POLE

Summary

POLE (DNA polymerase epsilon, catalytic subunit, HGNC:9177) is a protein-coding gene on chromosome 12q24.33, encoding DNA polymerase epsilon catalytic subunit A (Q07864). Catalytic component of the DNA polymerase epsilon complex. In precision oncology, POLE Mutation confers sensitivity to Pembrolizumab in Glioblastoma (CIViC Level C); 3 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature.

Source: NCBI Gene 5426 — RefSeq curated summary.

At a glance

• Gene–disease (curated): POLE-related polyposis and colorectal cancer syndrome (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 11,128 total — 354 pathogenic, 128 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 36 tissues, sQTL in 33 (q < 0.05)
• Phenotypes (HPO): 116
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.75 (unconstrained)
• MANE Select transcript: NM_006231
• Interaction hub: 2,173 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9177
Approved symbol	POLE
Name	DNA polymerase epsilon, catalytic subunit
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	POLE1
Ensembl gene	ENSG00000177084
Ensembl biotype	protein_coding
OMIM	174762
Entrez	5426

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 10 retained_intron, 10 nonsense_mediated_decay, 4 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000320574

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 5, TSL 4: 3, TSL 5: 3

ENST00000320574, ENST00000416953, ENST00000434528, ENST00000441786, ENST00000503265, ENST00000534922, ENST00000535270, ENST00000537064, ENST00000538196, ENST00000539215, ENST00000539357, ENST00000539618, ENST00000540987, ENST00000541627, ENST00000544414, ENST00000544870, ENST00000545015, ENST00000672002, ENST00000672742, ENST00000699981, ENST00000699982, ENST00000699983, ENST00000699984, ENST00000699985, ENST00000937600, ENST00001141704

RefSeq mRNA: 1 — MANE Select: NM_006231 NM_006231

CCDS: CCDS9278

Canonical transcript exons

ENST00000320574 — 49 exons

Exon	Start	End
ENSE00001221880	132676094	132676204
ENSE00001221886	132676546	132676653
ENSE00001221895	132677363	132677443
ENSE00001221904	132677578	132677719
ENSE00001221910	132679497	132679651
ENSE00001221917	132679954	132680046
ENSE00001221926	132680178	132680222
ENSE00001221932	132680607	132680687
ENSE00002699740	132687254	132687342
ENSE00003469256	132642820	132642996
ENSE00003471189	132681138	132681279
ENSE00003474748	132643407	132643560
ENSE00003481557	132623762	132624810
ENSE00003484451	132632315	132632508
ENSE00003493093	132642506	132642729
ENSE00003498236	132675735	132675820
ENSE00003501253	132667503	132667648
ENSE00003505045	132638014	132638139
ENSE00003505152	132643837	132643977
ENSE00003530501	132657136	132657258
ENSE00003531158	132643224	132643330
ENSE00003538362	132668635	132668737
ENSE00003540408	132664370	132664462
ENSE00003548640	132641647	132641851
ENSE00003555146	132624905	132624994
ENSE00003574090	132673164	132673277
ENSE00003581276	132672627	132672839
ENSE00003582134	132665302	132665450
ENSE00003596682	132639125	132639298
ENSE00003598809	132660969	132661164
ENSE00003607611	132673575	132673707
ENSE00003608285	132657349	132657429
ENSE00003612691	132642177	132642397
ENSE00003621968	132675398	132675517
ENSE00003627930	132625645	132625770
ENSE00003637825	132664004	132664148
ENSE00003639152	132661527	132661684
ENSE00003639545	132649306	132649515
ENSE00003646829	132668356	132668502
ENSE00003652503	132668811	132668939
ENSE00003654243	132659295	132659509
ENSE00003655346	132632664	132632795
ENSE00003666262	132626117	132626317
ENSE00003673423	132634186	132634378
ENSE00003674568	132635892	132636024
ENSE00003684194	132648929	132649072
ENSE00003691443	132672215	132672322
ENSE00003726606	132657868	132657970
ENSE00003730711	132649677	132649889

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 94.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.9565 / max 472.2981, expressed in 1770 samples.

Highest expression (Bgee): hemisphere of cerebellum, testis, cerebellar hemisphere, cerebellar cortex, sural nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

POLE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 36 tissues and its splicing (sQTL) in 33 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 69 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	1.2e-97	-1.19	12:132622323:T:C
Brain Cerebellar Hemisphere	eqtl	5.2e-95	-1.08	12:132622323:T:C
Muscle Skeletal	sqtl	2.0e-60	+0.91	12:132658746:T:G
Muscle Skeletal	eqtl	3.9e-53	-0.39	12:132659203:A:G
Brain Cerebellum	sqtl	7.4e-53	+1.47	12:132622323:T:C
Skin Sun Exposed Lower leg	sqtl	8.5e-50	-0.96	12:132676210:C:G
Testis	sqtl	1.1e-49	+1.33	12:132636864:C:T
Brain Frontal Cortex BA9	eqtl	1.3e-48	+0.83	12:132682939:C:T
Brain Nucleus accumbens basal ganglia	eqtl	4.7e-48	-0.79	12:132629721:A:C
Skin Not Sun Exposed Suprapubic	sqtl	3.9e-46	-1.03	12:132660160:C:T
Adipose Subcutaneous	sqtl	2.4e-44	-0.88	12:132629709:A:G
Brain Cortex	eqtl	1.2e-41	-0.83	12:132667231:C:T
Brain Cerebellar Hemisphere	sqtl	1.1e-35	-1.48	12:132653619:C:T
Cells EBV-transformed lymphocytes	sqtl	3.8e-32	-1.08	12:132636864:C:T
Nerve Tibial	eqtl	7.1e-31	-0.28	12:132686336:C:G
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-29	+0.26	12:132636864:C:T
Brain Caudate basal ganglia	eqtl	1.1e-27	-0.62	12:132667231:C:T
Nerve Tibial	sqtl	3.7e-27	+0.78	12:132676210:C:G
Artery Tibial	sqtl	2.8e-25	+0.77	12:132676210:C:G
Cells Cultured fibroblasts	sqtl	7.8e-25	+0.87	12:132685415:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
134223	23.4121	1763
134221	0.2800	122
134224	0.2644	103

Top tissues by expression

showing 100 of 267 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.93	gold quality
right testis	UBERON:0004534	94.74	gold quality
cerebellar hemisphere	UBERON:0002245	94.70	gold quality
left testis	UBERON:0004533	94.63	gold quality
cerebellar cortex	UBERON:0002129	94.46	gold quality
sural nerve	UBERON:0015488	93.00	gold quality
cerebellum	UBERON:0002037	92.23	gold quality
ventricular zone	UBERON:0003053	91.78	gold quality
spleen	UBERON:0002106	91.10	gold quality
testis	UBERON:0000473	91.02	gold quality
endometrium epithelium	UBERON:0004811	90.13	gold quality
skin of abdomen	UBERON:0001416	89.89	gold quality
skin of leg	UBERON:0001511	89.80	gold quality
ganglionic eminence	UBERON:0004023	89.56	gold quality
right lobe of liver	UBERON:0001114	89.49	gold quality
granulocyte	CL:0000094	88.98	gold quality
mucosa of transverse colon	UBERON:0004991	88.29	gold quality
lower esophagus mucosa	UBERON:0035834	87.92	gold quality
mucosa of stomach	UBERON:0001199	87.83	gold quality
body of stomach	UBERON:0001161	87.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.18	gold quality
cortical plate	UBERON:0005343	87.07	gold quality
transverse colon	UBERON:0001157	87.02	gold quality
zone of skin	UBERON:0000014	86.82	gold quality
bone marrow cell	CL:0002092	86.61	gold quality
stomach	UBERON:0000945	86.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.17	gold quality
left ovary	UBERON:0002119	86.09	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.83	gold quality
lower esophagus	UBERON:0013473	85.81	gold quality
right ovary	UBERON:0002118	85.49	gold quality
esophagus	UBERON:0001043	85.35	gold quality
small intestine	UBERON:0002108	85.31	gold quality
esophagus mucosa	UBERON:0002469	85.20	gold quality
popliteal artery	UBERON:0002250	85.16	gold quality
tibial artery	UBERON:0007610	85.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.09	gold quality
gastrocnemius	UBERON:0001388	85.08	gold quality
left uterine tube	UBERON:0001303	85.04	gold quality
muscle of leg	UBERON:0001383	85.00	gold quality
ectocervix	UBERON:0012249	85.00	gold quality
colonic epithelium	UBERON:0000397	84.96	gold quality
apex of heart	UBERON:0002098	84.79	gold quality
calcaneal tendon	UBERON:0003701	84.78	gold quality
aorta	UBERON:0000947	84.77	gold quality
paraflocculus	UBERON:0005351	84.75	silver quality
tibial nerve	UBERON:0001323	84.70	gold quality
body of pancreas	UBERON:0001150	84.66	gold quality
body of uterus	UBERON:0009853	84.54	gold quality
thoracic aorta	UBERON:0001515	84.51	gold quality
ascending aorta	UBERON:0001496	84.49	gold quality
minor salivary gland	UBERON:0001830	84.40	gold quality
embryo	UBERON:0000922	84.15	gold quality
descending thoracic aorta	UBERON:0002345	83.95	gold quality
rectum	UBERON:0001052	83.44	gold quality
upper lobe of left lung	UBERON:0008952	83.42	gold quality
colon	UBERON:0001155	83.23	gold quality
intestine	UBERON:0000160	83.22	gold quality
metanephros cortex	UBERON:0010533	83.06	gold quality
bone marrow	UBERON:0002371	82.98	gold quality
endocervix	UBERON:0000458	82.96	gold quality
left coronary artery	UBERON:0001626	82.68	gold quality
fundus of stomach	UBERON:0001160	82.61	gold quality
large intestine	UBERON:0000059	82.52	gold quality
upper lobe of lung	UBERON:0008948	82.52	gold quality
omental fat pad	UBERON:0010414	82.50	gold quality
peritoneum	UBERON:0002358	82.45	gold quality
right lung	UBERON:0002167	82.42	gold quality
lymph node	UBERON:0000029	82.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.34	gold quality
sigmoid colon	UBERON:0001159	82.30	gold quality
right uterine tube	UBERON:0001302	82.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.24	gold quality
mouth mucosa	UBERON:0003729	82.10	gold quality
stromal cell of endometrium	CL:0002255	82.01	gold quality
right atrium auricular region	UBERON:0006631	81.98	gold quality
vagina	UBERON:0000996	81.91	gold quality
saliva-secreting gland	UBERON:0001044	81.85	gold quality
liver	UBERON:0002107	81.85	gold quality
ovary	UBERON:0000992	81.78	gold quality
right frontal lobe	UBERON:0002810	81.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.78	gold quality
coronary artery	UBERON:0001621	81.64	gold quality
right lobe of thyroid gland	UBERON:0001119	81.43	gold quality
monocyte	CL:0000576	81.38	gold quality
left lobe of thyroid gland	UBERON:0001120	81.30	gold quality
leukocyte	CL:0000738	81.24	gold quality
tendon	UBERON:0000043	81.17	gold quality
frontal pole	UBERON:0002795	81.08	gold quality
mononuclear cell	CL:0000842	81.03	gold quality
cardiac atrium	UBERON:0002081	80.57	gold quality
tonsil	UBERON:0002372	80.42	gold quality
muscle organ	UBERON:0001630	80.40	gold quality
thyroid gland	UBERON:0002046	80.22	gold quality
anatomical system	UBERON:0000467	80.12	gold quality
prostate gland	UBERON:0002367	80.11	gold quality
pancreas	UBERON:0001264	80.07	gold quality
thymus	UBERON:0002370	80.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.26

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Bone marrow	tissue	20.8
Thymus	tissue	14.1
Skin 1	tissue	10.7
Testis	tissue	9.3
Spleen	tissue	8.4
Small intestine	tissue	6.3
Tonsil	tissue	6.3
Lymph node	tissue	6.2
Duodenum	tissue	5.9
Rectum	tissue	5.6
Appendix	tissue	5.5
Stomach 1	tissue	4.6
Liver	tissue	4.5
Salivary gland	tissue	4.4
Colon	tissue	4.4
Placenta	tissue	4.4
Skeletal muscle	tissue	4.0
Choroid plexus	tissue	3.8
Ovary	tissue	3.7
Vagina	tissue	3.7
Pancreas	tissue	3.6
Hippocampus	tissue	3.5
Esophagus	tissue	3.4
Endometrium 1	tissue	3.4
Smooth muscle	tissue	3.3
Prostate	tissue	3.3
Breast	tissue	3.0
Seminal vesicle	tissue	3.0
Postcentral gyrus	tissue	3.0
Gallbladder	tissue	2.9
Lung	tissue	2.8
Fallopian tube	tissue	2.8
Adipose tissue	tissue	2.6
Tongue	tissue	2.6
Heart muscle	tissue	2.5
Parathyroid gland	tissue	2.3
Cervix	tissue	2.2
Nucleus accumbens	tissue	2.2
Urinary bladder	tissue	2.1
Locus coeruleus	tissue	2.1
Epididymis	tissue	2.0
Retina	tissue	1.9
Thyroid gland	tissue	1.7
Pituitary gland	tissue	1.5
Adrenal gland	tissue	1.4
Kidney	tissue	1.3
Basal ganglia	tissue	0.8
Cerebellum	tissue	0.8
Amygdala	tissue	0.7
Hippocampal formation	tissue	0.7
Olfactory bulb	tissue	0.7
Cerebral cortex	tissue	0.6
Putamen	tissue	0.6
Spinal cord	tissue	0.6
Corpus callosum	tissue	0.6
Entorhinal cortex	tissue	0.6
Ventral forebrain	tissue	0.6
Retrosplenial and cingulate cortex	tissue	0.6
Retrosplenial cortex	tissue	0.6
Temporal cortex	tissue	0.6

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Vermis (9.4), Flocculonodular lobe (8.6), Cerebellar cortex (8.1), Hippocampus, CA3 (5.5), Dentate gyrus (4.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting POLE by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 45 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-485-5P	99.10	64.78	1889

Functional genomics

gnomAD constraint: pLI 2.74e-38, LOEUF 0.75, missense Z 2.67 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000320574 splits into 5 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
12:132,624,700–132,661,015	1551 / 1686.1	0.92	no
12:132,661,016–132,661,139	19 / 51.5	0.37	no
12:132,661,140–132,664,101	101 / 115.4	0.87	no
12:132,664,102–132,664,438	21 / 51.9	0.40	no
12:132,664,439–132,687,315	1011 / 1111.7	0.91	no
ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): LOU-NH91 (-2.903), KP-N-YN (-2.867), RERF-GC-1B (-2.713), EFO-21 (-2.572), DB (-2.561), BT-12 (-2.53), L-363 (-2.512), HEL (-2.479), Hs 294T (-2.397), HCC1937 (-2.396), G-292, clone A141B1 (-2.343), NCI-H747 (-2.341), CCF-STTG1 (-2.313), COV362 (-2.311), KMRC-20 (-2.298).

Literature-anchored findings (GeneRIF, showing 40)

