POLE

Chr 12

DNA polymerase epsilon, catalytic subunit

Also known as: CRCS12, FILS, IMAGEI, POLE1

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. [provided by RefSeq, Sep 2013]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtColorectal cancer 12
UniProtFacial dysmorphism, immunodeficiency, livedo, and short stature
UniProtIntrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency

Clinical highlights

Gene-disease validity (ClinGen)
POLE-related polyposis and colorectal cancer syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
2872
Pubs (1 yr)
P/LP submissions
P/LP missense
0.64
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — POLE
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.64LOEUF
pLI 0.000
Z-score 4.94
OE 0.52 (0.420.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.07Z-score
OE missense 0.92 (0.880.96)
1287 obs / 1399.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.52 (0.420.64)
00.351.4
Missense OE?0.92 (0.880.96)
00.61.4
Synonymous OE?1.05
01.21.6
LoF obs/exp: 64 / 123.1Missense obs/exp: 1287 / 1399.1Syn Z: -1.01

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

POLE · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING
NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14
SunitinibTemsirolimusTrastuzumab and Pertuzumab
Endometrial Cancer

Prevalence of Germline Alterations in Actionable Genes in Endometrial Cancer

NOT YET RECRUITING
NCT07066969Phase NAEuropean Institute of OncologyStarted 2026-01-22
Sophia DDM
Endometrial Cancer, Endometrial Neoplasm

Precision Medicine Applied to the Study of Endometrial Cancer: Application of NGS for Molecular Classification

NOT YET RECRUITING
NCT07006103Hospital Italiano de Buenos AiresStarted 2025-06
Advanced Non-small Cell Lung Cancer, HER2 Mutation

A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)

RECRUITING
NCT06452277Phase PHASE3BayerStarted 2024-08-28
SevabertinibPembrolizumabCisplatin
IGF1 Deficiency

Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).

RECRUITING
NCT00903110Esteve Pharmaceuticals, S.A.Started 2008-12-09
Increlex®
Endometrial Cancer

Improving Endometrial Cancer Assessment by Combining Genomic Profiling and Surgical Assessment

RECRUITING
NCT06354738Phase NAUniversity Hospital, GasthuisbergStarted 2023-01-16
total hysterectomy with bilateral salpingo-oophorectomy, lymph node staging and comprehensive peritoneal staging
Endometrial CancerFertility

Refining Fertility-sparing Treatment in Endometrial Carcinoma Based on Molecular Classification

RECRUITING
NCT07319429Phase PHASE2, PHASE3Fudan UniversityStarted 2026-01-25
PD1 antibodyMedroxyprogesterone Acetate 500 MGMegestrol Acetate 160 MG
High MyopiaPathologic Myopia

Shanghai Child and Adolescent Large-scale Eye Study -High Myopia Registration

ENROLLING BY INVITATION
NCT03666052Shanghai Eye Disease Prevention and Treatment CenterStarted 2018-09-16
Solid TumorAdvanced Solid TumorMetastatic Cancer

KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II

RECRUITING
NCT05525858Seoul National University Bundang HospitalStarted 2022-09-28
AlectinibAtezolizumabErlotinib
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

RECRUITING
NCT03297606Phase PHASE2Canadian Cancer Trials GroupStarted 2018-03-23
OlaparibDasatinibNivolumab plus Ipilimumab
Familial Adenomatous Polyposis (FAP)Attenuated Familial Adenomatous Polyposis (AFAP)MUTYH-Associated Polyposis (MAP)

Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare)

ACTIVE NOT RECRUITING
NCT07461246Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoStarted 2024-05-13
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies