USB1 Gene: U6 snRNA Biogenesis Phosphodiesterase 1
A key regulator of U6 snRNA processing and its role in poikiloderma with neutropenia and cancer
Gene Information Card
| Symbol | USB1 |
|---|---|
| Full Name | U6 snRNA Biogenesis Phosphodiesterase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q21 |
| NCBI Gene ID | 79650 ncbi.nlm.nih.gov/gene/79650 |
| Ensembl ID | ENSG00000103056 |
| UniProt ID | Q9BQJ4 |
| OMIM ID | 613276 |
| HGNC ID | 25792 |
| Aliases | Clog1, Mpn1, FLJ12666, HSPC111 |
Description
The USB1 gene encodes a 3'-5' exoribonuclease that specifically processes the 3' end of U6 small nuclear RNA (snRNA), a critical component of the spliceosome. It removes the 3' oligo(U) tail generated during U6 snRNA maturation, ensuring proper spliceosome assembly and pre-mRNA splicing. Mutations in USB1 cause poikiloderma with neutropenia (PN), a rare autosomal recessive disorder characterized by skin abnormalities and immune deficiency. The enzyme belongs to the 2H phosphodiesterase superfamily and is also known as Clog1 or Mpn1.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Poikiloderma with neutropenia (PN) | Loss-of-function mutations in USB1 impair U6 snRNA 3' end processing, leading to spliceosome dysfunction and altered gene expression in skin and hematopoietic cells. | OMIM #604173; multiple case reports with biallelic mutations |
| Clonal hematopoiesis / Myelodysplastic syndrome | Somatic mutations in USB1 have been identified in clonal hematopoiesis and MDS, suggesting a role in hematopoietic stem cell maintenance. | COSMIC; ClinVar; PMID: 26026707 |
| Acute myeloid leukemia (AML) | Recurrent somatic mutations in USB1 are found in AML, potentially contributing to leukemogenesis via splicing dysregulation. | COSMIC; PMID: 26026707 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.3 | Medium |
| Skin | 8.7 | Low |
| Spleen | 7.5 | Low |
| Testis | 6.9 | Low |
| Lung | 5.4 | Low |
| Liver | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.2 | Myeloid cell line |
| HEK293 (embryonic kidney) | 10.1 | Common model |
| HeLa (cervical cancer) | 9.3 | Epithelial |
| HepG2 (liver cancer) | 7.8 | Hepatocellular |
| A549 (lung cancer) | 6.5 | Lung epithelial |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.531_532delAT (p.C178Wfs*2) | Frameshift deletion | Reported in PN | Loss of function |
| c.496C>T (p.R166*) | Nonsense | Reported in PN | Loss of function |
| c.307G>A (p.G103S) | Missense | Somatic in AML | Likely loss of function |
| c.425A>G (p.Y142C) | Missense | Somatic in MDS | Unknown |
Mutation functional classification
Loss of Function (LOF)
Most PN-associated mutations are nonsense, frameshift, or missense that abolish enzymatic activity, leading to U6 snRNA 3' end hyperadenylation and spliceosome defects.
Gain of Function (GOF)
No evidence of gain-of-function mutations in USB1.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • RNA phosphodiester bond hydrolysis | • exonucleolytic |
| • U6 snRNA 3'-end processing | • nucleus |
| • cytoplasm | • spliceosomal complex assembly |
Pathways
• mRNA splicing - major pathway
• U6 snRNA maturation
Protein Summary
USB1 is a 3'-5' exoribonuclease that trims the 3' end of U6 snRNA, removing the oligo(U) tail added by the La protein. It is essential for spliceosome recycling and efficient pre-mRNA splicing. The protein localizes to both the nucleus and cytoplasm and contains a 2H phosphodiesterase domain. Loss of function leads to accumulation of aberrant U6 snRNA and splicing errors, particularly affecting genes involved in skin and hematopoiesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USB1 Knockout HEK293 Cell Line | EDJ-KQ16047 | Human | 79650 | Details Get a Quote |
| USB1 Knockout A-549 Cell Line | EDJ-KQ47170 | Human | 79650 | Details Get a Quote |
| USB1 Knockout HCT 116 Cell Line | EDJ-KQ47171 | Human | 79650 | Details Get a Quote |
| USB1 Knockout HeLa Cell Line | EDJ-KQ47172 | Human | 79650 | Details Get a Quote |
