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

mitochondrial disease (Limited), mode of inheritance: AR

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.

not_specified (34 variants)
Mitochondrial_dna_depletion_syndrome_21 (4 variants)

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. These statistics are base on transcript: NM_001159390.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense	1 clinvar		33 clinvar			34
nonsense	1 clinvar					1
start loss	1					1
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	4	0	34	0	0

Highest pathogenic variant AF is 0.000101191

Loading clinvar variants...

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 de novo biosynthesis;guanosine ribonucleotides de novo biosynthesis;purine nucleotides de novo 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
Phenotype

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