DGUOK

Chr 2AR

deoxyguanosine kinase

Also known as: MTDPS3, NCPH, NCPH1, PEOB4, dGK

The protein phosphorylates purine deoxyribonucleosides in the mitochondrial matrix, which is essential for mitochondrial DNA synthesis and maintenance. Autosomal recessive mutations cause mitochondrial DNA depletion syndrome 3 (hepatocerebral type), progressive external ophthalmoplegia with mitochondrial DNA deletions, and noncirrhotic portal hypertension through dominant negative mechanisms that impair mitochondrial nucleotide metabolism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 1.193 OMIM phenotypes
Clinical SummaryDGUOK
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.000
Z-score 0.99
OE 0.74 (0.471.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.47Z-score
OE missense 1.11 (0.971.26)
165 obs / 148.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.74 (0.471.19)
00.351.4
Missense OE1.11 (0.971.26)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 12 / 16.3Missense obs/exp: 165 / 148.9Syn Z: -0.50
DN
0.76top 25%
GOF
0.5367th %ile
LOF
0.2776th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DGUOK · 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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