POLK

DNA polymerase kappa, the group of DNA polymerases

Basic information

Region (hg38): 5:75511844-75609991

Previous symbols: [ "DINB1" ]

Links

ENSG00000122008 ∙ NCBI:51426 ∙ OMIM:605650 ∙ HGNC:9183 ∙ Uniprot:Q9UBT6 ∙ 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 POLK gene.

• Inborn genetic diseases (25 variants)
• Malignant tumor of prostate (21 variants)
• not provided (3 variants)
• Seizure;Neurodevelopmental delay (1 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLK 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	3			1	1	5
missense	15		25			40
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	1					1
Total	19	0	26	1	1

Highest pathogenic variant AF is 0.0000131

Variants in POLK

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

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

Position	Type	Phenotype	Significance	ClinVar
5-75547050-A-C		not specified	Uncertain significance (Jan 03, 2024)
5-75547106-G-T		not specified	Uncertain significance (Feb 06, 2024)
5-75547107-G-A		Malignant tumor of prostate • Seizure;Neurodevelopmental delay	Conflicting classifications of pathogenicity (Feb 01, 2019)
5-75552473-G-A		not specified	Uncertain significance (Dec 13, 2021)
5-75552506-A-G		not specified	Uncertain significance (Sep 27, 2022)
5-75552545-A-G		not specified	Uncertain significance (Jul 12, 2022)
5-75569484-A-G		not specified	Uncertain significance (Apr 07, 2022)
5-75573739-C-T		Malignant tumor of prostate	Conflicting classifications of pathogenicity (Jan 01, 2019)
5-75573751-A-G		not specified	Uncertain significance (Aug 16, 2022)
5-75573790-G-A		Malignant tumor of prostate	Pathogenic (Feb 05, 2013)
5-75573793-T-C		Malignant tumor of prostate	Pathogenic (Nov 19, 2013)
5-75573841-T-C		Malignant tumor of prostate	Pathogenic (Mar 20, 2013)
5-75576800-T-G		not specified	Uncertain significance (Aug 17, 2022)
5-75576847-A-G		not specified	Uncertain significance (Feb 22, 2023)
5-75581323-A-G		not specified	Uncertain significance (Feb 27, 2023)
5-75581364-G-C		not specified	Uncertain significance (May 16, 2023)
5-75583401-A-G		not specified	Uncertain significance (Mar 31, 2023)
5-75583406-C-T		not specified	Uncertain significance (Apr 27, 2023)
5-75584877-C-T		not specified	Uncertain significance (Jan 19, 2022)
5-75587055-A-G		Malignant tumor of prostate	Pathogenic (Apr 16, 2013)
5-75590345-A-G		not specified	Uncertain significance (Dec 17, 2023)
5-75590368-G-A		Malignant tumor of prostate	Pathogenic (Jan 01, 2013)
5-75590373-A-G		Malignant tumor of prostate	Pathogenic (Jun 10, 2013)
5-75590375-C-A		not specified	Uncertain significance (May 31, 2023)
5-75590408-C-T		Malignant tumor of prostate	Pathogenic (Jun 10, 2014)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLK	protein_coding	protein_coding	ENST00000241436	14	89389

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.47e-13	0.960	125523	0	222	125745	0.000883

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.288	416	433	0.961	0.0000203	5815
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00130	0.00126
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000463	0.000462
European (Non-Finnish)	0.00138	0.00131
Middle Eastern	0.0000544	0.0000544
South Asian	0.000991	0.000882
Other	0.000725	0.000652

dbNSFP

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}.
• Pathway: 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);Small cell lung cancer - Homo sapiens (human);Breast cancer - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Purine metabolism;Pyrimidine metabolism;Translesion synthesis by POLK;Termination of translesion DNA synthesis;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass;Dual Incision in GG-NER;Gap-filling DNA repair synthesis and ligation in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);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: 0.0864

Intolerance Scores

• loftool: 0.931
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.9

Haploinsufficiency Scores

• pHI: 0.139
• hipred: Y
• hipred_score: 0.648
• ghis: 0.613

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polk
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• 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;cellular response to DNA damage stimulus;translesion synthesis;nucleotide-excision repair, DNA incision;cellular response to UV;error-prone translesion synthesis
• Cellular component: nucleus;nucleoplasm;nuclear body;site of DNA damage
• Molecular function: damaged DNA binding;DNA-directed DNA polymerase activity;metal ion binding