DKC1

Chr X

dyskerin pseudouridine synthase 1

Also known as: CBF5, CHINE1, DKC, DKCX, NAP57, NOLA4, XAP101

NCBI Gene: 1736ENSG00000130826UniProt: O60832

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDyskeratosis congenita, X-linked
UniProtHoyeraal-Hreidarsson syndrome
UniProtCataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1

Clinical highlights

Gene-disease validity (ClinGen)
dyskeratosis congenita, X-linked · XLDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
46
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — DKC1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.19LOEUF
pLI 0.999
Z-score 4.44
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.40Z-score
OE missense 0.33 (0.27–0.41)
68 obs / 205.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.04 (0.01–0.19)
0≤0.351.4
Missense OE?0.33 (0.27–0.41)
0≤0.61.4
Synonymous OE?1.08
0≤1.21.6
LoF obs/exp: 1 / 24.9Missense obs/exp: 68 / 205.0Syn Z: -0.57

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DKC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients