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): 10,987 total — 365 pathogenic, 130 likely-pathogenic
• Phenotypes (HPO): 116
• Druggable target: yes
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006231

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: 25 — 10 retained_intron, 10 nonsense_mediated_decay, 3 protein_coding, 2 protein_coding_CDS_not_defined

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

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.

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

267 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting POLE, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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.

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

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): Q07864, A0A087WW42, A0A087WX51, A0A5F9ZHD6, A0A5F9ZI42, A0A8V8TQH1, A0A8V8TQW1, F5H1D6, F5H7E4

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), 1 shown:

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

UniProt features (183 total): strand 62, helix 44, sequence variant 42, turn 15, 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.

PDB	Method	Resolution (Å)
5VBN	X-RAY DIFFRACTION	2.35
7PLO	ELECTRON MICROSCOPY	2.8
9B8T	ELECTRON MICROSCOPY	2.95
9NE6	ELECTRON MICROSCOPY	3.11
7PFO	ELECTRON MICROSCOPY	3.2
9F6I	ELECTRON MICROSCOPY	3.3
9SRI	ELECTRON MICROSCOPY	3.3
9NE7	ELECTRON MICROSCOPY	3.53
9F6D	ELECTRON MICROSCOPY	3.6
9NE8	ELECTRON MICROSCOPY	3.6
9F6E	ELECTRON MICROSCOPY	3.74
9F6F	ELECTRON MICROSCOPY	3.75
9NEA	ELECTRON MICROSCOPY	3.81
9NE9	ELECTRON MICROSCOPY	3.88
9F6J	ELECTRON MICROSCOPY	3.9
9F6L	ELECTRON MICROSCOPY	3.9
9F6K	ELECTRON MICROSCOPY	4.2
9B8S	ELECTRON MICROSCOPY	5.01

Predicted structure (AlphaFold)

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

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): 2190; 2221; 2224; 2236; 2238; 2158; 2161; 2187

Post-translational modifications (4): 1184, 1297, 1317, 1940

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-68952	DNA replication initiation
R-HSA-68962	Activation of the pre-replicative complex

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

Rollup of top-9 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	2
DNA Damage Bypass	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
Synthesis of DNA	1
DNA Replication Pre-Initiation	1
G1/S Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2945 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLE	POLE2	P56282	989
POLE	POLD1	P28340	988
POLE	POLE4	Q9NR33	964
POLE	POLE3	Q9NRF9	945
POLE	MSH6	P52701	872
POLE	MSH2	P43246	855
POLE	XRCC1	P18887	853
POLE	MLH1	P40692	852
POLE	PMS2	P54278	850
POLE	REV3L	O60673	839
POLE	MUTYH	Q9UIF7	790
POLE	MSH3	P20585	776
POLE	LIG3	P49916	772
POLE	NTHL1	P78549	744
POLE	LIG1	P18858	733

IntAct

125 interactions, top by confidence:

A	B	Type	Score
MMS19	CIAO1	psi-mi:“MI:0914”(association)	0.910
POLE2	POLE	psi-mi:“MI:0915”(physical association)	0.860
POLE	POLE2	psi-mi:“MI:0915”(physical association)	0.860
POLE2	POLE	psi-mi:“MI:0914”(association)	0.860
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
POLE3	POLE2	psi-mi:“MI:0914”(association)	0.690
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
LRRC46	TFPT	psi-mi:“MI:0914”(association)	0.640
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
BRAF	VHL	psi-mi:“MI:0914”(association)	0.600
BRAF	MEN1	psi-mi:“MI:0914”(association)	0.600
POLE	BRAF	psi-mi:“MI:0915”(physical association)	0.600
BRAF	POLE	psi-mi:“MI:0915”(physical association)	0.600
POLE	BRAF	psi-mi:“MI:2364”(proximity)	0.600
ABHD16A	POLE	psi-mi:“MI:0915”(physical association)	0.560
ORF	EIF3F	psi-mi:“MI:0914”(association)	0.560
ORF	EIF3D	psi-mi:“MI:0914”(association)	0.560
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
BMERB1	DCTN6	psi-mi:“MI:0914”(association)	0.530

BioGRID (197): POLE2 (Affinity Capture-MS), POLE (Affinity Capture-MS), POLE (Affinity Capture-MS), POLE (Two-hybrid), POLE (Affinity Capture-MS), POLE (Affinity Capture-MS), MSH6 (Co-fractionation), PABPC1 (Co-fractionation), PABPC4 (Co-fractionation), POLE (Co-fractionation), POLE (Co-fractionation), POLE (Co-fractionation), POLE (Co-fractionation), POLE (Co-fractionation), POLE (Co-fractionation)

ESM2 similar proteins: A7U6F1, A7U6F2, A7U6F3, F4HW04, F4IFN6, O00874, O72539, O89042, O93845, P04415, P05664, P06538, P09252, P09884, P0C971, P0C972, P0C973, P0C974, P0CN26, P0CN27, P10582, P13382, P21951, P27727, P28040, P33609, P42489, P43139, P87154, P87553, Q07864, Q196U0, Q38087, Q4JQU7, Q4PFV5, Q4WXH8, Q54RD4, Q5UQR0, Q65946, Q6BNG2

Diamond homologs: F4HW04, F4IFN6, O93845, P0CN26, P0CN27, P21951, P87154, Q07864, Q4PFV5, Q4WXH8, Q54RD4, Q6BNG2, Q6C4J0, Q6CUS7, Q6FNY7, Q752B8, Q9VCN1, Q9WVF7, O33845, O59610, P30317, P61875, P61876, P0CL76, P0CL77, Q51334, Q9HH06

SIGNOR signaling

1 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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.

GO biological processes:

GO term	Partners	Fold	FDR
T cell costimulation	5	17.3×	4e-03
epidermal growth factor receptor signaling pathway	6	13.8×	4e-03
positive regulation of miRNA transcription	5	13.4×	8e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	11.7×	4e-03
DNA repair	10	5.9×	4e-03

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

10987 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	365
Likely pathogenic	130
Uncertain significance	5424
Likely benign	3710
Benign	140

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1000984	NM_006231.4(POLE):c.2623_2624del (p.Asn875fs)	Pathogenic
1002194	NM_006231.4(POLE):c.3212del (p.Asp1071fs)	Pathogenic
1004888	NM_006231.4(POLE):c.5438dup (p.Tyr1813Ter)	Pathogenic
1006722	NM_006231.4(POLE):c.5957del (p.Leu1986fs)	Pathogenic
1007003	NM_006231.4(POLE):c.6622C>T (p.Gln2208Ter)	Pathogenic
1007208	NM_006231.4(POLE):c.6551_6552del (p.Gln2184fs)	Pathogenic
1007746	NC_000012.11:g.(?133201283)(133263901_?)del	Pathogenic
1008991	NM_006231.4(POLE):c.4221C>G (p.Tyr1407Ter)	Pathogenic
1009020	NM_006231.4(POLE):c.3804G>A (p.Trp1268Ter)	Pathogenic
1009639	NM_006231.4(POLE):c.4309del (p.Ala1437fs)	Pathogenic
1015503	NC_000012.11:g.(?133263830)(133263901_?)del	Pathogenic
1015504	NC_000012.11:g.(?133225505)(133263901_?)del	Pathogenic
1018695	NM_006231.4(POLE):c.3112_3122del (p.Ser1038fs)	Pathogenic
1019088	NM_006231.4(POLE):c.4445-1dup	Pathogenic
1020374	NC_000012.11:g.(?133208891)(133257875_?)del	Pathogenic
1023380	NM_006231.4(POLE):c.5950C>T (p.Gln1984Ter)	Pathogenic
1025545	NM_006231.4(POLE):c.1496_1523del (p.Thr499fs)	Pathogenic
1026192	NM_006231.4(POLE):c.1608dup (p.Glu537Ter)	Pathogenic
1037489	NM_006231.4(POLE):c.821_825del (p.Phe274fs)	Pathogenic
1040225	NM_006231.4(POLE):c.3344_3351del (p.Lys1115fs)	Pathogenic
1040262	NM_006231.4(POLE):c.4138_4139insAGT (p.Ser1380Ter)	Pathogenic
1040669	NM_006231.4(POLE):c.4280_4281del (p.Val1426_Tyr1427insTer)	Pathogenic
1042344	NM_006231.4(POLE):c.104_105del (p.Leu35fs)	Pathogenic
1049585	NM_006231.4(POLE):c.6747+1G>A	Pathogenic
1051606	NM_006231.4(POLE):c.2310del (p.Leu771fs)	Pathogenic
1052126	NM_006231.4(POLE):c.3076dup (p.Asp1026fs)	Pathogenic
1052824	NM_006231.4(POLE):c.5924T>A (p.Leu1975Ter)	Pathogenic
1055819	NM_006231.4(POLE):c.974del (p.Lys325fs)	Pathogenic
1058407	NM_006231.4(POLE):c.1787_1788del (p.Asn595_Phe596insTer)	Pathogenic
1059941	NM_006231.4(POLE):c.1357C>T (p.Gln453Ter)	Pathogenic

