POLE3

Summary

POLE3 (DNA polymerase epsilon 3, accessory subunit, HGNC:13546) is a protein-coding gene on chromosome 9q32, encoding DNA polymerase epsilon subunit 3 (Q9NRF9). Accessory component of the DNA polymerase epsilon complex. It is a selective cancer dependency (DepMap: 28.8% of cell lines).

POLE3 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.

Source: NCBI Gene 54107 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 28.8% of screened cell lines
• MANE Select transcript: NM_017443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13546
Approved symbol	POLE3
Name	DNA polymerase epsilon 3, accessory subunit
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	CHRAC17, Ybl1, p17, CHARAC17, CHRAC2
Ensembl gene	ENSG00000148229
Ensembl biotype	protein_coding
OMIM	607267
Entrez	54107

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000374169, ENST00000374171, ENST00000475080, ENST00000479871, ENST00000858453, ENST00000940582

RefSeq mRNA: 3 — MANE Select: NM_017443 NM_001278255, NM_001433719, NM_017443

CCDS: CCDS6795

Canonical transcript exons

ENST00000374171 — 5 exons

Exon	Start	End
ENSE00000983926	113410055	113410140
ENSE00001327295	113410617	113410675
ENSE00001462692	113410228	113410408
ENSE00003533563	113407235	113408983
ENSE00003598088	113409610	113409728

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 96.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.6133 / max 443.1959, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102106	40.6971	1821
102105	1.8255	1065
102108	0.9030	487
102104	0.8069	456
102107	0.3809	161

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.95	gold quality
gastrocnemius	UBERON:0001388	94.45	gold quality
muscle of leg	UBERON:0001383	94.24	gold quality
granulocyte	CL:0000094	94.06	gold quality
monocyte	CL:0000576	93.93	gold quality
leukocyte	CL:0000738	93.85	gold quality
mononuclear cell	CL:0000842	93.80	gold quality
penis	UBERON:0000989	93.75	gold quality
ganglionic eminence	UBERON:0004023	93.73	gold quality
endometrium epithelium	UBERON:0004811	93.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.72	gold quality
rectum	UBERON:0001052	92.59	gold quality
ventricular zone	UBERON:0003053	92.56	gold quality
bone marrow	UBERON:0002371	92.52	gold quality
cerebellar hemisphere	UBERON:0002245	92.49	gold quality
cerebellar cortex	UBERON:0002129	92.47	gold quality
muscle organ	UBERON:0001630	92.36	gold quality
esophagus mucosa	UBERON:0002469	92.33	gold quality
right adrenal gland	UBERON:0001233	92.27	gold quality
right adrenal gland cortex	UBERON:0035827	92.18	gold quality
skin of leg	UBERON:0001511	92.16	gold quality
skin of abdomen	UBERON:0001416	92.14	gold quality
left adrenal gland	UBERON:0001234	92.00	gold quality
lymph node	UBERON:0000029	91.77	gold quality
tibial artery	UBERON:0007610	91.65	gold quality
popliteal artery	UBERON:0002250	91.64	gold quality
cortical plate	UBERON:0005343	91.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.48	gold quality
left adrenal gland cortex	UBERON:0035825	91.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, E2F4, MYC

miRNA regulators (miRDB)

69 targeting POLE3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4261	99.59	70.30	3415

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• We studied the expression profile of the 60 genes located at that genomic region. POLE3 and AKNA were the only two genes deregulated in resistant tumors harboring the 9q32-q33.1 gain (PMID:29618620)
• iochemical analyses establish that POLE3-POLE4 is a histone chaperone that promotes tetrasome formation and DNA supercoiling in vitro. In cells, POLE3-POLE4 binds both newly synthesized and parental histones, and its depletion hinders helicase unwinding and chromatin PCNA unloading and compromises coordinated parental histone retention and new histone deposition (PMID:30217558)
• Loss of POLE3-POLE4 unleashes replicative gap accumulation upon treatment with PARP inhibitors. (PMID:38753485)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pole3	ENSMUSG00000028394
rattus_norvegicus	Pole3	ENSRNOG00000004843
rattus_norvegicus	Pole3	ENSRNOG00000070688

Protein

Protein identifiers

DNA polymerase epsilon subunit 3 — Q9NRF9 (reviewed: Q9NRF9)

Alternative names: Arsenic-transactivated protein, Chromatin accessibility complex 17 kDa protein, DNA polymerase II subunit 3, DNA polymerase epsilon subunit p17

All UniProt accessions (1): Q9NRF9

UniProt curated annotations — full annotation on UniProt →

Function. Accessory component of the DNA polymerase epsilon complex. Participates in DNA repair and in chromosomal DNA replication. Forms a complex with CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1. Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex.

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. Interaction with POLE4 is a prerequisite for further binding with POLE and POLE2. Heterodimer with CHRAC1; binds to DNA. Component of the CHRAC ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H, BAZ1A/ACF1, CHRAC1 and POLE3; the complex preferentially binds DNA through the CHRAC1-POLE3 heterodimer and possesses ATP-dependent nucleosome-remodeling activity. Within the complex, the heterodimer with CHRAC1 interacts with SMARCA5/SNF2H; the interaction is direct and enhances nucleosome sliding activity by the SMARCA5/SNF2H and BAZ1A/ACF1 interaction. Within the complex, the heterodimer with CHRAC1 interacts with BAZ1A/ACF1; the interactions are direct.

Subcellular location. Nucleus.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

RefSeq proteins (3): NP_001265184, NP_001420648, NP_059139* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003958	CBFA_NFYB_domain	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR051377	DNA_Pol-Epsilon_Subunit	Family

Pfam: PF00808

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

UniProt features (15 total): sequence variant 3, sequence conflict 3, modified residue 3, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRF9-F1	85.72	0.58

Functional residue map

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

Post-translational modifications (3): 2, 83, 122

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: 300 (showing top): MORF_MTA1, REACTOME_DNA_REPLICATION, MORF_SMC1L1, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_DNA_STRAND_ELONGATION_INVOLVED_IN_DNA_REPLICATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MORF_HDAC1, MORF_UBE2N, MORF_RAD21, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MORF_HDAC2, KAUFFMANN_DNA_REPAIR_GENES, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA replication (GO:0006260), DNA-templated DNA replication (GO:0006261), leading strand elongation (GO:0006272), regulation of DNA replication (GO:0006275), nucleosome assembly (GO:0006334), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974), heterochromatin formation (GO:0031507), DNA biosynthetic process (GO:0071897)

GO Molecular Function (5): DNA-directed DNA polymerase activity (GO:0003887), chromatin DNA binding (GO:0031490), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), epsilon DNA polymerase complex (GO:0008622), CHRAC (GO:0008623), ATAC complex (GO:0140672), chromatin (GO:0000785)

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	2
DNA replication	2
chromatin organization	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA biosynthetic process	1
DNA replication, synthesis of primer	1
DNA strand elongation involved in DNA replication	1
DNA replication, removal of RNA primer	1
regulation of DNA metabolic process	1
nucleosome organization	1
protein-DNA complex assembly	1
cellular response to stress	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
nucleic acid biosynthetic process	1
DNA polymerase activity	1
DNA binding	1
chromatin binding	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome, centromeric region	1
heterochromatin	1
nuclear chromosome	1
DNA polymerase complex	1
nuclear protein-containing complex	1
ISWI-type complex	1
SAGA-type complex	1
chromosome	1

Protein interactions and networks

STRING

1528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLE3	CHRAC1	Q9NRG0	998
POLE3	POLE4	Q9NR33	998
POLE3	POLE2	P56282	994
POLE3	BAZ1A	Q9NRL2	986
POLE3	SMARCA5	O60264	958
POLE3	POLE	Q07864	945
POLE3	SMARCA1	P28370	878
POLE3	NFYC	Q13952	728
POLE3	POLD1	P28340	726
POLE3	BAZ1B	Q9UIG0	699
POLE3	POLA2	Q14181	689
POLE3	POLA1	P09884	688
POLE3	POLD2	P49005	682
POLE3	RSF1	Q96T23	678
POLE3	MBIP	Q9NS73	671

IntAct

63 interactions, top by confidence:

A	B	Type	Score
POLE2	POLE	psi-mi:“MI:0914”(association)	0.860
POLE3	DRAP1	psi-mi:“MI:0915”(physical association)	0.830
POLE3	CHRAC1	psi-mi:“MI:0915”(physical association)	0.830
CHRAC1	POLE3	psi-mi:“MI:0915”(physical association)	0.830
DRAP1	POLE3	psi-mi:“MI:0915”(physical association)	0.830
POLE3	DR1	psi-mi:“MI:0915”(physical association)	0.780
DR1	POLE3	psi-mi:“MI:0915”(physical association)	0.780
POLE4	POLE3	psi-mi:“MI:0915”(physical association)	0.770
POLE3	POLE2	psi-mi:“MI:0914”(association)	0.690
POLE2	POLE4	psi-mi:“MI:0914”(association)	0.640
POLE3	DKFZp666G145	psi-mi:“MI:0915”(physical association)	0.560
DKFZp666G145	POLE3	psi-mi:“MI:0915”(physical association)	0.560
POLE2	CYP4F12	psi-mi:“MI:0914”(association)	0.560
ORF	EIF3F	psi-mi:“MI:0914”(association)	0.560

BioGRID (157): POLE3 (Two-hybrid), POLE3 (Two-hybrid), CHRAC1 (Two-hybrid), POLE3 (Affinity Capture-RNA), POLE3 (Affinity Capture-RNA), POLE3 (Affinity Capture-RNA), POLE3 (Two-hybrid), POLE3 (Two-hybrid), ATAD2 (Co-fractionation), POLE (Co-fractionation), POLE3 (Co-fractionation), POLE3 (Co-fractionation), POLE3 (Co-fractionation), POLE3 (Co-fractionation), POLE3 (Co-fractionation)

ESM2 similar proteins: A1ZAX1, B0Y0F3, B3MIF1, B3NML0, B3S3D5, B4GIB1, B4HMY3, B4KN00, B4LNA1, B4MRZ8, O04027, O13472, O14311, O14348, O17453, O23310, P06844, P13434, P36611, P40096, P55034, Q04603, Q28Z41, Q3SYW6, Q3SZN5, Q4WFF8, Q55DJ5, Q5R4W3, Q642A5, Q6C6M5, Q6CHS6, Q6NQH4, Q6NRI8, Q6NXC0, Q75JQ9, Q7K3D8, Q8L7N3, Q92317, Q99MP8, Q9D084

Diamond homologs: O04027, O14348, O17286, O23310, O82248, P13434, P25207, P25208, P25209, P25210, P25211, P36611, P40914, P63139, P63140, Q01658, Q0J7P4, Q32KW0, Q3SZN5, Q54WV0, Q5QMG3, Q5R4W3, Q5XI68, Q5ZMV3, Q60EQ4, Q642A5, Q65XK1, Q67XJ2, Q69J40, Q6RG77, Q6Z348, Q75IZ7, Q84W66, Q8VYK4, Q91WV0, Q9FGJ3, Q9JKP7, Q9NRF9, Q9SFD8, Q9SIT9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLE3	“form complex”	“DNA polymerase epsilon”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
nucleosome assembly	5	21.3×	3e-04
chromatin remodeling	5	11.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

340 predictions. Top by Δscore:

Variant	Effect	Δscore
9:113408979:ATATG:A	acceptor_gain	1.0000
9:113408980:TATG:T	acceptor_gain	1.0000
9:113408981:ATG:A	acceptor_gain	1.0000
9:113408982:TG:T	acceptor_gain	1.0000
9:113408983:GC:G	acceptor_loss	1.0000
9:113408984:C:CA	acceptor_loss	1.0000
9:113408984:C:CC	acceptor_gain	1.0000
9:113409604:CGTTA:C	donor_loss	1.0000
9:113409605:GTTAC:G	donor_loss	1.0000
9:113409606:TTA:T	donor_loss	1.0000
9:113409607:TAC:T	donor_loss	1.0000
9:113409609:C:T	donor_loss	1.0000
9:113409612:T:A	donor_gain	1.0000
9:113409724:TAGCA:T	acceptor_gain	1.0000
9:113409725:AGCA:A	acceptor_gain	1.0000
9:113409726:GCA:G	acceptor_gain	1.0000
9:113409727:CA:C	acceptor_gain	1.0000
9:113409727:CAC:C	acceptor_gain	1.0000
9:113409727:CACTG:C	acceptor_loss	1.0000
9:113409728:AC:A	acceptor_loss	1.0000
9:113409729:C:CC	acceptor_gain	1.0000
9:113409730:T:C	acceptor_loss	1.0000
9:113410049:GCTCA:G	donor_loss	1.0000
9:113410051:TCA:T	donor_loss	1.0000
9:113410052:CACCA:C	donor_loss	1.0000
9:113410053:A:AC	donor_gain	1.0000
9:113410054:C:CC	donor_gain	1.0000
9:113410054:CCAGG:C	donor_gain	1.0000
9:113410141:C:CC	acceptor_gain	1.0000
9:113410222:GCTCA:G	donor_loss	1.0000

AlphaMissense

985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:113409666:G:T	A72D	1.000
9:113409699:C:G	R61P	1.000
9:113409726:G:T	A52D	1.000
9:113409727:C:G	A52P	1.000
9:113410064:G:T	A48D	1.000
9:113410065:C:G	A48P	1.000
9:113410070:A:G	L46P	1.000
9:113410085:G:T	A41D	1.000
9:113410086:C:G	A41P	1.000
9:113410088:G:T	A40D	1.000
9:113410089:C:G	A40P	1.000
9:113410244:C:A	R17M	1.000
9:113410256:G:T	A13D	1.000
9:113410262:G:A	P11L	1.000
9:113410262:G:T	P11H	1.000
9:113410265:A:T	L10Q	1.000
9:113410271:A:G	L8P	1.000
9:113409615:A:G	L89P	0.999
9:113409627:A:C	L85W	0.999
9:113409667:C:G	A72P	0.999
9:113409675:A:T	V69E	0.999
9:113409678:T:A	D68V	0.999
9:113409678:T:C	D68G	0.999
9:113409679:C:A	D68Y	0.999
9:113409697:T:C	K62E	0.999
9:113409714:G:T	A56E	0.999
9:113409715:C:G	A56P	0.999
9:113410059:A:G	S50P	0.999
9:113410070:A:T	L46Q	0.999
9:113410073:A:T	V45E	0.999

dbSNP variants (sampled 300 via entrez): RS1000276581 (9:113411362 G>A,C), RS1000857194 (9:113407345 T>C), RS1001562761 (9:113407093 T>A), RS1001844529 (9:113410736 C>A,T), RS1002178653 (9:113412498 GAA>G), RS1002481002 (9:113412137 A>T), RS1002813448 (9:113410767 G>A), RS1003958612 (9:113407386 G>A,C), RS1004753016 (9:113411903 C>G), RS1004994728 (9:113407616 G>A), RS1005104341 (9:113412039 T>C), RS1005316043 (9:113410086 C>T), RS1005526300 (9:113411898 G>C), RS1005974881 (9:113412104 G>C), RS1006365419 (9:113410902 C>G,T)

Disease associations

OMIM: gene MIM:607267 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363042 (PROTEIN FAMILY), CHEMBL3833525 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.59	Kd	25.76	nM	CHEMBL5653589
7.30	ED50	49.95	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149031: Binding affinity to human POLE3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0258	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases methylation, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	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 expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	increases expression	1
K 7174	decreases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
pyrimidifen	increases expression	1
abrine	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Antimycin A	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5052917	Binding	Binding affinity towards wild-type POLE3 overexpressed in human 293T cells measured after 1 hr by SDS-PAGE analysis	Novel sesquiterpenoid analogs

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3E7	Abcam HEK293T POLE3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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