97283	96.0%	Diamond
Bos taurus	P28339	93.9%	Diamond
Oryza sativa Japonica Group	Q9LRE6	85.5%	Diamond
Glycine max	O48901	84.4%	Diamond
Arabidopsis thaliana	Q9LVN7	82.9%	Diamond
Thermococcus fumicolans	P74918	68.8%	Diamond
Saccharomyces cerevisiae S288C	P15436	62.2%	Diamond
Candida albicans	P46588	62.2%	Diamond
Schizosaccharomyces pombe 972h-	P30316	60.6%	Diamond
Dictyostelium discoideum	Q54N97	55.9%	Diamond
Plasmodium falciparum K1	P30315	49.2%	Diamond
Human herpesvirus 4 strain B95-8	P03198	99.9%	Diamond
Epstein-barr virus strain ag876	Q1HVC1	99.9%	Diamond
Human herpesvirus 6 (strain Uganda-1102)	P28857	97.9%	Diamond
Human herpesvirus 6 strain Z29	Q9QJ32	97.9%	Diamond
Paramecium bursaria Chlorella virus NY2A	P30320	88.4%	Diamond
Paramecium bursaria Chlorella virus 1	P30321	88.4%	Diamond
Herpesvirus saimiri (strain 11)	P24907	61.2%	Diamond
Human herpesvirus 8 strain GK18	Q2HRD0	61.2%	Diamond
Equid herpesvirus type 2 strain 86/87	P52367	59.2%	Diamond
macacine betaherpesvirus 3	O71121	59.1%	Diamond
Alcelaphine herpesvirus 1 strain C500	O36363	56.9%	Diamond
Guinea pig cytomegalovirus (strain 22122 / ATCC VR682) (GPCMV)	Q69025	52.3%	Diamond
Red seabream iridovirus	O70736	35.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
IZUMO2	protein-coding	126123
KCNC3	protein-coding	3748
NR1H2	protein-coding	7376
MYH14	protein-coding	79784
NAPSA	protein-coding	9476
SPIB	protein-coding	6689
MYBPC2	protein-coding	4606
GARIN5A	protein-coding	112703
EMC10	protein-coding	284361
MYREM	ncRNA	128266840

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 (7): NP_001243778, NP_001295561, NP_001425139, NP_001425140, NP_001425141, NP_001425142, 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)

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

UniProt features (134 total): strand 42, helix 36, sequence variant 22, turn 14, 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 by resolution:

PDB	Title	Method	Resolution (Å)
6TNY	Processive human polymerase delta holoenzyme	ELECTRON MICROSCOPY	3.08
9EKB	Cryo-EM structure of apo-form human DNA polymerase delta	ELECTRON MICROSCOPY	3.65
6TNZ	Human polymerase delta-FEN1-PCNA toolbelt	ELECTRON MICROSCOPY	4.05
6S1M	Human polymerase delta holoenzyme Conformer 1	ELECTRON MICROSCOPY	4.27
6S1N	Human polymerase delta holoenzyme Conformer 2	ELECTRON MICROSCOPY	4.86
6S1O	Human polymerase delta holoenzyme Conformer 3	ELECTRON MICROSCOPY	8.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
1061	[4Fe-4S] cluster
1071	[4Fe-4S] cluster
1076	[4Fe-4S] cluster
1012	Zn(2+)
1015	Zn(2+)
1026	Zn(2+)
1029	Zn(2+)
1058	[4Fe-4S] cluster

Post-translational modifications (2)

Type	Positions
Omega-n-methylarginine	19
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	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

0 curated (TAS) of 43; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

43 pathways:

ID	Pathway	Evidence
R-HSA-73884	Base Excision Repair	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-73886	Chromosome Maintenance	—
R-HSA-2564830	Cytosolic iron-sulfur cluster assembly	—
R-HSA-73893	DNA Damage Bypass	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-69306	DNA Replication	—
R-HSA-69190	DNA strand elongation	—
R-HSA-5696400	Dual Incision in GG-NER	—
R-HSA-6782135	Dual incision in TC-NER	—
R-HSA-180786	Extension of Telomeres	—
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER	—
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-5685942	HDR through Homologous Recombination (HRR)	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-69186	Lagging Strand Synthesis	—
R-HSA-69109	Leading Strand Synthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-5358508	Mismatch Repair	—
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	—
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair	—
R-HSA-69091	Polymerase switching	—
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-69183	Processive synthesis on the lagging strand	—
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex	—
R-HSA-69166	Removal of the Flap Intermediate	—
R-HSA-174437	Removal of the Flap Intermediate from the C-strand	—
R-HSA-110373	Resolution of AP sites via the multiple-nucleotide patch replacement pathway	—
R-HSA-73933	Resolution of Abasic Sites (AP sites)	—
R-HSA-69242	S Phase	—
R-HSA-69239	Synthesis of DNA	—
R-HSA-174417	Telomere C-strand (Lagging Strand) Synthesis	—
R-HSA-157579	Telomere Maintenance	—
R-HSA-5656169	Termination of translesion DNA synthesis	—
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)	—
R-HSA-110313	Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	—

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 (12): 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), 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 (6): nucleotide-excision repair complex (GO:0000109), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), delta DNA polymerase complex (GO:0043625), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

15 top-level categories:

Category	Pathways
DNA Damage Bypass	2
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
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
Resolution of Abasic Sites (AP sites)	1

GO top-level categories

41 GO namespaces:

Category	Terms
DNA metabolic process	5
DNA biosynthetic process	3
binding	3
DNA repair	2
catalytic activity	2
nuclear protein-containing complex	2
cellular anatomical structure	2
DNA replication	1
DNA damage response	1
base-excision repair	1
nucleotide-excision repair	1
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
DNA polymerase complex	1
nuclear replisome	1
chromosomal region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
DNA biosynthetic process	BP	direct assay
DNA replication	BP	mutant phenotype
DNA synthesis involved in DNA repair	BP	direct assay
DNA-templated DNA replication	BP	direct assay
base-excision repair, gap-filling	BP	direct assay
error-free translesion synthesis	BP	direct assay
fatty acid homeostasis	BP	mutant phenotype
nucleotide-excision repair, DNA gap filling	BP	mutant phenotype
delta DNA polymerase complex	CC	direct assay
membrane	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleotide-excision repair complex	CC	direct assay
nucleus	CC	direct assay
DNA binding	MF	direct assay
DNA-directed DNA polymerase activity	MF	mutant phenotype
chromatin binding	MF	direct assay
damaged DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,375 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLD1	POLE	Q07864	979
POLD1	POLD2	P49005	966
POLD1	POLD3	Q15054	959
POLD1	POLD4	Q9HCU8	896
POLD1	PMS2	P54278	872
POLD1	MUTYH	Q9UIF7	861
POLD1	PCNA	P12004	856
POLD1	MSH6	P52701	831
POLD1	MSH2	P43246	822
POLD1	EXO1	Q9UQ84	802
POLD1	LIG1	P18858	784
POLD1	MLH1	P40692	777
POLD1	FEN1	P39748	771
POLD1	NTHL1	P78549	770
POLD1	MLH3	P49751	769

IntAct

Human interaction partners of POLD1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 43 partners by confidence:

Partner	Interaction type	MIscore	Records
POLD2	association	0.910	13
POLD4	physical association	0.900	7
POLD3	association	0.900	1
PCNA	association	0.670	2
SMAD4	physical association	0.600	6
ADAMTSL4	physical association	0.560	3
CYSRT1	physical association	0.560	3
KLHL12	physical association	0.560	3
LASP1	physical association	0.560	3
TERF2IP	physical association	0.510	2
WRNIP1	association	0.500	2
ABL1	physical association	0.400	1
FYN	physical association	0.400	1
GRB2	physical association	0.400	1
SRC	physical association	0.400	1
CIAO1	association	0.350	2
BAG2	association	0.350	1
GLRX3	association	0.350	1
FBXW7	proximity	0.270	4
SMARCA4	proximity	0.270	4
SPOP	proximity	0.270	4
AKT1	proximity	0.270	1
BRAF	proximity	0.270	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
TP53	proximity	0.270	1
AP3B1	physical association	0.000	1
ARF6	physical association	0.000	1
ATRX	physical association	0.000	1

BioGRID (442 interactions; top human partners by supporting records): PCNA (Affinity Capture-MS; 12 records), MYC (Affinity Capture-MS; 8 records), POLD2 (Co-fractionation; 8 records), MMS19 (Affinity Capture-MS; 6 records), CDK2 (Co-fractionation; 5 records), POLD3 (Affinity Capture-MS; 5 records), CIAO1 (Affinity Capture-Western; 4 records), FAM96B (Affinity Capture-Western; 4 records), POLD4 (Affinity Capture-MS; 4 records), RB1 (Reconstituted Complex; 4 records), ATR (Protein-peptide; 3 records), FBXW7 (Affinity Capture-MS; 3 records), RPA1 (Co-fractionation; 3 records), RPA2 (Co-fractionation; 3 records), RPA3 (Co-fractionation; 3 records)

SIGNOR signaling

1 signaling interactions:

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

Protein complexes (CORUM) (8)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

8 complexes by size:

Complex	Subunits	Members
★ RC complex, S-phase-specific	23	POLD4, POLE2, POLE4, CCNA2, CDK2, POLD2, POLD3, RFC2, POLE, RFC1, RFC5, RPA3, LIG1, PARP1, POLA1, POLD1, RFC3, RPA2, POLA2, POLE3, RFC4, RPA1, TOP1
★ DNA synthesome complex, breast cancer MCF7 cells	23	POLA2, POLD3, POLE4, PRIM1, RFC1, RPA1, PCNA, POLD4, POLE2, POLE3, RFC4, TOP1, POLA1, RFC2, RFC3, RFC5, RPA2, RPA3, TOP2A, POLD1, POLD2, POLE, PRIM2
★ DNA synthesome complex, breast cancer cells	20	POLD3, POLE4, RFC2, RFC3, POLA2, POLE3, LIG1, PARP1, PCNA, POLD2, PRIM1, PRIM2, RFC1, RFC4, POLD4, POLE, POLE2, RFC5, POLA1, POLD1
★ RC complex, G2/M-phase-specific	19	CCNB1, POLA1, POLA2, POLD2, RPA1, RPA2, CDK1, POLD3, RFC1, RFC2, RPA3, POLD1, POLD4, POLE, POLE3, PARP1, POLE2, POLE4, TOP1
★ DNA synthesome complex, leukemia cells	19	PCNA, POLD1, RFC5, TOP2A, POLD4, PRIM1, PRIM2, RFC2, RPA2, TOP1, POLD2, POLD3, RPA1, POLA1, POLA2, RFC1, RFC3, RFC4, RPA3
★ DNA synthesome core complex	14	PCNA, POLA2, POLD1, POLD2, POLD3, POLD4, PRIM2, RFC1, POLA1, PRIM1, RFC2, RFC3, RFC4, RFC5
★ DNA polymerase delta	4	POLD1, POLD2, POLD3, POLD4
★ DNA polymerase delta, trimeric form	3	POLD1, POLD2, POLD3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Processive synthesis on the C-strand of the telomere	5	105.7×	2e-07
Telomere C-strand (Lagging Strand) Synthesis	5	105.7×	2e-07
Removal of the Flap Intermediate from the C-strand	5	88.1×	4e-07
Polymerase switching on the C-strand of the telomere	5	58.7×	2e-06
Constitutive Signaling by Aberrant PI3K in Cancer	5	17.6×	2e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	16.1×	6e-05
PIP3 activates AKT signaling	6	11.1×	3e-04
RAF/MAP kinase cascade	5	8.5×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	7	41.3×	3e-07
positive regulation of ERK1 and ERK2 cascade	6	12.2×	2e-03

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for POLD1: 5,905 ClinVar records (6 pathogenic / likely pathogenic); 2 CIViC cancer variants; 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

5,905 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	2991
Likely benign	2028
Benign	100

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
60775	NM_002691.4(POLD1):c.1809CTC[1] (p.Ser605del)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
239243	NM_002691.4(POLD1):c.1519C>T (p.Arg507Cys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
4682116	NM_002691.4(POLD1):c.365_377del (p.Val122fs)	Pathogenic	criteria provided, single submitter	1
4082309	NM_002691.4(POLD1):c.1432A>C (p.Ser478Arg)	Likely pathogenic	criteria provided, single submitter	1
1077091	NM_002691.4(POLD1):c.3148del (p.Arg1050fs)	Pathogenic	no assertion criteria provided	1
1065532	NM_002691.4(POLD1):c.3219C>G (p.Ser1073Arg)	Likely pathogenic	no assertion criteria provided	2

Per-variant reference — Sugi Variant

Explore POLD1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 2,506):

Position(s)	Effect	Δscore	Sites
19:50402203	acceptor_loss	1.0000
19:50402374–50402375	donor_loss	1.0000	4
19:50402742	donor_loss	1.0000	2
19:50403220–50403221	donor_loss	1.0000	5
19:50403486	acceptor_gain	1.0000
19:50403491–50403492	acceptor_loss	1.0000	3
19:50403598–50403599	donor_loss	1.0000	5
19:50406180–50406181	acceptor_loss	1.0000	5
19:50406323–50406324	donor_loss	1.0000	4
19:50406518	donor_loss	1.0000

AlphaMissense

3,366 missense substitutions predicted likely pathogenic (of 7,142 scored), across 781 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M760	9	0.975	0.998
M535	9	0.927	0.992
M727	9	0.914	0.997
M611	9	0.856	0.999
D757	8	1.000	1.000
D515	8	0.999	1.000
D602	8	0.999	1.000
D835	8	0.999	1.000
D316	8	0.998	1.000
D755	8	0.998	1.000
D402	8	0.997	0.999
D458	8	0.996	0.999
N698	8	0.996	1.000
D332	8	0.995	0.998
F326	8	0.994	1.000
F401	8	0.994	1.000
F603	8	0.993	1.000
D1075	8	0.991	0.998
D488	8	0.990	0.999
H900	8	0.989	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	7.56e-06
Lung Adenocarcinoma (TCGA)	unfavorable	7.56e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	9.11e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.00048

Disease associations

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

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
mandibular hypoplasia-deafness-progeroid syndrome	Definitive	Autosomal dominant	7
POLD1-related polyposis and colorectal cancer syndrome	Definitive	Autosomal dominant	2
colorectal cancer, susceptibility to, 10	Strong	Autosomal dominant	3
immunodeficiency 120	Strong	Autosomal recessive	2
Polymerase proofreading-related adenomatous polyposis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

3 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Adult solid tumours for rare disease	green
COVID-19 research	green
Colorectal cancer pertinent cancer susceptibility	green
DDG2P	green
Diabetes with additional phenotypes suggestive of a monogenic aetiology	green
Familial diabetes	green
GI tract tumours	green
Inherited polyposis and early onset colorectal cancer - germline testing	green
Insulin resistance (including lipodystrophy)	green
Monogenic diabetes	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Severe insulin resistance and lipodystrophy syndromes	green
Fetal anomalies	amber

Mondo (8): intellectual disability (MONDO:0001071), exocrine pancreatic carcinoma (MONDO:0005192), POLD1-related polyposis and colorectal cancer syndrome (MONDO:0012953), hereditary neoplastic syndrome (MONDO:0015356), mandibular hypoplasia-deafness-progeroid syndrome (MONDO:0014157), immunodeficiency 120 (MONDO:0970994), (MONDO:0100351), Polymerase proofreading-related adenomatous polyposis (MONDO:0018653)

Orphanet (6): Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074), Inherited cancer-predisposing syndrome (Orphanet:140162), Attenuated familial adenomatous polyposis (Orphanet:220460), Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome (Orphanet:363649), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 110 phenotypes (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
HP:0001402	Hepatocellular carcinoma
HP:0001620	Abnormally high-pitched voice
HP:0001824	Weight loss
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002076	Migraine
HP:0002110	Bronchiectasis
HP:0002155	Hypertriglyceridemia
HP:0002167	Abnormal speech pattern
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002354	Memory impairment
HP:0002376	Developmental regression
HP:0002516	Increased intracranial pressure
HP:0002650	Scoliosis
HP:0002671	Basal cell carcinoma
HP:0002720	Decreased circulating IgA concentration
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002808	Kyphosis
HP:0002850	Decreased circulating IgM concentration
HP:0002893	Pituitary adenoma
HP:0002894	Neoplasm of the pancreas
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003002	Breast carcinoma
HP:0003006	Neuroblastoma
HP:0003401	Paresthesia
HP:0003581	Adult onset

GWAS associations

2 associations:

Study	Trait	p-value
GCST009268_11	Dental caries (decayed, missing and filled tooth surfaces)	3e-6
GCST001762_635	Obesity-related traits	6e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005190	urinary nitrogen measurement

MeSH disease descriptors

2 disease descriptors:

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, from 2 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

2 predictive associations by evidence level:

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

CIViC curated variants (2)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

C284Y (missense variant), E374K (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