• It is hypothesized from these observations that pol epsilon and PCNA have separate but associated functions early in S phase and that pol epsilon participates with PCNA in DNA replication late in S phase. (PMID:11741962)
• SNPs associated with prognosis of lung cancer was mapped to POLE. (PMID:17855454)
• An AATT deletion in the 55 kDa small subunit DNA sequence of DNA polymerase epsilon is associated with breast cancer (PMID:19129559)
• Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE, and FAM3D, were associated with narcolepsy. (PMID:20677014)
• Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8. (PMID:20826785)
• Mutation in the POLE gene that encodes p261 catalytic subunit of pol epsilon is the first found in human cells. (PMID:21157497)
• In vitro gap-directed translesion DNA synthesis of an abasic site involving human DNA polymerases epsilon, lambda, and beta. (PMID:21757740)
• 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)
• Data show that using a 200-nt primed circular DNA substrate, the combined action of DNA polymerase epsilon and the Cdc45/Mcm2-7/GINS (CMG complex) leads to the formation of products >10 kb in length. (PMID:22474384)
• Pol epsilon and Pol alpha/delta seem to pursue their functions at least in part independently in late S phase (PMID:22887995)
• Pol epsilon is a likely source of ribonucleotides in human genomic DNA. (PMID:23093410)
• observed impairment in proliferation and G1- to S-phase progression in patients’ T lymphocytes. Polepsilon1 depletion also impaired G1- to S-phase progression in B lymphocytes, chondrocytes, and osteoblasts. (PMID:23230001)
• 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)
• To catalyze leading-strand synthesis in vivo, Polepsilon likely interacts with its three smaller subunits and additional replication factors in order to assemble a replication complex and significantly enhance its polymerization processivity. (PMID:24020356)
• Mutant Pol epsilon causes replication errors in vivo. In colorectal patients, the single allele mutations are microsatellite stable with a large increase in base pair substitutions, consistent with requirement of additional factors for tumor development. (PMID:24051051)
• The POLE1 p.S297F mutation was frequent in Chinese ovarian endometrioid carcinoma. (PMID:24472300)
• 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)
• Heterozygosity for the variant allele caused a strong mutator effect comparable with that of complete mismatch repair deficiency, providing an explanation for why loss of heterozygosity is not required for the development of Polepsilon-mutant human tumors. (PMID:24525744)
• A new amino-acid substitution in POLE was identified resulting in a predisposition to a broad spectrum of tumours in addition to colorectal cancers. (PMID:24788313)
• POLE exonuclease domain mutations occur in a subset of grade 3 endometrioid carcinomas and are associated with good clinical outcome. (PMID:24844595)
• POLE mutations have been found in other tumor types, though at lower frequency, suggesting roles in tumorigenesis more broadly in different tissue types. [Review] (PMID:24861832)
• Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25, FGFR1, and POLE. (PMID:25184702)
• Somatic POLE exonuclease domain mutations are common in endometrioid endometrial cancer, are observed with equal frequency in tumors with microsatellite stability and those with microsatellite instability, and are not associated with survival. (PMID:25224212)
• Data indicate that exonuclease domain of DNA polymerase epsilon (POLE-exo*) mutants generate a unique pattern of replication errors. (PMID:25228659)
• 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)
• the recognition of ultramutated endometrial carcinomas with POLE exonuclease domain mutation is important given their favorable outcome (PMID:25394778)
• The 3’–>5’ exonuclease activity of hPol further enhances polymerization fidelity by an unprecedented 3.5 x 10(2) to 1.2 x 10(4)-fold. (PMID:25414327)
• Data indicate that the polymerase (DNA directed), epsilon protein (POLE) mutation c.1270C>G;p.Leu424Val was detected in 1.5% (4/266) of all patients, 4% (3/77) of all familial cases and 7% (2/30) of familial polyposis cases. (PMID:25529843)
• The kinetic parameters of the truncated catalytic subunit and holoenzyme of human DNA polymerase varepsilon are compared. (PMID:25684708)
• Identified a genomically, histologically, and clinically distinct subgroup of high-grade gliomas that harbored somatic POLE mutations and carried an improved prognosis. (PMID:25740784)
• A novel c.1373A>T (p.Tyr458Phe)POLE mutation associated with cancers of colon, pancreas, ovaries and small intestine. (PMID:25860647)
• POLE proofreading-mutant endometrial cancers are characterized by a robust intratumoral T-cell response, which correlates with, and may be caused by an enrichment of antigenic neopeptides (PMID:25878334)
• POLE ultra-mutated-tumors are significantly more immunogenic when compared to POLE (-) tumors, in particular to the helper arm of the immune system. (PMID:25931171)
• 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)
• Missense point mutations in POLE gene is associated with Ovarian Endometrioid Carcinoma. (PMID:26166557)
• Results show that that mutated POLE 1 are associated with high neoantigen loads and may be excellent candidates for PD-1-targeted immunotherapies. (PMID:26181000)
• POLE mutations are associated with cutaneous melanoma. (PMID:26251183)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pole	ENSDARG00000058533
mus_musculus	Pole	ENSMUSG00000007080
rattus_norvegicus	Pole	ENSRNOG00000037449
drosophila_melanogaster	PolE1	FBGN0264326
caenorhabditis_elegans	pole-1	WBGENE00009368

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1196391) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged spleen	1
increased tumor incidence	1
premature death	1
increased intestinal adenoma incidence	1
increased intestinal adenocarcinoma incidence	1
increased lung tumor incidence	1
increased small intestine adenocarcinoma incidence	1
increased colon adenocarcinoma incidence	1
increased histiocytic sarcoma incidence	1
increased adenoma incidence	1
embryonic lethality between implantation and placentation, complete penetrance	1
increased lymphoma incidence	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
Cryptococcus deneoformans JEC21	P0CN26	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CN27	100.0%	Diamond
Aspergillus nidulans FGSC A4	O93845	85.5%	Diamond
Aspergillus fumigatus Af293	Q4WXH8	85.5%	Diamond
Arabidopsis thaliana	F4HW04	85.2%	Diamond
Saccharomyces cerevisiae S288C	P21951	68.5%	Diamond
Nakaseomyces glabratus CBS 138	Q6FNY7	68.4%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CUS7	66.2%	Diamond
Eremothecium gossypii ATCC 10895	Q752B8	66.0%	Diamond
Debaryomyces hansenii CBS767	Q6BNG2	58.4%	Diamond
Mycosarcoma maydis	Q4PFV5	55.8%	Diamond
Schizosaccharomyces pombe 972h-	P87154	48.2%	Diamond
Yarrowia lipolytica CLIB122	Q6C4J0	42.6%	Diamond
Dictyostelium discoideum	Q54RD4	42.2%	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
P2RX2	protein-coding	22953
PGAM5	protein-coding	192111
PXMP2	protein-coding	5827
LRCOL1	protein-coding	100507055
ANKLE2	protein-coding	23141

