PIF1
protein-codingPIF1 5'-to-3' DNA helicase, the group of DNA helicases
Gene summary
This gene encodes a DNA-dependent adenosine triphosphate (ATP)-metabolizing enzyme that functions as a 5' to 3' DNA helicase. The encoded protein can resolve G-quadruplex structures and RNA-DNA hybrids at the ends of chromosomes. It also prevents telomere elongation by inhibiting the actions of telomerase. Alternative splicing and the use of alternative start codons results in multiple isoforms that are differentially localized to either the mitochondria or the nucleus. [provided by RefSeq, Nov 2013]
- C15orf20
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.0 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 PIF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001286496.2. 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 | 4 | 3 | 8 | ||
| missense | 132 | 7 | 5 | 144 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 137 | 11 | 8 | 156 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001273425.1 | 12 | MANE Select | |
| Ensembl | ENSP00000452792.1 | 12 | MANE Select | |
| RefSeq | NP_001273426.1 | 12 | Standard | |
| RefSeq | NP_001273428.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of Telomerase
Biological Process
- mitochondrial genome maintenance
- telomere maintenance
- DNA replication
- DNA repair
- DNA recombination
Molecular Function
- magnesium ion binding
- ATP binding
- telomerase inhibitor activity
- single-stranded DNA-dependent ATP-dependent DNA helicase activity
- ATP-dependent 5'-3' DNA/RNA helicase activity
Cellular Component
- nuclear chromosome, telomeric region
- replication fork
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268043
- Coding exons
- 12
- Length
- 10037
- Individuals with no LoFs
- 125588
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 160
- Defined
- 125748
- p
- 0.000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.312 | 297 | 313 | 0.950 | 0.0000185 | 3972 |
| Missense (PolyPhen) | 132 | 140.92 | 0.93669 | 1762 | ||
| Synonymous | 1.57 | 109 | 132 | 0.826 | 0.00000740 | 1425 |
| Loss of Function | 0.245 | 25 | 26.4 | 0.948 | 0.00000141 | 282 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00093 | 0.00092 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00051 | 0.00050 | rare |
| South Asian | 0.00075 | 0.00075 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids. Resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. Involved in the maintenance of telomeric DNA. Inhibits telomere elongation, de novo telomere formation and telomere addition to DSBs via catalytic inhibition of telomerase. Reduces the processivity of telomerase by displacing active telomerase from DNA ends. Releases telomerase by unwinding the short telomerase RNA/telomeric DNA hybrid that is the intermediate in the telomerase reaction. Possesses an intrinsic strand annealing activity. {ECO:0000255|HAMAP-Rule:MF_03176, ECO:0000269|PubMed:16522649, ECO:0000269|PubMed:17172855, ECO:0000269|PubMed:17827721, ECO:0000269|PubMed:18835853, ECO:0000269|PubMed:19700773, ECO:0000269|PubMed:20524933, ECO:0000269|PubMed:23657261}.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- LoFtool
- 0.864
- RVIS EVS
- 0.56
- RVIS percentile EVS
- 81.67
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.191
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |