POLN

DNA polymerase nu, the group of DNA polymerases

Basic information

Region (hg38): 4:2071917-2242121

Links

ENSG00000130997 ∙ NCBI:353497 ∙ OMIM:610887 ∙ HGNC:18870 ∙ Uniprot:Q7Z5Q5 ∙ 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 POLN gene.

• Inborn genetic diseases (65 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLN 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			35	5	2	42
nonsense						0
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			26			26
Total	0	0	61	5	3

Variants in POLN

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

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

Position	Type	Phenotype	Significance	ClinVar
4-2072130-G-A		not specified	Uncertain significance (Jun 30, 2023)
4-2072170-A-T		not specified	Uncertain significance (Jan 08, 2024)
4-2072203-C-G		not specified	Uncertain significance (May 25, 2023)
4-2072230-C-T		not specified	Uncertain significance (Jul 30, 2023)
4-2072975-TG-T			Benign (Jan 18, 2019)
4-2072981-T-A		not specified	Uncertain significance (Dec 22, 2023)
4-2073010-C-T		not specified	Uncertain significance (Jun 30, 2023)
4-2073026-A-T		not specified	Uncertain significance (Feb 10, 2022)
4-2075463-G-A		not specified	Uncertain significance (Jul 06, 2022)
4-2075515-C-T		not specified	Uncertain significance (Jan 08, 2024)
4-2081674-C-T		Malignant tumor of prostate	Uncertain significance (-)
4-2081690-G-C		not specified	Uncertain significance (Jan 26, 2022)
4-2085646-C-T		not specified	Uncertain significance (Oct 13, 2023)
4-2085672-T-G		not specified	Uncertain significance (Jul 06, 2022)
4-2085677-A-C			Benign (Dec 31, 2019)
4-2095859-T-C		not specified	Uncertain significance (Aug 12, 2021)
4-2095868-G-A			Likely benign (Sep 01, 2022)
4-2095902-C-T		not specified	Uncertain significance (Jan 22, 2024)
4-2095912-C-G		not specified	Likely benign (Nov 09, 2021)
4-2095931-T-G		not specified	Uncertain significance (Feb 15, 2023)
4-2128126-G-C		not specified	Uncertain significance (Apr 04, 2023)
4-2128129-T-C		not specified	Uncertain significance (Feb 26, 2024)
4-2128131-G-A		not specified	Uncertain significance (Jan 26, 2022)
4-2128206-C-T		not specified	Uncertain significance (Dec 14, 2021)
4-2128216-T-C		not specified	Uncertain significance (Oct 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLN	protein_coding	protein_coding	ENST00000511885	24	170204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.49e-41	8.74e-8	125121	0	627	125748	0.00250

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0475	481	478	1.01	0.0000248	5872
Missense in Polyphen		116	127.67	0.90858		1698
Synonymous	0.846	168	183	0.920	0.0000102	1711
Loss of Function	-0.927	57	49.9	1.14	0.00000244	608

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0112	0.0110
Ashkenazi Jewish	0.00357	0.00348
East Asian	0.00565	0.00562
Finnish	0.00173	0.00171
European (Non-Finnish)	0.00177	0.00176
Middle Eastern	0.00565	0.00562
South Asian	0.00106	0.00105
Other	0.00213	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA polymerase with very low fidelity that catalyzes considerable misincorporation by inserting dTTP opposite a G template, and dGTP opposite a T template (PubMed:16787914, PubMed:17118716). Is the least accurate of the DNA polymerase A family (i.e. POLG, POLN and POLQ) (PubMed:17118716). Can perform accurate translesion DNA synthesis (TLS) past a 5S-thymine glycol. Can perform efficient strand displacement past a nick or a gap and gives rise to an amount of product similar to that on non-damaged template. Has no exonuclease activity (PubMed:16787914). Error- prone DNA polymerase that preferentially misincorporates dT regardless of template sequence (PubMed:25775266). May play a role in TLS during interstrand cross-link (ICL) repair (PubMed:19908865). May be involved in TLS when genomic replication is blocked by extremely large major groove DNA lesions. May function in the bypass of some DNA-protein and DNA-DNA cross- links. May have a role in cellular tolerance to DNA cross-linking agents (PubMed:20102227). Involved in the repair of DNA cross- links and double-strand break (DSB) resistance. Participates in FANCD2-mediated repair. Forms a complex with HELQ helicase that participates in homologous recombination (HR) repair and is essential for cellular protection against DNA cross-links (PubMed:19995904). {ECO:0000269|PubMed:16787914, ECO:0000269|PubMed:17118716, ECO:0000269|PubMed:19908865, ECO:0000269|PubMed:19995904, ECO:0000269|PubMed:20102227, ECO:0000269|PubMed:25775266}.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;Purine metabolism;Pyrimidine metabolism (Consensus)

Intolerance Scores

• loftool: 0.543
• rvis_EVS: 0.65
• rvis_percentile_EVS: 84.18

Haploinsufficiency Scores

• pHI: 0.0656
• hipred: N
• hipred_score: 0.457
• ghis: 0.503

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.542

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Poln
• Phenotype: cellular phenotype; normal phenotype; reproductive system phenotype

Gene ontology

• Biological process: double-strand break repair via homologous recombination;DNA-dependent DNA replication;translesion synthesis;interstrand cross-link repair
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm
• Molecular function: DNA binding;DNA-directed DNA polymerase activity;protein binding;cyclin binding