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Official Full Name
chromosome 16 open reading frame 57
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.
C16ORF57; chromosome 16 open reading frame 57; UPF0406 protein C16orf57; FLJ13154; HVSL motif containing 1; HVSL1; poikiloderma with neutropenia; PN

Recent Research Progress

The C16orf57 (USB1) gene is located at 16q21, contains seven exons spanning 22 kb, and encodes a 265-amino acid protein with 5 helical domains that is highly conserved in vertebrates. Although the function of the C16orf57 protein remains unclear, there is evidence that it is critical for the processing and stability of U6 small nucleolar RNA and plays a key role in RNA splicing. Recent studies have confirmed that C16ORF57 mutations may be involved in the pathogenesis of some hereditary skin diseases, such as Poikiloderma with Neutropenia (PN), Dyskeratosis Congenita (DC) and so on.

It is reported that C16orf57 gene mutation may lead to PN

PN is an autosomal recessive genetic skin disease characterized by early onset of neutrophilia, thick nails, hyperkeratosis, skeletal abnormalities and neutropenia, which can lead to abnormal bone marrow hyperplasia. The C16orf57 gene encodes a conserved phosphodiesterase that regulates the stability of the splice U6-RNA. X-ray crystallography of the human C16orf57 protein has clearly demonstrated that C16orf57 is an RNase that trims the 3' end of the U6 transcript, suggesting aberrant oligoadenylation of U6 snRNA in the pathogenesis of PN. Biochemical studies of yeast and lymphoblast cells from PN patients have shown that C16orf57 plays a crucial role in the stability and recycling of the U6 snRNA component of RNA splicing machinery. The defective function of C16orf57 could participate in this pathological mechanism because mutations affecting the splice gene cause defective splicing delineate a new pathway for leukemia. However, splicing defects could only be observed in yeast models, not in PN lymphoblastoid cell lines. Therefore, the pathogenesis of PN needs further study.

C16orf57 mutation is closely related to DC

DC is a rare hereditary disease characterized by reticular skin pigmentation, oral leukoplakia and nail dystrophy. Three genetic models have been recognized: X-linked recessive inheritance (OMIM, 305000), autosomal dominant inheritance (OMIM, 127550), and autosomal recessive inheritance (OMIM, 224230). To date, 10 genes (DKC1, TERC, TERT, TINF2, NOP10, NHP2, TCAB1, C16orf57, and RTEL1) have been identified; 9 of them are important in telomere maintenance. Although the exact function of the C16orf57 gene is still unknown, it may encode proteins involved in ensuring genomic integrity.C16orf57 mutation has been identified in 2% of patients in the DC registry. Sara S et al. analyzed the case of an 8-year-old boy with DC who had childhood idiopathic inflammatory myopathy. The C16orf57 mutation was identified as the genetic cause of DC.

In addition, mutations in C16orf57 appear to be closely related to Rothmund–Thomson syndrome (RTS). Even C16orf57 mutations play an important role in acquired bone marrow tumors. Therefore, further research on the C16orf57 gene and its related diseases is very necessary.


  1. Aude-Annick Suter, et al. Rothmund–Thomson Syndrome: novel pathogenic mutations and frequencies of variants in the RECQL4 and USB1 (C16orf57) gene. Molecular Genetics & Genomic Medicine, 2016, 4(3): 359–366.
  2. Rania Sakka, et al. Poikiloderma with neutropenia in a Tunisian patient with a novel C16orf57 gene mutation. Pediatr Blood Cancer, 2018, 65:e27262.
  3. Elisa A, et al. A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor. Scientific Reports, 2015, 5:15814.
  4. Gloria Negr, et al. Expanding the role of the splicing USB1 gene from Poikiloderma with Neutropenia to acquired myeloid neoplasms. British Journal of Haematology, 2015, 171:557–565.
  5. Sara S et al. Juvenile Idiopathic Inflammatory Myopathy in a Patient with Dyskeratosis Congenita Due to C16orf57 Mutation. Journal Of Pediatric Hematology Oncology, 2016, 38:e75–e77.

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