DKC1 (dyskeratosis congenita 1, dyskerin)

2002-11-01   Claude Viguié 

Service de Dermatologie, Hôpital Tarnier-Cochin, 89 rue dAssas, 75006 Paris, France

Identity

HGNC
LOCATION
Xq28
IMAGE
Atlas Image
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
FUSION GENES

DNA/RNA

Description

Gene composed of 15 exons (exons 1 and 15 non coding) / 15kb length cDNA 2465 bp (open reading frame between nt 93 and 1637)

Proteins

Expression

widespread tissue expression.

Function

Multifunctional nucleolar protein which associates with H+ACA (hairpin-linge hairpin-tail) class of small nucleolar RNA as its catalytic sub-unit; implicated in centromere function; associated also with the telomerase RNA component; function in ribosome biosynthesis

Homology

highly conserved in eukaryotes: Nap57 (nucleolar associated protein) in the rat, Nop60B in drosophila, Cbf5p (centromere/microtubule binding protein) in yeast. Regional homologies with bacterial Trub proteins and Saccharomyces cerevisiae PUS4 protein.

Implicated in

Disease
Dyskeratosis congenita, X-linked recessive form
Hybrid gene
missense mutation by single-nucleotide substitution at position 1058 in exon 11 (A353V) detected in several different families. Sporadic other missense mutations were detected in exon 3, 4, 10, 12 and in intron 2. Rare deletions and no null mutations are observed.
Fusion protein
non functional protein. It is not presently known how the different mutations affect the protein activity and are responsible of the various phenotypes
Oncogenesis
myelodysplasia and leukemia following bone marrow failure and pancytopenia. Spinocellular carcinoma, other carcinomas of various localization.

Bibliography

Pubmed IDLast YearTitleAuthors
110540582000Dyskeratosis congenita in all its forms.Dokal I et al
109038402000Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1.Heiss NS et al
103645161999X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.Knight SW et al
115748912001The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita.Vulliamy T et al
104387131999Dyskeratosis congenita caused by a 3' deletion: germline and somatic mosaicism in a female carrier.Vulliamy TJ et al

Other Information

Locus ID:

NCBI: 1736
MIM: 300126
HGNC: 2890
Ensembl: ENSG00000130826

Variants:

dbSNP: 1736
ClinVar: 1736
TCGA: ENSG00000130826
COSMIC: DKC1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000130826ENST00000369550O60832
ENSG00000130826ENST00000412124H7BZF2
ENSG00000130826ENST00000413910C9IYT0
ENSG00000130826ENST00000426673H7C2Q2
ENSG00000130826ENST00000437719H7C0M1
ENSG00000130826ENST00000452771H7C2Q9
ENSG00000130826ENST00000620277O60832

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Ribosome biogenesis in eukaryotesKEGGko03008
Ribosome biogenesis in eukaryotesKEGGhsa03008
H/ACA ribonucleoprotein complexKEGGhsa_M00425
H/ACA ribonucleoprotein complexKEGGM00425
Gene ExpressionREACTOMER-HSA-74160
Cell CycleREACTOMER-HSA-1640170
Chromosome MaintenanceREACTOMER-HSA-73886
Telomere MaintenanceREACTOMER-HSA-157579
Extension of TelomeresREACTOMER-HSA-180786
Telomere Extension By TelomeraseREACTOMER-HSA-171319
rRNA processingREACTOMER-HSA-72312
rRNA modification in the nucleus and cytosolREACTOMER-HSA-6790901
rRNA processing in the nucleus and cytosolREACTOMER-HSA-8868773

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
158148782005Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia.239
173958302007Protein composition of catalytically active human telomerase from immortal cells.211
166908642006Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita.173
220993122011rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells.102
245040622014A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia.41
269503712016Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects.40
205018552010Novel dyskerin-mediated mechanism of p53 inactivation through defective mRNA translation.36
197559822009DKC1 overexpression associated with prostate cancer progression.24
214150812011Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita.23
200089002010Effects of dyskeratosis congenita mutations in dyskerin, NHP2 and NOP10 on assembly of H/ACA pre-RNPs.22

Citation

Claude Viguié

DKC1 (dyskeratosis congenita 1, dyskerin)

Atlas Genet Cytogenet Oncol Haematol. 2002-11-01

Online version: http://atlasgeneticsoncology.org/gene/157/dkc1