3 measured of 7 human assays (17 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6,13-di(hydroxymethyl)-2,6-dimethyl-(1S,2S,5R,6R,7R,10S,12R,13R)-tetracyclo[10.3.1.01,10.02,7]hexadecane-5,13-diol (Aphidicolin)	EC50	2000 nM
Combivir	IC50	11000 nM
(PFA)dihydroxyphosphinecarboxylic acid oxide	KI	1.42e+07 nM

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	decreases expression, affects cotreatment	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 301 trials:

NCT	Phase	Status	Title
NCT01169220	Phase 4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	Phase 4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	Phase 4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	Phase 4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	Phase 4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	Phase 4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	Phase 4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	Phase 4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	Phase 4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	Phase 4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	Phase 4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	Phase 4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	Phase 4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	Phase 4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT07802847	Phase 4	NOT_YET_RECRUITING	Innovative and Cooperative Pathway Integrating Oncogeriatric, Pharmaceutical and Pharmacological Follow-up in Elderly Patients.
NCT00002968	Phase 3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	Phase 3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	Phase 3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	Phase 3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	Phase 3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	Phase 3	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	Phase 3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	Phase 3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	Phase 3	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	Phase 3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	Phase 3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	Phase 3	COMPLETED	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	Phase 3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	Phase 3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	Phase 3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	Phase 3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	Phase 3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	Phase 3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	Phase 3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	Phase 3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	Phase 3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	Phase 3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00756977	Phase 3	COMPLETED	BLI850 vs an Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00894725	Phase 3	COMPLETED	Laparoscopic Versus Open Left Colonic Resection
NCT00911170	Phase 3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01092481	Phase 3	UNKNOWN	Study Investigating the Role of Oxaliplatin Duration in Modified FOLFOX-6 or CAPOX Regimen as Adjuvant Colon Cancer Therapy
NCT01460589	Phase 3	ACTIVE_NOT_RECRUITING	Early Commencement of Adjuvant Chemotherapy for Colon Cancer
NCT01483443	Phase 3	COMPLETED	Oophorectomy Followed by Chemotherapy Versus Chemotherapy Alone in Colorectal Cancer Patients
NCT01606098	Phase 3	COMPLETED	The Role of Surgery of the Primary Tumour in Patients With Synchronous Unresectable Metastases of Colorectal Cancer
NCT01727388	Phase 3	COMPLETED	Informativeness to Digital Rectal Examination
NCT01918527	Phase 3	COMPLETED	Neoadjuvant Chemotherapy Versus Standard Treatment in Patients With Locally Advanced Colon Cancer
NCT02254486	Phase 3	COMPLETED	Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults
NCT02280278	Phase 3	UNKNOWN	Cytokine-induced Killer Cell Immunotherapy for Surgical Resected Stage III Colorectal Cancer Patients After Chemotherapy
NCT02301286	Phase 3	ACTIVE_NOT_RECRUITING	A Trial of Aspirin on Recurrence and Survival in Colon Cancer Patients
NCT02448173	Phase 3	NOT_YET_RECRUITING	A Multicenter Study of Active Specific Immunotherapy With OncoVax® in Patients With Stage II Colon Cancer
NCT02467582	Phase 3	TERMINATED	Adjuvant Aspirin Treatment for Colon Cancer Patients
NCT02519140	Phase 3	WITHDRAWN	Assessing How the Viscosity of Submucosal Gel Injections Helps With Endoscopic Mucosal Resections
NCT02572141	Phase 3	ACTIVE_NOT_RECRUITING	FOLFOX or CAPOX Perioperative Chemotherapy Versus Postoperative Chemotherapy for Locally Advanced Colon Cancer (OPTICAL)
NCT02588248	Phase 3	TERMINATED	L-Menthol Injection as a Novel Technique During Colonoscopy
NCT02682589	Phase 3	UNKNOWN	Open Versus Laparoscopic Complete Mesocolic Excision for Locally Advanced Colon Cancer
NCT02912052	Phase 3	UNKNOWN	Perioperative Chemotherapy VS Postoperative Chemotherapy for the Treatment of Colon Cancer With Resectable Liver Metastasis
NCT02912559	Phase 3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT02928692	Phase 3	UNKNOWN	Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium
NCT02967289	Phase 3	COMPLETED	IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for POLD1 across ~30M SureChEMBL compounds — explore on Sugi Predict.