POLE3

protein-coding

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

Gene summary

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.[supplied by OMIM, Apr 2004]

MANE transcript

NM_017443.5

Inheritance

—

ClinVar variants

U:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr9:113,407,235-113,410,675

External References & Databases

Ensembl (ENSG00000148229)

Transcript & Mutation Effects

hg38 • Region Span ~3.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POLE3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017443.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			18 clinvar			18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	18	0	0	18

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017443.5	RefSeq	NP_059139.3	4	MANE Select
ENST00000374171.5	Ensembl	ENSP00000363286.4	4	MANE Select
NM_001278255.1	RefSeq	NP_001265184.1	4	Standard
NM_001433719.1	RefSeq	NP_001420648.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

G1/S transition of mitotic cell cycle
DNA replication
cellular response to DNA damage stimulus
CENP-A containing nucleosome assembly
nucleosome mobilization

Molecular Function

DNA binding
DNA-directed DNA polymerase activity
histone acetyltransferase activity
protein binding
protein heterodimerization activity

Cellular Component

nucleus
nucleoplasm
Ada2/Gcn5/Ada3 transcription activator complex
epsilon DNA polymerase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374171
Coding exons: 4
Length: 3438
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125747
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.144	79	82.7	0.956	0.00000422	972
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000098	0.000088	rare
South Asian	0	0.0	absent
Other	0.00033	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.250

Intolerance Scores

LoFtool: 0.507
RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

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