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Gene Review

DKC1  -  dyskeratosis congenita 1, dyskerin

Homo sapiens

Synonyms: CBF5, CBF5 homolog, DKC, DKCX, Dyskerin, ...
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Disease relevance of DKC1


Psychiatry related information on DKC1

  • We speculated that mutations in the gene responsible for X-linked DC (DKC1) may account for the HH syndrome, due to the phenotypic similarities between the disease in respect of AA and gender bias [5].

High impact information on DKC1

  • The close homolog Cbf5/dyskerin is the catalytic subunit of box H/ACA snoRNPs [6].
  • Five different missense mutations in five unrelated patients were subsequently identified in XAP101, indicating that it is the gene responsible for X-linked DKC (DKC1) [7].
  • The peptide dyskerin contains two TruB pseudouridine (psi) synthase motifs, multiple phosphorylation sites, and a carboxy-terminal lysine-rich repeat domain [7].
  • The X-linked form of the disease is due to mutations in the gene DKC1 in band 2, sub-band 8 of the long arm of the X chromosome (ref. 3). The affected protein, dyskerin, is a nucleolar protein that is found associated with the H/ACA class of small nucleolar RNAs and is involved in pseudo-uridylation of specific residues of ribosomal RNA [8].
  • Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif [9].

Chemical compound and disease context of DKC1

  • By extrapolation, our findings also support the assignment of pseudouridine synthase function to certain physiologically important eukaryotic proteins that contain Motif I, including the human protein dyskerin, alteration of which leads to the disease dyskeratosis congenita [10].

Biological context of DKC1

  • Mutations in DKC1 mainly lead to amino acid substitutions [11].
  • Dyskerin is therefore thought to function in the processing of pre-rRNA and of the hTR, strengthening the notion that the underlying mechanism of DKC is a premature senescence of cells, especially of the rapidly dividing epithelial and hemopoietic cells [12].
  • We have determined the genomic structure of the DKC1 gene; it consists of 15 exons spanning a region of 15 kb [13].
  • The affected boy had an unaffected brother with the same haplotype around the DKC1 gene and a sister who was heterozygous for the deletion [14].
  • Normal levels of mRNA are produced from the deleted gene, with the transcripts using a cryptic polyadenylation site in the antisense strand of the adjacent MPP1 gene, normally located 1 kb downstream of DKC1 in a tail to tail orientation [14].

Anatomical context of DKC1

  • In addition, higher level Dkc1 expression was confined to embryonic neural tissues as well as to specific neurons in the cerebellum (Purkinje cells) and the olfactory bulb (mitral cells) of the adult brain [12].
  • X-linked dyskeratosis congenita (DC) is a bone marrow failure syndrome caused by mutations in the DKC1 gene located at Xq28 [14].
  • The gene responsible for X-linked DC (DKC1) encodes a highly conserved protein called dyskerin that is believed to be essential in ribosome biogenesis and may also be involved in telomerase RNP assembly [15].
  • Dyskerin gene silencing in the MCF-7 human breast carcinoma cell line reduced telomerase activity and rRNA pseudo-uridylation [4].
  • To test the extent to which disruption of pseudouridylation or telomerase activity may contribute to the pathogenesis of DC, we introduced two dyskerin mutations into murine embryonic stem cells [16].

Associations of DKC1 with chemical compounds

  • Only his mother's DNA was available for mutation analysis, which revealed a nucleotide transition of C to T (1058 C --> T), a hotspot mutation in DKC, resulting in an amino acid change from alanine to valine (A353V) in the DKC1 gene [17].
  • Dyskerin is a putative pseudouridine synthase, and it has been suggested that DKC may be caused by a defect in ribosomal RNA processing [9].
  • Sequencing of the DKC1 gene revealed an inherited missense mutation in base 1050 (GC), changing methionine to isoleucine [18].
  • Dyskerin associates with the H/ACA class of small nucleolar RNAs which are important in guiding the conversion of uracil to pseudouracil in ribosomal RNA [19].

