DGUOK

deoxyguanosine kinase, the group of Deoxyribonucleoside kinases

Basic information

Region (hg38): 2:73926825-73958961

Links

ENSG00000114956 ∙ NCBI:1716 ∙ OMIM:601465 ∙ HGNC:2858 ∙ Uniprot:Q16854 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (Definitive), mode of inheritance: AR
• portal hypertension, noncirrhotic (Limited), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (Supportive), mode of inheritance: AR
• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (Supportive), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)	AR	Gastrointestinal	In individuals with isolated liver disease, liver transplantation has been described as potentially beneficial, though there has been no reported survival advantage in instances of multisystem illness; Awareness may allow prompt recognition and treatment of manifestations such as neonatal hypoglycemia and hepatic dysfunction	Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	11687800; 12205643; 15883261; 15887277; 16908739; 18205204; 18825706; 20301766; 21534344; 22137549; 22602837; 22622127; 22868686; 23043144; 23141463; 26874653

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DGUOK gene.

• not provided (209 variants)
• Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (47 variants)
• not specified (24 variants)
• Inborn genetic diseases (14 variants)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (10 variants)
• Mitochondrial DNA depletion syndrome (6 variants)
• DGUOK-Related Disorders (3 variants)
• 7 conditions (2 variants)
• Portal hypertension, noncirrhotic (2 variants)
• Mitochondrial DNA depletion syndrome 3 (hepatocerebral type);Portal hypertension, noncirrhotic, 1;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (1 variants)
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4;Portal hypertension, noncirrhotic, 1;Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (1 variants)
• See cases (1 variants)
• Portal hypertension, noncirrhotic, 1 (1 variants)
• DGUOK-related condition (1 variants)
• Mitochondrial DNA depletion syndrome 3 (hepatocerebral type);Portal hypertension, noncirrhotic;Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DGUOK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	28	1	32
missense	3	5	79	4		91
nonsense	8		1			9
start loss	3					3
frameshift	11					11
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	4	1			6
splice region	3	1	4	8		16
non coding		1	9	27	12	49
Total	26	10	94	59	13

Highest pathogenic variant AF is 0.0000460

Variants in DGUOK

This is a list of pathogenic ClinVar variants found in the DGUOK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-73926849-C-CAGCG		Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
2-73926857-C-A		Mitochondrial DNA depletion syndrome	Uncertain significance (Jun 14, 2016)
2-73926861-GGGCGGAAGTGCTCTC-G			Benign (Mar 03, 2015)
2-73926863-G-A		not specified • Mitochondrial DNA depletion syndrome	Benign/Likely benign (Jun 14, 2016)
2-73926890-G-T		Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)	Uncertain significance (Jan 12, 2018)
2-73926901-C-T		DGUOK-related disorder	Likely benign (Mar 23, 2020)
2-73926903-T-C		Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) • DGUOK-related disorder	Conflicting classifications of pathogenicity (Aug 09, 2021)
2-73926906-G-A		DGUOK-related disorder	Likely benign (Feb 21, 2023)
2-73926909-G-T		DGUOK-related disorder	Likely benign (Aug 22, 2023)
2-73926910-G-A		Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)	Conflicting classifications of pathogenicity (Jan 19, 2021)
2-73926911-A-G			Pathogenic (Jun 03, 2022)
2-73926912-T-C			Pathogenic (Oct 14, 2023)
2-73926913-G-A			Pathogenic (Aug 16, 2023)
2-73926914-G-T		Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) • DGUOK-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2024)
2-73926916-C-G			Likely benign (Jul 25, 2023)
2-73926916-C-T			Likely benign (Aug 23, 2023)
2-73926917-G-C			Uncertain significance (May 15, 2019)
2-73926917-G-T			Uncertain significance (Sep 29, 2022)
2-73926918-C-A			Uncertain significance (Jul 20, 2022)
2-73926918-C-G		not specified	Conflicting classifications of pathogenicity (Jul 26, 2022)
2-73926919-G-C			Likely benign (Oct 26, 2023)
2-73926919-G-T		Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)	Conflicting classifications of pathogenicity (Nov 28, 2022)
2-73926923-C-T		Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) • Inborn genetic diseases	Uncertain significance (Mar 16, 2022)
2-73926924-G-A		Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4	Uncertain significance (May 31, 2022)
2-73926925-C-T			Likely benign (Nov 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DGUOK	protein_coding	protein_coding	ENST00000264093	7	32136

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.71e-7	0.584	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.468	165	149	1.11	0.00000765	1814
Missense in Polyphen		51	50.984	1.0003		640
Synonymous	-0.503	63	58.1	1.08	0.00000292	530
Loss of Function	0.989	12	16.3	0.736	8.12e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphorylates deoxyguanosine and deoxyadenosine in the mitochondrial matrix, with the highest efficiency for deoxyguanosine. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on DGUOK and TK2. Phosphorylates certain nucleoside analogs. Widely used as target of antiviral and chemotherapeutic agents. {ECO:0000269|PubMed:11687801, ECO:0000269|PubMed:17073823, ECO:0000269|PubMed:23043144, ECO:0000269|PubMed:8706825}.
• Disease: DISEASE: Portal hypertension, non-cirrhotic (NCPH) [MIM:617068]: An autosomal recessive disorder characterized by portal hypertension associated with hepatosplenomegaly, in absence of cirrhosis, extrahepatic diseases, and splanchnic venous thrombosis. Portal hypertension is defined by a portal venous system pressure that is at least 5 mm Hg higher than the pressure in the inferior vena cava. High pressure in the portal venous system leads to shunting of blood through vessels that are poorly suited to carrying large blood volumes, resulting in collateral circulation and splenomegaly. NCPH patients show normal liver function. {ECO:0000269|PubMed:17073823, ECO:0000269|PubMed:26874653}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (PEOB4) [MIM:617070]: A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB4 patients manifest clinically variable features including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis, and adult-onset lower motor neuron syndrome with mild cognitive impairment. {ECO:0000269|PubMed:23043144}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Purine metabolism;Metabolism of nucleotides;purine deoxyribonucleosides salvage;Purine metabolism;Metabolism;Nucleotide salvage;Purine salvage (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.208
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.0688
• hipred: N
• hipred_score: 0.477
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.784

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dguok

Gene ontology

• Biological process: protein phosphorylation;guanosine metabolic process;deoxyribonucleoside monophosphate biosynthetic process;nucleotide biosynthetic process;negative regulation of neuron projection development;purine-containing compound salvage;dGTP metabolic process;purine deoxyribonucleoside metabolic process
• Cellular component: nucleus;cytoplasm;mitochondrion;mitochondrial matrix;cytosol
• Molecular function: deoxyguanosine kinase activity;ATP binding;deoxynucleoside kinase activity;nucleoside kinase activity