Protein

Protein identifiers

DNA polymerase epsilon catalytic subunit A — Q07864 (reviewed: Q07864)

Alternative names: 3’-5’ exodeoxyribonuclease, DNA polymerase II subunit A

All UniProt accessions (9): A0A087WW42, A0A087WX51, A0A5F9ZHD6, A0A5F9ZI42, A0A8V8TQH1, A0A8V8TQW1, F5H1D6, F5H7E4, Q07864

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork. Has 3’-5’ proofreading exonuclease activity that corrects errors arising during DNA replication. Involved in DNA synthesis during DNA repair. Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation.

Subunit / interactions. Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1.

Subcellular location. Nucleus.

Disease relevance. Colorectal cancer 12 (CRCS12) [MIM:615083] 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. CRCS12 is characterized by a high-penetrance predisposition to the development of colorectal adenomas and carcinomas, with a variable tendency to develop multiple and large tumors. Onset is usually before age 40 years. The histologic features of the tumors are unremarkable. Disease susceptibility is associated with variants affecting the gene represented in this entry. Facial dysmorphism, immunodeficiency, livedo, and short stature (FILS) [MIM:615139] A syndrome characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, and immunodeficiency resulting in recurrent infections. Growth impairment is observed during early childhood and results in variable short stature in adulthood. The disease is caused by variants affecting the gene represented in this entry. Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency (IMAGEI) [MIM:618336] An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth failure, metaphyseal dysplasia, adrenal hypoplasia congenita, growth hormone deficiency, genital anomalies, and immunodeficiency resulting in increased infections. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DNA polymerase activity domain resides in the N-terminal half of the protein, while the C-terminus is necessary for maintenance of the complex. The CysA-type zinc finger is required for PCNA-binding. The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.

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

RefSeq proteins (1): NP_006222* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006133	DNA-dir_DNA_pol_B_exonuc	Domain
IPR006172	DNA-dir_DNA_pol_B	Family
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR013697	DNA_pol_e_suA_C	Domain
IPR023211	DNA_pol_palm_dom_sf	Homologous_superfamily
IPR029703	POL2	Family
IPR036397	RNaseH_sf	Homologous_superfamily
IPR042087	DNA_pol_B_thumb	Homologous_superfamily
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR054475	Znf-DPOE	Domain
IPR055191	POL2_thumb	Domain

Pfam: PF03104, PF08490, PF22634, PF22912, PF23250

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 (249 total): strand 86, helix 81, sequence variant 42, turn 20, binding site 8, modified residue 4, region of interest 2, compositionally biased region 2, chain 1, zinc finger region 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures by resolution:

PDB	Title	Method	Resolution (Å)
5VBN	Crystal Structure of human DNA polymerase epsilon B-subunit in complex with C-terminal …	X-RAY DIFFRACTION	2.35
7PLO	H. sapiens replisome-CUL2/LRR1 complex	ELECTRON MICROSCOPY	2.8
9B8T	Human polymerase epsilon bound to PCNA and DNA in the nucleotide bound state	ELECTRON MICROSCOPY	2.95
9NE6	Human polymerase epsilon bound to PCNA and DNA with an in-situ-generated mismatch in the …	ELECTRON MICROSCOPY	3.11
7PFO	Core human replisome	ELECTRON MICROSCOPY	3.2
9F6I	Human DNA Polymerase epsilon bound to T-C mismatched DNA (Post-Insertion state)	ELECTRON MICROSCOPY	3.3
9SRI	Human DNA polymerase epsilon bound to DNA blunt end	ELECTRON MICROSCOPY	3.3
9NE7	Human polymerase epsilon bound to PCNA and DNA with an in-situ-generated mismatch in the …	ELECTRON MICROSCOPY	3.53
9F6D	Human DNA polymerase epsilon bound to DNA and PCNA (open conformation)	ELECTRON MICROSCOPY	3.6
9NE8	Human polymerase epsilon bound to PCNA and DNA with an in-situ-generated mismatch in the …	ELECTRON MICROSCOPY	3.6
9F6E	Human DNA polymerase epsilon bound to DNA and PCNA (ajar conformation)	ELECTRON MICROSCOPY	3.74
9F6F	Human DNA polymerase epsilon bound to DNA and PCNA (closed conformation)	ELECTRON MICROSCOPY	3.75
9NEA	Human polymerase epsilon bound to PCNA and DNA with a pre-existing mismatch in the …	ELECTRON MICROSCOPY	3.81
9NE9	Human polymerase epsilon bound to PCNA and DNA with a pre-existing mismatch in the …	ELECTRON MICROSCOPY	3.88
9F6J	Human DNA Polymerase epsilon bound to T-C mismatched DNA (Polymerase Arrest state)	ELECTRON MICROSCOPY	3.9
9F6L	Human DNA Polymerase epsilon bound to T-C mismatched DNA (Mismatch Excision state)	ELECTRON MICROSCOPY	3.9
9F6K	Human DNA Polymerase epsilon bound to T-C mismatched DNA (Frayed Substrate state)	ELECTRON MICROSCOPY	4.2
9B8S	Human polymerase epsilon bound to PCNA and DNA in the nucleotide exchange state	ELECTRON MICROSCOPY	5.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07864-F1	80.32	0.31

