USB1 gene

U6 snRNA biogenesis phosphodiesterase 1

The USB1 gene provides instructions for making an enzyme that functions as an RNA exonuclease. RNA exonucleases cut off (cleave) building blocks called nucleotides one at a time from molecules of RNA (a chemical cousin of DNA). This process helps stabilize the RNA and protects it from damage.

Specifically, the USB1 enzyme protects a small RNA molecule called U6, which is an essential component of a complex called a spliceosome. The USB1 enzyme also helps transport (chaperones) U6 to the spliceosome and helps it attach (bind) to the proteins in the complex. Spliceosomes process RNA molecules called messenger RNAs (mRNAs) by recognizing and removing regions known as introns and splicing the mRNA molecules back together to provide the blueprint for making proteins.

Different versions (isoforms) of the USB1 enzyme are produced in different tissues, where they play various roles. In blood-forming tissues, the USB1 enzyme is thought to be important for the maturation of neutrophils. Neutrophils are a type of white blood cell involved in the immune system. In the skin, the USB1 enzyme is found in pigment-producing cells (melanocytes), cells in the outer layer of the skin called keratinocytes, and structural cells called fibroblasts. Its role in the function of these cells is unknown.

At least 24 mutations in the USB1 gene have been identified in people with poikiloderma with neutropenia (PN). This condition involves a group of skin abnormalities called poikiloderma and a persistent shortage (deficiency) of neutrophils (chronic neutropenia).

The USB1 gene mutations that cause PN are thought to lead to an enzyme whose function is impaired. As a result of the dysfunctional USB1 exonuclease, the U6 RNA is not protected from damage and not correctly chaperoned to the spliceosomes, leading to impairment of key biological functions. The specific connection between USB1 gene mutations and the signs and symptoms of PN is unknown. However, the existence of tissue-specific isoforms of the enzyme could help explain why this disorder mainly affects the skin and immune system.

Cytogenetic Location: 16q21, which is the long (q) arm of chromosome 16 at position 21

Molecular Location: base pairs 57,999,603 to 58,021,618 on chromosome 16 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 16q21, which is the long (q) arm of chromosome 16 at position 21
  • C16orf57
  • chromosome 16 open reading frame 57
  • hMPN1: mutated in PN1
  • U six biogenesis 1
  • U6 small nuclear RNA biogenesis phosphodiesterase 1
  • U6 snRNA biogenesis 1