Regulatory relationships of DKC1


Other interactions of DKC1


Analytical, diagnostic and therapeutic context of DKC1


  1. Dyskeratosis congenita: telomerase, telomeres and anticipation. Marrone, A., Walne, A., Dokal, I. Curr. Opin. Genet. Dev. (2005) [Pubmed]
  2. A novel DKC1 mutation, severe combined immunodeficiency (T+B-NK- SCID) and bone marrow transplantation in an infant with Hoyeraal-Hreidarsson syndrome. Cossu, F., Vulliamy, T.J., Marrone, A., Badiali, M., Cao, A., Dokal, I. Br. J. Haematol. (2002) [Pubmed]
  3. Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Yoon, A., Peng, G., Brandenburger, Y., Brandenburg, Y., Zollo, O., Xu, W., Rego, E., Ruggero, D. Science (2006) [Pubmed]
  4. Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer. Montanaro, L., Brigotti, M., Clohessy, J., Barbieri, S., Ceccarelli, C., Santini, D., Taffurelli, M., Calienni, M., Teruya-Feldstein, J., Trerè, D., Pandolfi, P.P., Derenzini, M. J. Pathol. (2006) [Pubmed]
  5. Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1. Knight, S.W., Heiss, N.S., Vulliamy, T.J., Aalfs, C.M., McMahon, C., Richmond, P., Jones, A., Hennekam, R.C., Poustka, A., Mason, P.J., Dokal, I. Br. J. Haematol. (1999) [Pubmed]
  6. Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Hoang, C., Ferré-D'Amaré, A.R. Cell (2001) [Pubmed]
  7. X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Heiss, N.S., Knight, S.W., Vulliamy, T.J., Klauck, S.M., Wiemann, S., Mason, P.J., Poustka, A., Dokal, I. Nat. Genet. (1998) [Pubmed]
  8. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P.J., Dokal, I. Nature (2001) [Pubmed]
  9. A telomerase component is defective in the human disease dyskeratosis congenita. Mitchell, J.R., Wood, E., Collins, K. Nature (1999) [Pubmed]
  10. Functional importance of motif I of pseudouridine synthases: mutagenesis of aligned lysine and proline residues. Spedaliere, C.J., Hamilton, C.S., Mueller, E.G. Biochemistry (2000) [Pubmed]
  11. Dyskeratosis congenita. Marrone, A., Mason, P.J. Cell. Mol. Life Sci. (2003) [Pubmed]
  12. Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1. Heiss, N.S., Bächner, D., Salowsky, R., Kolb, A., Kioschis, P., Poustka, A. Genomics (2000) [Pubmed]
  13. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Knight, S.W., Heiss, N.S., Vulliamy, T.J., Greschner, S., Stavrides, G., Pai, G.S., Lestringant, G., Varma, N., Mason, P.J., Dokal, I., Poustka, A. Am. J. Hum. Genet. (1999) [Pubmed]
  14. Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier. Vulliamy, T.J., Knight, S.W., Heiss, N.S., Smith, O.P., Poustka, A., Dokal, I., Mason, P.J. Blood (1999) [Pubmed]
  15. Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita. Vulliamy, T.J., Knight, S.W., Mason, P.J., Dokal, I. Blood Cells Mol. Dis. (2001) [Pubmed]
  16. Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Mochizuki, Y., He, J., Kulkarni, S., Bessler, M., Mason, P.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  17. DKC1 gene mutation in a Taiwanese kindred with X-linked dyskeratosis congenita. Lin, J.H., Lee, J.Y., Tsao, C.J., Chao, S.C. The Kaohsiung journal of medical sciences. (2002) [Pubmed]
  18. Missense mutation in a patient with X-linked dyskeratosis congenita. Kraemer, D.M., Goebeler, M. Haematologica (2003) [Pubmed]
  19. Dyskeratosis congenita: its link to telomerase and aplastic anaemia. Dokal, I., Vulliamy, T. Blood Rev. (2003) [Pubmed]
  20. Dyskeratosis congenita: a disorder of defective telomere maintenance? Walne, A.J., Marrone, A., Dokal, I. Int. J. Hematol. (2005) [Pubmed]
  21. Analysis of epitope-tagged forms of the dyskeratosis congenital protein (dyskerin): identification of a nuclear localization signal. Youssoufian, H., Gharibyan, V., Qatanani, M. Blood Cells Mol. Dis. (1999) [Pubmed]
  22. Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with Dyskeratosis congenita. Ding, Y.G., Zhu, T.S., Jiang, W., Yang, Y., Bu, D.F., Tu, P., Zhu, X.J., Wang, B.X. J. Invest. Dermatol. (2004) [Pubmed]
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