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutated cancer genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; plasma membrane

Antibody reliability (HPA): IF enhanced

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
2190	Zn(2+)
2221	[4Fe-4S] cluster
2224	[4Fe-4S] cluster
2236	[4Fe-4S] cluster
2238	[4Fe-4S] cluster
2158	Zn(2+)
2161	Zn(2+)
2187	Zn(2+)

Post-translational modifications (4)

Type	Positions
Phosphoserine	1184, 1297, 1317, 1940

Function

Pathways and Gene Ontology

Reactome pathways

10 curated (TAS) of 30; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

30 pathways:

ID	Pathway	Evidence
R-HSA-68962	Activation of the pre-replicative complex	curated
R-HSA-68952	DNA replication initiation	curated
R-HSA-5696400	Dual Incision in GG-NER	curated
R-HSA-6782135	Dual incision in TC-NER	curated
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER	curated
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER	curated
R-HSA-5685942	HDR through Homologous Recombination (HRR)	curated
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair	curated
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex	curated
R-HSA-5656169	Termination of translesion DNA synthesis	curated
R-HSA-73884	Base Excision Repair	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
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-69002	DNA Replication Pre-Initiation	—
R-HSA-69206	G1/S Transition	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-453279	Mitotic G1 phase and G1/S transition	—
R-HSA-5696398	Nucleotide Excision Repair	—
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-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: 511 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_DNA_REPLICATION, BENPORATH_ES_WITH_H3K27ME3, FISCHER_G1_S_CELL_CYCLE, GOMF_NUCLEASE_ACTIVITY, GOBP_DNA_STRAND_ELONGATION_INVOLVED_IN_DNA_REPLICATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, KAUFFMANN_DNA_REPAIR_GENES, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOTIDE_EXCISION_REPAIR, GOMF_DNA_POLYMERASE_ACTIVITY

GO Biological Process (13): G1/S transition of mitotic cell cycle (GO:0000082), mitotic cell cycle (GO:0000278), DNA synthesis involved in DNA repair (GO:0000731), DNA replication (GO:0006260), DNA-templated DNA replication (GO:0006261), leading strand elongation (GO:0006272), base-excision repair, gap-filling (GO:0006287), nucleotide-excision repair, DNA gap filling (GO:0006297), DNA replication proofreading (GO:0045004), embryonic organ development (GO:0048568), DNA repair (GO:0006281), DNA damage response (GO:0006974), DNA biosynthetic process (GO:0071897)

GO Molecular Function (15): nucleotide binding (GO:0000166), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-directed DNA polymerase activity (GO:0003887), zinc ion binding (GO:0008270), single-stranded DNA 3’-5’ DNA exonuclease activity (GO:0008310), 4 iron, 4 sulfur cluster binding (GO:0051539), nucleic acid binding (GO:0003676), protein binding (GO:0005515), 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), epsilon DNA polymerase complex (GO:0008622)

Reactome top-level categories

15 top-level categories:

Category	Pathways
DNA Damage Bypass	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	2
DNA Repair	2
Nucleotide Excision Repair	2
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
Synthesis of DNA	1
DNA Replication Pre-Initiation	1
G1/S Transition	1
Resolution of Abasic Sites (AP sites)	1
Cell Cycle, Mitotic	1
DNA Double-Strand Break Repair	1
Homology Directed Repair	1

GO top-level categories

43 GO namespaces:

Category	Terms
DNA metabolic process	5
DNA biosynthetic process	3
binding	3
DNA repair	2
catalytic activity	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cell cycle	1
mitotic nuclear division	1
DNA replication	1
DNA replication, synthesis of primer	1
DNA strand elongation involved in DNA replication	1
DNA replication, removal of RNA primer	1
base-excision repair	1
nucleotide-excision repair	1
DNA-templated DNA replication maintenance of fidelity	1
embryo development	1
animal organ development	1
DNA damage response	1
cellular response to stress	1
nucleic acid biosynthetic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
DNA polymerase activity	1
transition metal ion binding	1
3’-5’-DNA exonuclease activity	1
single-stranded DNA exodeoxyribonuclease activity	1
iron-sulfur cluster binding	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
cellular anatomical structure	1
membrane	1
cell periphery	1
nuclear chromosome	1
DNA polymerase complex	1
nuclear protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
DNA replication	BP	mutant phenotype
DNA synthesis involved in DNA repair	BP	mutant phenotype
DNA-templated DNA replication	BP	direct assay
G1/S transition of mitotic cell cycle	BP	mutant phenotype
base-excision repair, gap-filling	BP	direct assay
nucleotide-excision repair, DNA gap filling	BP	mutant phenotype
epsilon DNA polymerase complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
DNA binding	MF	direct assay
DNA-directed DNA polymerase activity	MF	mutant phenotype
chromatin binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,173 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLE	POLD1	P28340	979
POLE	POLE2	P56282	960
POLE	POLE4	Q9NR33	930
POLE	POLE3	Q9NRF9	913
POLE	MSH6	P52701	866
POLE	REV3L	O60673	852
POLE	MSH2	P43246	842
POLE	MLH1	P40692	834
POLE	PMS2	P54278	828
POLE	MSH3	P20585	801
POLE	MUTYH	Q9UIF7	784
POLE	LIG3	P49916	772
POLE	XRCC1	P18887	748
POLE	NTHL1	P78549	730
POLE	LIG1	P18858	730

