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DGUOK

deoxyguanosine kinase

The DGUOK gene encodes the deoxyguanosine kinase enzyme, which is essential for maintaining mitochondrial DNA and plays a vital role in cellular energy production. The DGUOK gene provides the blueprint for deoxyguanosine kinase, an enzyme critical for the health and function of mitochondria.

Chromosome 2p13.1 Autosomal recessive HGNC:2858 Tier C
DGUOK 2p13.1 p arm q arm 2

DGUOK is located on the short (p) arm of chromosome 2, at band 2p13.1. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
DGUOK is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The DGUOK gene, also known as deoxyguanosine kinase, provides instructions for creating an enzyme of the same name. This enzyme is primarily active within mitochondria, the cellular organelles responsible for producing most of the cell's energy. Deoxyguanosine kinase plays a crucial role in maintaining the integrity and function of mitochondrial DNA (mtDNA), which is vital for normal mitochondrial operation. Inherited changes within the DGUOK gene can lead to conditions characterised by impaired mitochondrial function.

What the gene does

The deoxyguanosine kinase enzyme, encoded by the DGUOK gene, is centrally involved in the metabolism of nucleosides within mitochondria. Specifically, it phosphorylates deoxyguanosine and other deoxyribonucleosides, converting them into their active triphosphate forms. These triphosphate forms are the essential building blocks required for the synthesis and repair of mitochondrial DNA. By facilitating the production and maintenance of mtDNA, the DGUOK enzyme indirectly supports the efficient functioning of the electron transport chain, which is key to cellular energy production through oxidative phosphorylation.

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Chromosome location

The DGUOK gene is situated on the short arm of chromosome 2, specifically at position 2p13.1. This genomic location indicates its precise address within the human genome. The gene spans a specific region on this chromosome, contributing to its overall organisation.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Genetic variations, or variants, in the DGUOK gene can disrupt the normal production or function of the deoxyguanosine kinase enzyme. Many identified variants involve changes to single amino acids within the enzyme, which can alter its structure and activity. Other types of variants may lead to the production of a truncated, non-functional protein, ultimately impairing mitochondrial DNA maintenance and cellular energy production.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for DGUOK.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.155C>T
single nucleotide variant
 p.Ser52Phe Pathogenic/Likely pathogenic ★★☆☆ DGUOK-related disorder
c.195G>A
single nucleotide variant
 p.Trp65Ter Pathogenic ★★☆☆ Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
c.235C>T
single nucleotide variant
 p.Gln79Ter Pathogenic ★★☆☆ Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4
c.352C>T
single nucleotide variant
 p.Arg118Cys Pathogenic/Likely pathogenic ★★☆☆ Inborn genetic diseases
c.443+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ not provided
c.444-62C>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ DGUOK-related disorder
c.493G>A
single nucleotide variant
 p.Glu165Lys Pathogenic/Likely pathogenic ★★☆☆ Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
c.494A>T
single nucleotide variant
 p.Glu165Val Pathogenic/Likely pathogenic ★★☆☆ Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
c.592-4_592-3del
Deletion
 - Pathogenic/Likely pathogenic ★★☆☆ Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
c.677A>G
single nucleotide variant
 p.His226Arg Pathogenic ★★☆☆ DGUOK-related disorder

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the DGUOK gene are associated with deoxyguanosine kinase deficiency. This inherited disorder can manifest with diverse clinical features, primarily affecting organs with high energy demands such as the liver, muscles, and brain. Conditions such as progressive external ophthalmoplegia are also linked to DGUOK gene changes, reflecting its role in mitochondrial health.

No disease links recorded for this gene in our reference set.

Inheritance pattern

Conditions caused by pathogenic DGUOK variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous DGUOK carrier status across ancestry groups?

UK clinical status

The DGUOK gene is included in several NHS PanelApp green-lighted panels, indicating strong evidence for its association with specific conditions in a UK clinical context. These panels include Acute rhabdomyolysis, Cholestasis, Ductal plate malformation, Inherited white matter disorders, Likely inborn error of metabolism, Mitochondrial disorders, Mitochondrial DNA maintenance disorder, Mitochondrial liver disease, Neonatal cholestasis, Possible mitochondrial disorder (nuclear genes), Rhabdomyolysis and metabolic muscle disorders, Undiagnosed metabolic disorders, and White matter disorders and cerebral calcification - childhood onset.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Acute rhabdomyolysis · R419 NHS GMS → Cholestasis · R171 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Mitochondrial DNA maintenance disorder · R352 NHS GMS → Mitochondrial liver disease · R317 NHS GMS → Possible mitochondrial disorder, nuclear genes · R63 NHS GMS → Mitochondrial disorders NHS GMS → Rhabdomyolysis and metabolic muscle disorders NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main role of the DGUOK gene?

The DGUOK gene provides instructions for an enzyme called deoxyguanosine kinase, which is crucial for producing and maintaining the building blocks of mitochondrial DNA. This process is essential for normal energy production within cells.

What happens if there are variants in the DGUOK gene?

Variants in the DGUOK gene can lead to deoxyguanosine kinase deficiency, a condition that impairs mitochondrial function. This can affect organs such as the liver, muscles, and brain, leading to a range of symptoms and conditions.

Is DGUOK deficiency an inherited condition?

Yes, deoxyguanosine kinase deficiency is an inherited disorder. It follows an autosomal recessive pattern of inheritance, meaning an individual must inherit two copies of the altered gene (one from each parent) to develop the condition.

References

  1. Brahimi N, Jambou M, Sarzi E. The first founder DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome. Molecular genetics and metabolism. 2009. PMID: 19394258
  2. Dimmock DP, Zhang Q, Dionisi-Vici C. Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase. Human mutation. 2008. PMID: 18205204
  3. Freisinger P, Fütterer N, Lankes E. Hepatocerebral mitochondrial DNA depletion syndrome caused by deoxyguanosine kinase (DGUOK) mutations. Archives of neurology. 2006. PMID: 16908739
  4. Mancuso M, Ferraris S, Pancrudo J. New DGK gene mutations in the hepatocerebral form of mitochondrial DNA depletion syndrome. Archives of neurology. 2005. PMID: 15883261
  5. Slama A, Giurgea I, Debrey D. Deoxyguanosine kinase mutations and combined deficiencies of the mitochondrial respiratory chain in patients with hepatic involvement. Molecular genetics and metabolism. 2005. PMID: 16263314
  6. Saada-Reisch A. Deoxyribonucleoside kinases in mitochondrial DNA depletion. Nucleosides, nucleotides & nucleic acids. 2004. PMID: 15571232
  7. Wang L, Eriksson S. Mitochondrial deoxyguanosine kinase mutations and mitochondrial DNA depletion syndrome. FEBS letters. 2003. PMID: 14623087
  8. Salviati L, Sacconi S, Mancuso M. Mitochondrial DNA depletion and dGK gene mutations. Annals of neurology. 2002. PMID: 12205643
  9. Mandel H, Szargel R, Labay V. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nature genetics. 2001. PMID: 11687800
  10. Adam MP, Bick S, Mirzaa GM. Deoxyguanosine Kinase Deficiency. 1993. PMID: 20301766
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .