POLI
protein-codingDNA polymerase iota, the group of DNA polymerases
Gene summary
The protein encoded by this gene is an error-prone DNA polymerase involved in DNA repair. The encoded protein promotes DNA synthesis across lesions in the template DNA, which other polymerases cannot do. The encoded polymerase inserts deoxynucleotides across lesions and then relies on DNA polymerase zeta to extend the nascent DNA strand to bypass the lesion. [provided by RefSeq, May 2017]
- RAD3OB
- RAD30B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~51.7 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 POLI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007195.3. 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 | 1 | ||||
| missense | 104 | 5 | 109 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 107 | 5 | 0 | 112 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009126.2 | 10 | MANE Select | |
| Ensembl | ENSP00000462664.1 | 10 | MANE Select | |
| RefSeq | NP_001338539.1 | 9 | Standard | |
| RefSeq | NP_001338540.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fanconi anemia pathway - Homo sapiens (human)
- DNA Repair
- Purine metabolism
- Pyrimidine metabolism
- Translesion synthesis by POLI
Biological Process
- DNA replication
- DNA repair
- translesion synthesis
- error-prone translesion synthesis
Molecular Function
- damaged DNA binding
- DNA-directed DNA polymerase activity
- protein binding
- metal ion binding
Cellular Component
- nucleoplasm
- nuclear speck
- cytoplasmic ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000579534
- Coding exons
- 10
- Length
- 51863
- Individuals with no LoFs
- 125483
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 124
- Defined
- 125607
- p
- 0.000494
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.509 | 380 | 353 | 1.08 | 0.0000171 | 4824 |
| Missense (PolyPhen) | 95 | 93.36 | 1.0176 | 1291 | ||
| Synonymous | -0.328 | 128 | 123 | 1.04 | 0.00000577 | 1377 |
| Loss of Function | 1.84 | 16 | 26.1 | 0.612 | 0.00000126 | 408 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0014 | 0.0013 | notable |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.00053 | 0.00051 | rare |
| South Asian | 0.0011 | 0.00065 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Error-prone 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. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity. {ECO:0000269|PubMed:11013228, ECO:0000269|PubMed:11251121, ECO:0000269|PubMed:11387224, ECO:0000269|PubMed:12410315, ECO:0000269|PubMed:14630940, ECO:0000269|PubMed:15199127, ECO:0000269|PubMed:15254543}.;
Recessive Scores
- pRec
- 0.200
Intolerance Scores
- LoFtool
- 0.968
- RVIS EVS
- 0.2
- RVIS percentile EVS
- 67.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.980
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |