POLN
protein-codingDNA polymerase nu, the group of DNA polymerases
Gene summary
This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~170.2 kbGenCC 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 POLN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181808.4. 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 | 2 | 1 | 3 | |||
| missense | 118 | 15 | 2 | 135 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 123 | 16 | 3 | 142 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_861524.2 | 24 | MANE Select | |
| Ensembl | ENSP00000435506.1 | 24 | MANE Select | |
| Ensembl | ENSP00000372316.1 | 24 | Standard | |
| Ensembl | ENSP00000426401.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fanconi anemia pathway - Homo sapiens (human)
- Fanconi Anemia Pathway
- DNA Repair
- Purine metabolism
- Pyrimidine metabolism
Biological Process
- double-strand break repair via homologous recombination
- DNA-dependent DNA replication
- translesion synthesis
- interstrand cross-link repair
Molecular Function
- DNA binding
- DNA-directed DNA polymerase activity
- protein binding
- cyclin binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000511885
- Coding exons
- 24
- Length
- 170204
- Individuals with no LoFs
- 125121
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 627
- Defined
- 125748
- p
- 0.00250
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0475 | 481 | 478 | 1.01 | 0.0000248 | 5872 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0095 | 0.0094 | notable |
| Latino/Admixed American | 0.0016 | 0.0016 | notable |
| Ashkenazi Jewish | 0.0036 | 0.0035 | notable |
| East Asian | 0.0056 | 0.0056 | notable |
| Finnish | 0.0017 | 0.0017 | notable |
| European (Non-Finnish) | 0.0018 | 0.0018 | notable |
| South Asian | 0.0011 | 0.0010 | notable |
| Other | 0.0021 | 0.0021 | notable |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- LoFtool
- 0.543
- RVIS EVS
- 0.65
- RVIS percentile EVS
- 84.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.542
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |