POLE3

DNA polymerase epsilon 3, accessory subunit, the group of Chromatin accessibility complex|ATAC complex|DNA polymerases

Basic information

Region (hg38): 9:113407234-113410675

Links

ENSG00000148229 ∙ NCBI:54107 ∙ OMIM:607267 ∙ HGNC:13546 ∙ Uniprot:Q9NRF9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLE3 gene.

• Inborn genetic diseases (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLE3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	7	0	0

Variants in POLE3

This is a list of pathogenic ClinVar variants found in the POLE3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-113408843-C-G		not specified	Uncertain significance (Feb 01, 2023)
9-113408864-C-T		not specified	Uncertain significance (Aug 13, 2021)
9-113408892-C-A		not specified	Uncertain significance (Sep 17, 2021)
9-113408924-C-T		not specified	Uncertain significance (Dec 11, 2023)
9-113408974-C-A		not specified	Uncertain significance (Aug 02, 2023)
9-113410107-G-A		not specified	Uncertain significance (Jun 30, 2022)
9-113410128-C-T		not specified	Uncertain significance (Aug 16, 2022)
9-113410136-G-A		not specified	Uncertain significance (Sep 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLE3	protein_coding	protein_coding	ENST00000374171	4	3438

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0307	0.823	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.144	79	82.7	0.956	0.00000422	972
Missense in Polyphen		24	27.605	0.8694		315
Synonymous	-0.699	39	33.8	1.15	0.00000178	251
Loss of Function	1.13	3	5.99	0.501	2.50e-7	81

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000981	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000326	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Forms a complex with DNA polymerase epsilon subunit CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Pyrimidine metabolism - Homo sapiens (human);Base excision repair - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);DNA replication - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Pyrimidine metabolism;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Purine metabolism;Activation of the pre-replicative complex;Mitotic G1-G1/S phases;DNA replication initiation;DNA Replication;Pyrimidine metabolism;Synthesis of DNA;S Phase;PCNA-Dependent Long Patch Base Excision Repair;Resolution of AP sites via the multiple-nucleotide patch replacement pathway;Resolution of Abasic Sites (AP sites);Base Excision Repair;Telomere C-strand synthesis initiation;Telomere C-strand (Lagging Strand) Synthesis;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;G1/S Transition;Recognition of DNA damage by PCNA-containing replication complex;DNA Replication Pre-Initiation;M/G1 Transition;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Cell Cycle;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• loftool: 0.507
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.54

Haploinsufficiency Scores

• pHI: 0.347
• hipred: Y
• hipred_score: 0.774
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pole3

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;cellular response to DNA damage stimulus;CENP-A containing nucleosome assembly;nucleosome mobilization;histone H3 acetylation;heterochromatin assembly involved in chromatin silencing;cellular response to gamma radiation;DNA biosynthetic process
• Cellular component: nucleus;nucleoplasm;Ada2/Gcn5/Ada3 transcription activator complex;epsilon DNA polymerase complex
• Molecular function: DNA binding;DNA-directed DNA polymerase activity;histone acetyltransferase activity;protein binding;protein heterodimerization activity