XRN1
protein-coding5'-3' exoribonuclease 1
Gene summary
This gene encodes a member of the 5'-3' exonuclease family. The encoded protein may be involved in replication-dependent histone mRNA degradation, and interacts directly with the enhancer of mRNA-decapping protein 4. In addition to mRNA metabolism, a similar protein in yeast has been implicated in a variety of nuclear and cytoplasmic functions, including homologous recombination, meiosis, telomere maintenance, and microtubule assembly. Mutations in this gene are associated with osteosarcoma, suggesting that the encoded protein may also play a role in bone formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~141.5 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 XRN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001282857.2. 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 | 2 | 1 | 1 | 4 | ||
| missense | 178 | 5 | 183 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 188 | 6 | 1 | 195 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001269786.1 | 41 | MANE Select | |
| Ensembl | ENSP00000376707.2 | 41 | MANE Select | |
| RefSeq | NP_001269788.1 | 12 | Standard | |
| RefSeq | NP_061874.3 | 42 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
- RNA degradation - Homo sapiens (human)
- Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
- Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
- Metabolism of RNA
Biological Process
- nuclear-transcribed mRNA catabolic process
- rRNA catabolic process
- negative regulation of translation
- negative regulation of telomere maintenance via telomerase
- response to testosterone
Molecular Function
- G-quadruplex RNA binding
- RNA binding
- 5'-3' exoribonuclease activity
- protein binding
- G-quadruplex DNA binding
Cellular Component
- P-body
- nucleus
- cytosol
- plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264951
- Coding exons
- 42
- Length
- 141456
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125747
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.11 | 693 | 868 | 0.799 | 0.0000426 | 11251 |
| Missense (PolyPhen) | 83 | 173.71 | 0.4778 | 2202 | ||
| Synonymous | 0.738 | 273 | 289 | 0.945 | 0.0000138 | 3088 |
| Loss of Function | 8.08 | 12 | 98.6 | 0.122 | 0.00000489 | 1272 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00038 | 0.00037 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00014 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Major 5'-3' exoribonuclease involved in mRNA decay. Required for the 5'-3'-processing of the G4 tetraplex-containing DNA and RNA substrates. The kinetic of hydrolysis is faster for G4 RNA tetraplex than for G4 DNA tetraplex and monomeric RNA tetraplex. Binds to RNA and DNA (By similarity). Plays a role in replication-dependent histone mRNA degradation. May act as a tumor suppressor protein in osteogenic sarcoma (OGS). {ECO:0000250|UniProtKB:P97789, ECO:0000269|PubMed:18172165}.;
Recessive Scores
- pRec
- 0.321
Intolerance Scores
- LoFtool
- 0.675
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 30.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.296
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |