Likely inborn error of metabolism

Gene: GUK1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of this gene with mitochondrial DNA depletion syndrome 21. As this gene has already been recommended for promotion to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/GUK1/) this gene should also be considered for green rating on this panel in the next GMS update.

Created: 28 Oct 2025, 3:18 p.m. | Last Modified: 28 Oct 2025, 3:18 p.m.

Panel Version: 8.78

Comment on phenotypes: OMIM phenotype accessed on 28 October 2025.

Created: 28 Oct 2025, 3:14 p.m. | Last Modified: 28 Oct 2025, 3:14 p.m.

Panel Version: 8.77

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 21, OMIM:621071; mitochondrial dna depletion syndrome 21, MONDO:0976132

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

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

• PMID: 39230499