USB1
protein-codingU6 snRNA biogenesis phosphodiesterase 1
Gene summary
This gene encodes a protein with several conserved domains, however, its exact function is not known. Mutations in this gene are associated with poikiloderma with neutropenia (PN), which shows phenotypic overlap with Rothmund-Thomson syndrome (RTS) caused by mutations in the RECQL4 gene. It is believed that this gene product interacts with RECQL4 protein via SMAD4 proteins, explaining the partial clinical overlap between PN and RTS. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]
- C16orf57
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011405
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0015780
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011405
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0011405
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011405
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Dermatologic
Intervention: Allergy/Immunology/Infectious
Rationale: Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial
Comments: Individuals may also be at risk for leukemia and related processes
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024598.4. 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 | 2 | 136 | 138 | |||
| missense | 1 | 3 | 307 | 13 | 324 | |
| nonsense | 5 | 4 | 9 | |||
| start loss | 4 | 4 | ||||
| frameshift | 10 | 4 | 4 | 18 | ||
| splice donor/acceptor (+/-2bp) | 4 | 5 | 5 | 14 | ||
| Total | 20 | 12 | 326 | 149 | 0 | 507 |
Highest pathogenic variant AF is 0.000031687727
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078874.2 | 7 | MANE Select | |
| Ensembl | ENSP00000219281.3 | 7 | MANE Select | |
| RefSeq | NP_001182231.1 | 6 | Standard | |
| RefSeq | NP_001191840.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usb1 | Danio rerio | Structure: neutrophil Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- RNA splicing
- U6 snRNA 3'-end processing
- RNA phosphodiester bond hydrolysis, exonucleolytic
Molecular Function
- 3'-5'-exoribonuclease activity
- poly(U)-specific exoribonuclease activity, producing 3' uridine cyclic phosphate ends
Cellular Component
- nucleus
- intercellular bridge
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000219281
- Coding exons
- 7
- Length
- 22073
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125748
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.192 | 147 | 154 | 0.956 | 0.00000921 | 1736 |
| Missense (PolyPhen) | 46 | 45.508 | 1.0108 | 526 | ||
| Synonymous | -0.823 | 69 | 60.8 | 1.13 | 0.00000356 | 516 |
| Loss of Function | 1.57 | 7 | 13.2 | 0.532 | 6.56e-7 | 141 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00041 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. {ECO:0000255|HAMAP- Rule:MF_03040, ECO:0000269|PubMed:22899009, ECO:0000269|PubMed:23190533}.;
- Disease
- DISEASE: Poikiloderma with neutropenia (PN) [MIM:604173]: A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-Thomson syndrome. {ECO:0000269|PubMed:20004881, ECO:0000269|PubMed:20503306}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0975
Intolerance Scores
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 67.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |