PRIMPOL
protein-codingprimase and DNA directed polymerase, the group of DNA polymerases
Gene summary
This gene encodes a DNA primase-polymerase that belongs to a superfamily of archaeao-eukaryotic primases. Members of this family have primase activity, catalyzing the synthesis of short RNA primers that serve as starting points for DNA synthesis, as well as DNA polymerase activity. The encoded protein facilitates DNA damage tolerance by mediating uninterrupted fork progression after UV irradiation and reinitiating DNA synthesis. An allelic variant in this gene is associated with myopia 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
- CCDC111
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014177
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PRIMPOL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152683.4. 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 | 9 | 9 | ||||
| missense | 86 | 8 | 3 | 97 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 88 | 18 | 3 | 109 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689896.1 | 12 | MANE Select | |
| Ensembl | ENSP00000313816.6 | 12 | MANE Select | |
| RefSeq | NP_001287696.1 | 10 | Standard | |
| RefSeq | NP_001287697.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- mitochondrial DNA replication
- DNA replication, synthesis of RNA primer
- response to UV
- translesion synthesis
- replication fork processing
Molecular Function
- chromatin binding
- DNA-directed DNA polymerase activity
- DNA primase activity
- protein binding
- manganese ion binding
Cellular Component
- nucleus
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314970
- Coding exons
- 12
- Length
- 45351
- Individuals with no LoFs
- 125130
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 614
- Defined
- 125746
- p
- 0.00245
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.299 | 297 | 283 | 1.05 | 0.0000137 | 3705 |
| Missense (PolyPhen) | 97 | 93.992 | 1.032 | 1252 | ||
| Synonymous | 0.244 | 96 | 99.1 | 0.969 | 0.00000478 | 990 |
| Loss of Function | 0.157 | 28 | 28.9 | 0.969 | 0.00000148 | 377 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00081 | 0.00080 | rare |
| Latino/Admixed American | 0.0011 | 0.00098 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.013 | 0.013 | notable |
| Finnish | 0.0013 | 0.0013 | notable |
| European (Non-Finnish) | 0.00077 | 0.00077 | rare |
| South Asian | 0.0067 | 0.0066 | notable |
| Other | 0.0012 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH. {ECO:0000269|PubMed:24126761, ECO:0000269|PubMed:24207056, ECO:0000269|PubMed:24240614, ECO:0000269|PubMed:24267451}.;
- Disease
- DISEASE: Myopia 22, autosomal dominant (MYP22) [MIM:615420]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:23579484}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- RVIS EVS
- 0.51
- RVIS percentile EVS
- 80.24
Essentials
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |