Alt. symbols: DKC | XAP101 | dyskerin | NAP57 | NOLA4 | Cbf5

Approved name: dyskerin pseudouridine synthase 1
Alt. names: dyskeratosis congenita 1, dyskerin | H/ACA ribonucleoprotein complex subunit 4

Location: Xq28: 154762742 - 154777689 (+)
Gene type: protein_coding, 32 transcripts.

Scores: LoFtool: | pLI: 0.99890017 | LOEUF: 0.191

HGNC: 2890

NCBI: 1736, RefSeq: NG_009780.1

Ensembl: ENSG00000130826.19

LRG_55 | Status: public

OMIM: 300126

Expression | ProteinAtlas

DKC1 encodes the H/ACA ribonucleoprotein complex subunit 4 known as dyskerin. This gene functions in two different 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.

Hemizygous mutations in the gene cause x-linked dyskeratosis congenita [MIM:305000]. Among the genes associated with telomeropathies, mutations in RTEL1 or TERT are the most frequently reported, however the highest number of pathogenic (or probably pathogenic) mutations are observed in the DKC1 gene (PMID:32930426). There are currently almost 90 different mutations reported to ClinVar, and more than 40 are considered pathogenic or likely pathogenic. Virtually all reported mutations to date are m issense, although a 2-Kb deletion, a promoter mutation, and a couple of splice-site mutations have also been reported. It is thought that these sequence changes probably interfere dyskerin's ability to bind to hTR (part of the telomerase complex), resulting in dysfunction of the whole complex. Telomerase dysfunction prevents the normal maintenance of telomeres and leads to reduced telomere length. Rapidly diving cells, such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow, are specially affected by the effects of shortened telomeres. Inadequate telomere maintenance may also result in the development of cancer in some patients. [Load More]