IntAct

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

21 partners by confidence:

Partner	Interaction type	MIscore	Records
POLE2	physical association	0.860	10
BRAF	physical association	0.600	4
ABHD16A	physical association	0.560	3
POLE4	association	0.530	2
LRRK2	direct interaction	0.440	1
BLTP3A	physical association	0.400	1
CFTR	physical association	0.370	1
HSPA8	association	0.350	1
LIAS	association	0.350	1
FBXW7	proximity	0.270	4
SMAD4	proximity	0.270	4
SMARCA4	proximity	0.270	4
SPOP	proximity	0.270	4
AKT1	proximity	0.270	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
TP53	proximity	0.270	1
DISC1	physical association	0.000	1
MYC	physical association	0.000	1
WHR1	physical association	0.000	1

BioGRID (207 interactions; top human partners by supporting records): POLE2 (Affinity Capture-MS; 11 records), PCNA (Co-fractionation; 6 records), POLE3 (Co-fractionation; 6 records), CIAO1 (Affinity Capture-Western; 4 records), MMS19 (Affinity Capture-Western; 4 records), CLSPN (Affinity Capture-Western; 3 records), DNAJC7 (Affinity Capture-MS; 3 records), LRRC46 (Affinity Capture-MS; 3 records), MYC (Affinity Capture-MS; 3 records), POLE4 (Co-fractionation; 3 records), BAG2 (Affinity Capture-MS; 2 records), C16orf45 (Affinity Capture-MS; 2 records), DKKL1 (Affinity Capture-MS; 2 records), FAM96A (Affinity Capture-MS; 2 records), KRAS (Synthetic Lethality; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
POLE	“form complex”	“DNA polymerase epsilon”	binding

Protein complexes (CORUM) (5)

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

5 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 polymerase epsilon	4	POLE, POLE2, POLE3, POLE4

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
Ub-specific processing proteases	5	15.6×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	72.6×	4e-06
positive regulation of gene expression	5	9.7×	5e-03
negative regulation of apoptotic process	5	8.7×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — ACC, BLCA.

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 POLE: 11,128 ClinVar records (482 pathogenic / likely pathogenic); 4 CIViC cancer variants; 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

11,128 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	354
Likely pathogenic	128
Uncertain significance	5512
Likely benign	3744
Benign	131

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 482 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
40046	NM_006231.4(POLE):c.1270C>G (p.Leu424Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
2717088	NM_006231.4(POLE):c.5678+1G>T	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4772281	NM_006231.4(POLE):c.507_508dup (p.Ile170fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
806968	NM_006231.4(POLE):c.5379-5_5384del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
928703	NM_006231.4(POLE):c.1306C>T (p.Pro436Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2636782	NM_006231.4(POLE):c.3276-1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2582706	NM_006231.4(POLE):c.2154del (p.Lys717_Tyr718insTer)	Pathogenic	criteria provided, single submitter	2
405692	NM_006231.4(POLE):c.3501_3502insGGTCAAA (p.His1168fs)	Pathogenic	criteria provided, single submitter	1
405812	NM_006231.4(POLE):c.3510dup (p.Leu1171fs)	Pathogenic	criteria provided, single submitter	1
405813	NM_006231.4(POLE):c.1673del (p.Cys558fs)	Pathogenic	criteria provided, single submitter	1
473697	NM_006231.4(POLE):c.4900del (p.Arg1634fs)	Pathogenic	criteria provided, single submitter	1
540728	NM_006231.4(POLE):c.340C>T (p.Arg114Ter)	Pathogenic	criteria provided, single submitter	1
540730	NM_006231.4(POLE):c.4420del (p.Ala1474fs)	Pathogenic	criteria provided, single submitter	1
540766	NM_006231.4(POLE):c.3534C>A (p.Tyr1178Ter)	Pathogenic	criteria provided, single submitter	1
540827	NM_006231.4(POLE):c.6434_6438del (p.Arg2145fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore POLE’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; 23 predictions of 4,615):

Position(s)	Effect	Δscore	Sites
12:132624811	acceptor_loss	1.0000
12:132624815	acceptor_gain	1.0000
12:132624903–132624904	donor_loss	1.0000	5
12:132625643–132625644	donor_loss	1.0000	3
12:132634184–132634185	donor_loss	1.0000	4
12:132635971–132635972	acceptor_gain	1.0000	2
12:132638012–132638013	donor_loss	1.0000	4
12:132641630	donor_gain	1.0000
12:132641677	donor_gain	1.0000
12:132641682	donor_gain	1.0000

AlphaMissense

5,865 missense substitutions predicted likely pathogenic (of 15,124 scored), across 1,433 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
M630	9	0.979	0.999
M820	9	0.969	0.998
M940	9	0.969	1.000
M831	9	0.961	0.998
M295	9	0.959	0.998
M1039	9	0.952	0.999
M299	9	0.938	0.993
M444	9	0.891	0.991
M506	9	0.891	0.988
H624	8	1.000	1.000
D626	8	1.000	1.000
D862	8	1.000	1.000
D860	8	0.999	1.000
D414	8	0.998	1.000
D462	8	0.998	1.000
D934	8	0.998	0.999
D275	8	0.997	0.999
D406	8	0.997	0.999
F971	8	0.997	1.000
N813	8	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Skin Cutaneous Melanoma (TCGA)	unfavorable	0.000682

