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Mitochondrial disorders

Gene: GUK1

Amber List (moderate evidence)

GUK1 (guanylate kinase 1)
EnsemblGeneIds (GRCh38): ENSG00000143774
EnsemblGeneIds (GRCh37): ENSG00000143774
OMIM: 139270, Gene2Phenotype
GUK1 is in 4 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Comment on phenotypes: OMIM phenotype last accessed on 28 October 2025.
Created: 28 Oct 2025, 3:15 p.m. | Last Modified: 28 Oct 2025, 3:15 p.m.
Panel Version: 9.36

Arina Puzriakova (Genomics England Curator)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - 4 individuals from 3 unrelated families with biallelic variants leading to GUK1 deficiency. Muscle biopsies showed mtDNA depletion and/or deletions and reduced activities of mitochondrial respiratory chain enzymes.
Created: 29 Aug 2025, 4:03 p.m. | Last Modified: 29 Aug 2025, 4:03 p.m.
Panel Version: 9.26

Hannah Knight (NIHR BioResource - University of Cambridge)

Green List (high evidence)

Four patients from three families reported with mitochondrial disorders and biallelic GUK1 variants. Different variants in all three families.
Key symptoms include ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy
Sources: Literature
Created: 22 Jul 2025, 9:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 21

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Mitochondrial DNA depletion syndrome 21, OMIM:621071
  • mitochondrial dna depletion syndrome 21, MONDO:0976132
Tags
Q3_25_promote_green Q3_25_NHS_review
OMIM
139270
Clinvar variants
Variants in GUK1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Oct 2025, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: GUK1 were changed from Mitochondrial DNA depletion syndrome 21, OMIM:621071 to Mitochondrial DNA depletion syndrome 21, OMIM:621071; mitochondrial dna depletion syndrome 21, MONDO:0976132

29 Aug 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: guk1 has been classified as Amber List (Moderate Evidence).

29 Aug 2025, Gel status: 0

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: GUK1. Tag Q3_25_NHS_review tag was added to gene: GUK1.

29 Aug 2025, Gel status: 0

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: GUK1 were set to PMID: 39230499

29 Aug 2025, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: GUK1 were changed from Mitochondrial DNA depletion syndrome 21 to Mitochondrial DNA depletion syndrome 21, OMIM:621071

22 Jul 2025, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Hannah Knight (NIHR BioResource - University of Cambridge)

gene: GUK1 was added gene: GUK1 was added to Mitochondrial disorders. Sources: Literature Mode of inheritance for gene: GUK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GUK1 were set to PMID: 39230499 Phenotypes for gene: GUK1 were set to Mitochondrial DNA depletion syndrome 21 Review for gene: GUK1 was set to GREEN