POLK

protein-coding

DNA polymerase kappa, the group of DNA polymerases

Gene summary

This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]

Previous symbols:

DINB1

MANE transcript

NM_016218.6

Inheritance

—

ClinVar variants

P:19U:101B:6

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr5:75,511,845-75,609,991

External References & Databases

Ensembl (ENSG00000122008)

Transcript & Mutation Effects

hg38 • Region Span ~98.1 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 POLK variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 95

Prostate cancerTotal: 20

not providedTotal: 3

SeizureTotal: 1

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016218.6. 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	3 clinvar		1 clinvar	1 clinvar	1 clinvar	6
missense	15 clinvar	1 clinvar	95 clinvar	4 clinvar		115
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	18	1	101	5	1	126

Highest pathogenic variant AF is 0.000020670319

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016218.6	RefSeq	NP_057302.1	14	MANE Select
ENST00000241436.9	Ensembl	ENSP00000241436.4	14	MANE Select
NM_001345921.3	RefSeq	NP_001332850.1	13	Standard
NM_001345922.3	RefSeq	NP_001332851.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fanconi anemia pathway - Homo sapiens (human)
Non-small cell lung cancer - Homo sapiens (human)
Chronic myeloid leukemia - Homo sapiens (human)
Gastric cancer - Homo sapiens (human)
Melanoma - Homo sapiens (human)

Biological Process

DNA replication
DNA repair
transcription-coupled nucleotide-excision repair
nucleotide-excision repair, DNA incision, 5'-to lesion
nucleotide-excision repair, DNA gap filling

Molecular Function

damaged DNA binding
DNA-directed DNA polymerase activity
metal ion binding

Cellular Component

nucleus
nucleoplasm
nuclear body
site of DNA damage

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000241436
Coding exons: 14
Length: 89389
Individuals with no LoFs: 125523
Homozygous LoFs: 0
Heterozygous LoFs: 222
Defined: 125745
p: 0.000883

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.288	416	433	0.961	0.0000203	5815
Missense (PolyPhen)		77	105.44	0.7303		1340
Synonymous	0.0734	142	143	0.992	0.00000664	1522
Loss of Function	2.25	26	41.6	0.624	0.00000223	533

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00059	0.00055	rare
Latino/Admixed American	0.00071	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.0014	0.0013	notable
South Asian	0.00099	0.00088	rare
Other	0.00073	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. {ECO:0000269|PubMed:10620008, ECO:0000269|PubMed:11024016, ECO:0000269|PubMed:12145297, ECO:0000269|PubMed:12444249, ECO:0000269|PubMed:12952891, ECO:0000269|PubMed:14630940, ECO:0000269|PubMed:15533436, ECO:0000269|PubMed:28297716}.;

Recessive Scores

pRec: 0.0864

Intolerance Scores

LoFtool: 0.931
RVIS EVS: -0.57
RVIS percentile EVS: 18.9

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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