Disease associations

OMIM: gene MIM:174762 | disease phenotypes: MIM:615083, MIM:618336, MIM:615139, MIM:219721, MIM:114500

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
POLE-related polyposis and colorectal cancer syndrome	Definitive	Autosomal dominant	2
colorectal cancer, susceptibility to, 12	Strong	Autosomal dominant	3
facial dysmorphism-immunodeficiency-livedo-short stature syndrome	Strong	Autosomal recessive	4
intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency	Strong	Autosomal dominant	2
Polymerase proofreading-related adenomatous polyposis	Supportive	Autosomal dominant
IMAGe syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
POLE-related polyposis and colorectal cancer syndrome	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 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
Congenital adrenal hypoplasia	green
DDG2P	green
Fetal anomalies	green
GI tract tumours	green
Inherited polyposis and early onset colorectal cancer - germline testing	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (14): colorectal cancer, susceptibility to, 12 (MONDO:0014038), intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency (MONDO:0032684), facial dysmorphism-immunodeficiency-livedo-short stature syndrome (MONDO:0014058), hereditary neoplastic syndrome (MONDO:0015356), myoepithelial tumor (MONDO:0002380), cystic fibrosis-gastritis-megaloblastic anemia syndrome (MONDO:0009062), familial colorectal cancer type X (MONDO:0018604), Polymerase proofreading-related adenomatous polyposis (MONDO:0018653), familial colorectal cancer (MONDO:0023113), POLE-related polyposis and colorectal cancer syndrome (MONDO:0100287), colorectal carcinoma (MONDO:0024331), colon carcinoma (MONDO:0002032), colorectal cancer (MONDO:0005575), IMAGe syndrome (MONDO:0013873)

Orphanet (7): Attenuated familial adenomatous polyposis (Orphanet:220460), Facial dysmorphism-immunodeficiency-livedo-short stature syndrome (Orphanet:352712), Inherited cancer-predisposing syndrome (Orphanet:140162), Cystic fibrosis-gastritis-megaloblastic anemia syndrome (Orphanet:2575), Familial colorectal cancer Type X (Orphanet:440437), Polymerase proofreading-related polyposis (Orphanet:447877), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

showing 60 of 116 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000078	Abnormality of the genital system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000460	Narrow nose
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000505	Visual impairment
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000835	Adrenal hypoplasia
HP:0000938	Osteopenia
HP:0000957	Cafe-au-lait spot
HP:0000964	Eczematoid dermatitis
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:0001402	Hepatocellular carcinoma
HP:0001511	Intrauterine growth retardation
HP:0001824	Weight loss
HP:0002007	Frontal bossing
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002076	Migraine
HP:0002110	Bronchiectasis
HP:0002167	Abnormal speech pattern
HP:0002239	Gastrointestinal hemorrhage
HP:0002354	Memory impairment
HP:0002376	Developmental regression
HP:0002516	Increased intracranial pressure
HP:0002650	Scoliosis
HP:0002653	Bone pain
HP:0002671	Basal cell carcinoma
HP:0002719	Recurrent infections
HP:0002721	Immunodeficiency
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002850	Decreased circulating IgM concentration
HP:0002893	Pituitary adenoma
HP:0002894	Neoplasm of the pancreas

GWAS associations

3 associations:

Study	Trait	p-value
GCST005951_13	Body mass index	6e-9
GCST002829_6	Urate levels in overweight individuals	4e-6
GCST009391_58	Metabolite levels	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004340	body mass index

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C537039	Lubani Al Saleh Teebi syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2363042 (PROTEIN FAMILY)

Clinical evidence (CIViC)

Drug × variant × indication, from 4 curated evidence items; also 4 prognostic, 1 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

4 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
POLE Mutation	Pembrolizumab	Glioblastoma	Sensitivity/Response	CIViC C	EID1861
POLE Mutation	Pembrolizumab	Endometrial Cancer	Sensitivity/Response	CIViC C	EID1862
POLE Mutation	Pembrolizumab	Colorectal Cancer	Sensitivity/Response	CIViC C	EID7469
POLE V411L		Colorectal Cancer	Sensitivity/Response	CIViC C	EID8631

CIViC curated variants (4)

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

P286R (missense variant), V411L (missense variant), S459F (missense variant), Mutation (gene variant).

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	4
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases oxidation, increases abundance, affects cotreatment	1
geraniol	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
aflatoxin B2	increases methylation	1
phenethyl isothiocyanate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases 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
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	increases expression	1
Glyphosate	decreases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	1
Ethanol	decreases expression	1
Arsenic	increases abundance, decreases expression	1
Atrazine	decreases expression	1

Cellosaurus cell lines

40 cell lines: 39 cancer cell line, 1 hybrid cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2529	Ishikawa	Cancer cell line	Female
CVCL_7260	ECC-1	Cancer cell line	Female
CVCL_8783	Ishikawa (London) 02 ER+	Cancer cell line	Female
CVCL_9996	IK-90	Cancer cell line	Female
CVCL_C3G7	Ishikawa 3-H-12 PRA-14	Cancer cell line	Female
CVCL_C3G8	Ishikawa 3-H-12 PRB-59	Cancer cell line	Female
CVCL_C9CC	ISHIKAWA-Luc	Cancer cell line	Female
CVCL_D199	Ishikawa 3-H-12	Cancer cell line	Female
CVCL_F1R3	HyCyte Ishikawa KO-hCTNNBIP1	Cancer cell line	Female
CVCL_F5PN	EDITGENE Ishikawa-Cas9	Cancer cell line	Female

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