SpliceAI

8430 predictions. Top by Δscore:

Variant	Effect	Δscore
12:132624806:AAGAC:A	acceptor_gain	1.0000
12:132624807:AGAC:A	acceptor_gain	1.0000
12:132624808:GAC:G	acceptor_gain	1.0000
12:132624809:AC:A	acceptor_gain	1.0000
12:132624810:CC:C	acceptor_gain	1.0000
12:132624810:CCTG:C	acceptor_loss	1.0000
12:132624811:C:CC	acceptor_gain	1.0000
12:132624811:CTGCA:C	acceptor_loss	1.0000
12:132624815:A:T	acceptor_gain	1.0000
12:132624819:A:AC	acceptor_gain	1.0000
12:132624900:CCCA:C	donor_loss	1.0000
12:132624901:CCA:C	donor_loss	1.0000
12:132624902:CA:C	donor_loss	1.0000
12:132624904:C:CT	donor_loss	1.0000
12:132625641:TCA:T	donor_loss	1.0000
12:132625642:CACCA:C	donor_loss	1.0000
12:132625643:A:AC	donor_gain	1.0000
12:132625643:AC:A	donor_gain	1.0000
12:132625643:ACC:A	donor_loss	1.0000
12:132625644:C:A	donor_loss	1.0000
12:132625644:C:CA	donor_gain	1.0000
12:132625644:CC:C	donor_gain	1.0000
12:132625644:CCA:C	donor_gain	1.0000
12:132625644:CCAG:C	donor_gain	1.0000
12:132625644:CCAGG:C	donor_gain	1.0000
12:132626116:CCT:C	donor_gain	1.0000
12:132626166:CAG:C	donor_gain	1.0000
12:132634181:CTTA:C	donor_loss	1.0000
12:132634183:TA:T	donor_loss	1.0000
12:132634184:A:AG	donor_loss	1.0000

AlphaMissense

15124 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:132657218:A:G	L1167P	1.000
12:132657220:C:A	W1166C	1.000
12:132657220:C:G	W1166C	1.000
12:132657222:A:G	W1166R	1.000
12:132657222:A:T	W1166R	1.000
12:132657365:G:C	P1148R	1.000
12:132657365:G:T	P1148H	1.000
12:132657420:A:G	W1130R	1.000
12:132657420:A:T	W1130R	1.000
12:132659389:C:G	A1061P	1.000
12:132659391:A:G	L1060P	1.000
12:132659394:C:G	R1059P	1.000
12:132661000:G:T	A1010D	1.000
12:132661099:C:T	G977E	1.000
12:132661106:G:T	R975S	1.000
12:132661116:A:C	F971L	1.000
12:132661116:A:T	F971L	1.000
12:132661117:A:G	F971S	1.000
12:132661118:A:G	F971L	1.000
12:132661120:C:T	G970D	1.000
12:132661121:C:G	G970R	1.000
12:132661122:C:A	K969N	1.000
12:132661122:C:G	K969N	1.000
12:132661126:A:G	L968P	1.000
12:132661156:A:T	V958E	1.000
12:132661159:G:T	A957D	1.000
12:132661160:C:G	A957P	1.000
12:132661163:A:G	Y956H	1.000
12:132661164:C:A	R955S	1.000
12:132661164:C:G	R955S	1.000

dbSNP variants (sampled 300 via entrez): RS1000067165 (12:132656008 TA>T,TAA), RS1000106857 (12:132626211 T>A,G), RS1000162996 (12:132675427 C>A,T), RS1000303524 (12:132658440 G>A), RS1000331361 (12:132644701 G>A), RS1000375745 (12:132633364 T>C), RS1000541721 (12:132679386 C>A,T), RS1000555022 (12:132638454 C>T), RS1000587215 (12:132628298 C>A,T), RS1000589630 (12:132679084 C>A,G), RS1000593110 (12:132685961 C>T), RS1000614674 (12:132633504 A>G,T), RS1000655460 (12:132682018 C>T), RS1000832892 (12:132669703 C>T), RS1000855413 (12:132655179 T>C)

Disease associations

OMIM: gene MIM:174762 | disease phenotypes: MIM:615083, MIM:615139, MIM:618336, MIM:114500, MIM:612591, MIM:610965, MIM:219721, MIM:114480

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (1)

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

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

Mondo (28): colorectal cancer, susceptibility to, 12 (MONDO:0014038), hereditary neoplastic syndrome (MONDO:0015356), facial dysmorphism-immunodeficiency-livedo-short stature syndrome (MONDO:0014058), Polymerase proofreading-related adenomatous polyposis (MONDO:0018653), colon carcinoma (MONDO:0002032), intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency (MONDO:0032684), familial ovarian cancer (MONDO:0016248), breast cancer (MONDO:0007254), POLE-related polyposis and colorectal cancer syndrome (MONDO:0100287), familial colorectal cancer type X (MONDO:0018604), colorectal cancer (MONDO:0005575), myoepithelial tumor (MONDO:0002380), colorectal cancer, susceptibility to, 10 (MONDO:0012953), familial colorectal cancer (MONDO:0023113), XFE progeroid syndrome (MONDO:0012590)

Orphanet (11): Attenuated familial adenomatous polyposis (Orphanet:220460), Inherited cancer-predisposing syndrome (Orphanet:140162), Facial dysmorphism-immunodeficiency-livedo-short stature syndrome (Orphanet:352712), Polymerase proofreading-related polyposis (Orphanet:447877), Familial colorectal cancer Type X (Orphanet:440437), Cystic fibrosis-gastritis-megaloblastic anemia syndrome (Orphanet:2575), Intestinal polyposis syndrome (Orphanet:104010), Hereditary breast cancer (Orphanet:227535), OBSOLETE: Familial ovarian cancer (Orphanet:213517), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

116 total (30 of 116 shown, 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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002829_7	Urate levels in overweight individuals	4.000000e-06
GCST005951_3	Body mass index	6.000000e-09
GCST009391_83	Metabolite levels	5.000000e-06

EFO canonical traits (2, from GWAS)

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

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009208	Myoepithelioma	C04.557.435.585
D018302	Neoplasms, Neuroepithelial	C04.557.465.625.600; C04.557.470.670; C04.557.580.625.600
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C562840	Breast Cancer, Familial (supp.)
C537039	Lubani Al Saleh Teebi syndrome (supp.)
C567043	XFE Progeroid Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2363042 (PROTEIN FAMILY)

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 4 curated evidence items; also 3 prognostic, 1 functional.

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

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	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	affects cotreatment, increases expression, increases oxidation, increases abundance	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	affects cotreatment, increases expression	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	decreases expression, increases abundance	1
Atrazine	decreases expression	1

Cellosaurus cell lines

36 cell lines: 35 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_IJ14	Ishikawa-RP	Cancer cell line	Female

Clinical trials (associated diseases)

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

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