WRNIP1
protein-codingWRN helicase interacting protein 1, the group of AAA ATPases|Cilia and flagella associated
Gene summary
Werner's syndrome is a rare autosomal recessive disorder characterized by accelerated aging that is caused by defects in the Werner syndrome ATP-dependent helicase gene (WRN). The protein encoded by this gene interacts with the exonuclease-containing N-terminal portion of the Werner protein. This protein has a ubiquitin-binding zinc-finger domain in the N-terminus, an ATPase domain, and two leucine zipper motifs in the C-terminus. It has sequence similarity to replication factor C family proteins and is conserved from E. coli to human. This protein likely accumulates at sites of DNA damage by interacting with polyubiquinated proteins and also binds to DNA polymerase delta and increases the initiation frequency of DNA polymerase delta-mediated DNA synthesis. This protein also interacts with nucleoporins at nuclear pore complexes. Two transcript variants encoding different isoforms have been isolated for this gene. [provided by RefSeq, Jul 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.6 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 WRNIP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020135.3. 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 | 3 | 6 | 9 | |||
| missense | 158 | 1 | 1 | 160 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 163 | 7 | 1 | 171 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064520.2 | 7 | MANE Select | |
| Ensembl | ENSP00000370150.4 | 7 | MANE Select | |
| RefSeq | NP_569079.1 | 7 | Standard | |
| Ensembl | ENSP00000370141.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- DNA synthesis involved in DNA repair
- DNA strand renaturation
- DNA-dependent DNA replication
- regulation of DNA repair
- DNA recombination
Molecular Function
- DNA binding
- protein binding
- ATP binding
- enzyme activator activity
- ATPase activity
Cellular Component
- nuclear chromosome, telomeric region
- nucleus
- membrane
- replisome
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380773
- Coding exons
- 7
- Length
- 21539
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.09 | 382 | 326 | 1.17 | 0.0000177 | 4244 |
| Missense (PolyPhen) | 123 | 121.51 | 1.0122 | 1345 | ||
| Synonymous | -5.09 | 215 | 139 | 1.55 | 0.00000844 | 1333 |
| Loss of Function | 3.04 | 7 | 22.6 | 0.310 | 0.00000135 | 255 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00041 | 0.00040 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a modulator of initiation or reinitiation events during DNA polymerase delta-mediated DNA synthesis. In the presence of ATP, stimulation of DNA polymerase delta-mediated DNA synthesis is decreased. Plays also a role in the innate immune defense against viruses. Stabilizes the RIG-I/DDX58 dsRNA interaction and promotes RIG-I/DDX58 'Lys-63'-linked polyubiquitination. In turn, RIG-I/DDX58 transmits the signal through mitochondrial MAVS. {ECO:0000269|PubMed:15670210, ECO:0000269|PubMed:29053956}.;
Recessive Scores
- pRec
- 0.237
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.927
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |