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Intellectual disability

Gene: FUK

Amber List (moderate evidence)

FUK (fucokinase)
EnsemblGeneIds (GRCh38): ENSG00000157353
EnsemblGeneIds (GRCh37): ENSG00000157353
OMIM: 608675, Gene2Phenotype
FUK is in 3 panels

3 reviews

Catherine Snow (Genomics England)

Comment on list classification: FCSK/FUK was added to the ID panel and rated Amber by Konstantinos Varvagiannis. Ng et al. (PMID: 30503518) report on 2 unrelated individuals with biallelic pathogenic variants in FUK. This has been added to OMIM and DDG2P. As there are no further cases or animal models to support these variants in the literature, inline with current guidelines, gene will remain Amber.
Created: 21 May 2019, 9:22 a.m.

Louise Daugherty (Genomics England Curator)

Added new-gene-name tag, new approved HGNC gene symbol for FUK is FCSK
Created: 1 Mar 2019, 4:11 p.m.

Konstantinos Varvagiannis (Other)

I don't know

Ng et al. (PMID: 30503518) report on 2 unrelated individuals with biallelic pathogenic variants in FUK. The common features consisted of feeding difficulties, hypotonia, global developmental delay with severe intellectual disability, seizures as well as visual impairment.

The first patient was compound heterozygous for 2 missense variants (Ser223Pro and Arg683Cys) while the second - born to consanguineous parents - was homozygous for Lys994Gln.

Significant reduction in the FUK protein amount was demonstrated upon Western blot for the first individual for whom fibroblast and lymphoblast cell lines were available.

Fucokinase (FUK) is an enzyme of the fucose salvage pathway, one of the mechanisms (the other and main contributor being the de novo pathway) for synthesis of GDP-fucose. GDP-fucose is a donor substrate for fucosylation, a form of glycosylation. Significant decrease of fucokinase activity was shown for this individual when compared to controls.

Cell lines from the second individual were not available for expression/functional studies.

Overall the authors suggest that loss-of-function variants cause a congenital disorder of glycosylation with ID and seizures.

There are no further cases published in the literature.

FUK is not associated with any phenotype in OMIM nor in G2P.

As a result this gene can be considered for inclusion in this panel as amber.

[You might consider inclusion of this gene also in the CDG gene panel].
Sources: Literature
Created: 13 Dec 2018, 7:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Feeding difficulties; Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert Review
  • Expert Review
Phenotypes
  • Seizures
  • Generalized hypotonia
  • Feeding difficulties
  • Intellectual disability
  • Global developmental delay
  • Congenital disorder of glycosylation with defective fucosylation 2, 618324
Tags
watchlist new-gene-name
OMIM
608675
Clinvar variants
Variants in FUK
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Added Tag

Catherine Snow (Genomics England)

Tag watchlist tag was added to gene: FUK.

25 Jul 2019, Gel status: 2

Added New Source, Added New Source, Set Phenotypes, Status Update

Catherine Snow (Genomics England)

Source Expert Review was added to FUK. Source Expert Review Amber was added to FUK. Added phenotypes Congenital disorder of glycosylation with defective fucosylation 2, 618324 for gene: FUK Rating Changed from No List (delete) to Amber List (moderate evidence)

1 Mar 2019, Gel status: 0

Added Tag

Louise Daugherty (Genomics England Curator)

Tag new-gene-name tag was added to gene: FUK.

13 Dec 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: FUK was added gene: FUK was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FUK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUK were set to 30503518 Phenotypes for gene: FUK were set to Feeding difficulties; Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures Penetrance for gene: FUK were set to Complete Review for gene: FUK was set to AMBER