DKC1

This gene functions in two distinct complexes. It plays an active role in telomerase stabilization and maintenance, as well as recognition of snoRNAs containing H/ACA sequences which provides stability during biogenesis and assembly into H/ACA small nucleolar RNA ribonucleoproteins (snoRNPs). This gene is highly conserved and widely expressed, and may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion. Mutations have been associated with X-linked dyskeratosis congenita. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Dyskerin Pseudouridine Synthase 1

Isoform 1:
Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674).

This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674).

Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674).

Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534).
Isoform 3:
Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression.

Box H/ACA RNA 3'-end processing Source: GO_Central
Enzyme-directed rRNA pseudouridine synthesis Source: UniProtKB
mRNA pseudouridine synthesis Source: GO_Central
Positive regulation of establishment of protein localization to telomere Source: BHF-UCL
Positive regulation of protein localization to Cajal body Source: BHF-UCL
Positive regulation of telomerase activity Source: BHF-UCL
Positive regulation of telomerase RNA localization to Cajal body Source: BHF-UCL
Positive regulation of telomere maintenance via telomerase Source: Ensembl
Regulation of telomerase RNA localization to Cajal body Source: BHF-UCL
RNA processing Source: ProtInc
rRNA processing Source: ProtInc
rRNA pseudouridine synthesis Source: GO_Central
scaRNA localization to Cajal body Source: BHF-UCL
snRNA pseudouridine synthesis Source: GO_Central
Telomerase RNA stabilization Source: BHF-UCL
Telomere maintenance via telomerase Source: UniProtKB

Isoform 1: Nucleolus; Cajal body. Also localized to Cajal bodies (coiled bodies).
Isoform 3: Cytoplasm

Dyskeratosis congenita, X-linked (DKCX):
The disease is caused by variants affecting the gene represented in this entry. Reduced rRNA pseudouridine levels in cells from patients (PubMed:25219674).
A rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Hoyeraal-Hreidarsson syndrome (HHS):
A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency.