DKC1

Chr XXLDXLR

dyskerin pseudouridine synthase 1

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

This gene encodes the catalytic subunit of H/ACA small nucleolar ribonucleoprotein complexes that catalyze pseudouridylation of ribosomal RNA and is required for ribosome biogenesis and telomerase maintenance. Mutations cause X-linked dyskeratosis congenita, a multisystem disorder affecting the skin, nails, oral mucosa, bone marrow, and other organs, as well as cataracts, hearing impairment, nephrotic syndrome, and enterocolitis. The gene is highly constrained against loss-of-function variants and follows X-linked inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLD/XLRLOEUF 0.192 OMIM phenotypes
Clinical SummaryDKC1
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Gene-Disease Validity (ClinGen)
DKC1-related disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 0.999
Z-score 4.44
OE 0.04 (0.010.19)
Highly constrained

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

Missense Constraint
3.40Z-score
OE missense 0.33 (0.270.41)
68 obs / 205.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.010.19)
00.351.4
Missense OE0.33 (0.270.41)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 1 / 24.9Missense obs/exp: 68 / 205.0Syn Z: -0.57
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDKC1-related dyskeratosis congenitaLOFXLR
DN
0.3693th %ile
GOF
0.2995th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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