POLE4

protein-coding

DNA polymerase epsilon 4, accessory subunit, the group of DNA polymerases

Gene summary

POLE4 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_019896.4

Inheritance

—

ClinVar variants

U:25B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr2:74,958,643-74,970,128

External References & Databases

Ensembl (ENSG00000115350)

Transcript & Mutation Effects

hg38 • Region Span ~11.5 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 POLE4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 22

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019896.4. 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					1 clinvar	1
missense			22 clinvar			22
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	25	0	1	26

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019896.4	RefSeq	NP_063949.2	4	MANE Select
ENST00000483063.2	Ensembl	ENSP00000420176.1	4	MANE Select
ENST00000871512.1	Ensembl	ENSP00000541571.1	4	Standard
ENST00000871512.2	Ensembl	ENSP00000541571.1	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
histone H3 acetylation
DNA biosynthetic process

Molecular Function

DNA binding
DNA-directed DNA polymerase 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: ENST00000483063
Coding exons: 4
Length: 11637
Individuals with no LoFs: 125474
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125476
p: 0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.330	60	53.2	1.13	0.00000241	703
Missense (PolyPhen)		14	13.002	1.0768		195
Synonymous	-0.413	24	21.6	1.11	0.00000104	241
Loss of Function	0.331	5	5.87	0.852	2.59e-7	70

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in allowing polymerase epsilon to carry out its replication and/or repair function.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.675
RVIS EVS: -0.01
RVIS percentile EVS: 52.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.839

Gene Damage Prediction

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