GUK1

guanylate kinase 1

Basic information

Region (hg38): 1:228139962-228148984

Links

ENSG00000143774 ∙ NCBI:2987 ∙ OMIM:139270 ∙ HGNC:4693 ∙ Uniprot:Q16774 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 21	AR	Allergy/Immunology/Infectious	Among other features, the condition has been reported as involving T-cell dysfunction and frequent infections, and awareness may allow early and aggressive treatment of infections	Allergy/Immunology/Infectious; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	39230499

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GUK1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUK1 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			1			1
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	2		4
Total	0	0	26	2	0

Variants in GUK1

This is a list of pathogenic ClinVar variants found in the GUK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-228140304-T-G		Mitochondrial dna depletion syndrome 21	Pathogenic (Jan 23, 2025)
1-228140322-C-G		not specified	Uncertain significance (Mar 07, 2024)
1-228140325-G-T		not specified	Uncertain significance (Mar 06, 2023)
1-228140339-G-T		not specified	Uncertain significance (Nov 25, 2024)
1-228140355-C-T		not specified	Uncertain significance (Jul 26, 2022)
1-228140364-G-T		Mitochondrial dna depletion syndrome 21	Pathogenic (Jan 23, 2025)
1-228145543-G-A		Mitochondrial dna depletion syndrome 21	Pathogenic (Jan 23, 2025)
1-228145588-C-T		Mitochondrial dna depletion syndrome 21	Pathogenic (Jan 23, 2025)
1-228146041-C-T		not specified	Uncertain significance (Dec 25, 2024)
1-228146049-G-C		not specified	Uncertain significance (Feb 27, 2023)
1-228146901-G-A		not specified	Uncertain significance (May 28, 2024)
1-228146924-C-A		not specified	Uncertain significance (Nov 27, 2023)
1-228147440-C-G		not specified	Uncertain significance (Sep 05, 2024)
1-228147441-G-A		not specified	Uncertain significance (Nov 07, 2022)
1-228147449-G-A		not specified	Uncertain significance (Jan 31, 2022)
1-228147458-G-A		not specified	Uncertain significance (Jun 18, 2021)
1-228147471-G-T		not specified	Uncertain significance (Mar 03, 2025)
1-228147473-G-A		not specified	Uncertain significance (Sep 17, 2021)
1-228147487-G-C		not specified	Uncertain significance (Nov 25, 2024)
1-228147495-A-T		not specified	Uncertain significance (Aug 13, 2021)
1-228147501-G-A		not specified	Uncertain significance (Aug 26, 2024)
1-228147621-C-T		not specified	Uncertain significance (Feb 13, 2025)
1-228147622-G-A		not specified	Uncertain significance (Jun 30, 2022)
1-228147660-G-T		not specified	Uncertain significance (Sep 13, 2022)
1-228147667-G-A		not specified	Uncertain significance (Jul 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GUK1	protein_coding	protein_coding	ENST00000366728	7	9023

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000233	0.517	125676	0	25	125701	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0812	161	164	0.982	0.0000112	1540
Missense in Polyphen		65	68.825	0.94442		575
Synonymous	1.02	59	69.8	0.845	0.00000491	507
Loss of Function	0.604	8	10.1	0.795	5.24e-7	108

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000552	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000892	0.0000880
Middle Eastern	0.0000552	0.0000544
South Asian	0.000361	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for recycling GMP and indirectly, cGMP.
• Pathway: Purine metabolism - Homo sapiens (human);Abacavir Pathway, Pharmacokinetics/Pharmacodynamics;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;Metabolism of nucleotides;purine deoxyribonucleosides salvage;Interconversion of nucleotide di- and triphosphates;Abacavir metabolism;Abacavir transport and metabolism;Metabolism;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;guanosine nucleotides <i>de novo</i> biosynthesis;guanosine ribonucleotides <i>de novo</i> biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.398

Intolerance Scores

• loftool: 0.871
• rvis_EVS: -0.96
• rvis_percentile_EVS: 9.09

Haploinsufficiency Scores

• pHI: 0.619
• hipred: N
• hipred_score: 0.144
• ghis: 0.507

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.551

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Guk1

Gene ontology

• Biological process: purine nucleotide metabolic process;dGDP biosynthetic process;nucleobase-containing small molecule interconversion;GDP-mannose metabolic process;glycoprotein transport;ATP metabolic process;GMP metabolic process;dGMP metabolic process;dATP metabolic process;GDP biosynthetic process;nucleotide phosphorylation
• Cellular component: cytosol
• Molecular function: guanylate kinase activity;ATP binding