GUK1

protein-coding

guanylate kinase 1

Gene summary

The protein encoded by this gene is an enzyme that catalyzes the transfer of a phosphate group from ATP to guanosine monophosphate (GMP) to form guanosine diphosphate (GDP). The encoded protein is thought to be a good target for cancer chemotherapy. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

MANE transcript

NM_001159390.2

Inheritance

ClinVar variants

P:4U:47B:1

Top phenotype

Mitochondrial DNA depletion syndrome 21

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr1:228,139,962-228,148,984

External References & Databases

Ensembl (ENSG00000143774)

Transcript & Mutation Effects

hg38 • Region Span ~9.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: Ambry Genetics

mitochondrial DNA depletion syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018158

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Mitochondrial DNA depletion syndrome 21AR

Manifestation: Allergy/Immunology/Infectious; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Refs: 39230499

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GUK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

Mitochondrial dna depletion syndrome 21Total: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001159390.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	1 clinvar		5
missense	1 clinvar		37 clinvar			38
nonsense	1 clinvar					1
start loss	1 clinvar					1
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	3	1	47	1	0	52

Highest pathogenic variant AF is 0.00010119143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 151 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001159390.2	RefSeq	NP_001152862.1	8	MANE Select
ENST00000453943.6	Ensembl	ENSP00000401832.2	8	MANE Select
NM_000858.7	RefSeq	NP_000849.1	7	Standard
NM_001159391.3	RefSeq	NP_001152863.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Abacavir Pathway, Pharmacokinetics/Pharmacodynamics
Purine Nucleoside Phosphorylase Deficiency
Mercaptopurine Action Pathway
Azathioprine Action Pathway

Biological Process

purine nucleotide metabolic process
dGDP biosynthetic process
nucleobase-containing small molecule interconversion
GDP-mannose metabolic process
glycoprotein transport

Molecular Function

guanylate kinase activity
ATP binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366728
Coding exons: 7
Length: 9023
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125701
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0812	161	164	0.982	0.0000112	1540
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.00036	0.00036	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for recycling GMP and indirectly, cGMP.;

Recessive Scores

pRec: 0.398

Intolerance Scores

LoFtool: 0.871
RVIS EVS: -0.96
RVIS percentile EVS: 9.09

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.551

Gene Damage Prediction

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