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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FCSK
fucose kinase
Chromosome 16 Β· 16q22.1
NCBI Gene: 197258Ensembl: ENSG00000157353.18HGNC: HGNC:29500UniProt: Q8N0W3
22PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
fucokinase activityGDP-L-fucose salvageprotein bindingGDP-L-fucose biosynthetic processcongenital disorder of glycosylation with defective fucosylationcongenital disorder of glycosylationDental malocclusionNeurodevelopmental disorder
✦AI Summary

FCSK encodes fucokinase, an enzyme that catalyzes the phosphorylation of L-fucose to fucose-1-phosphate, serving a critical role in the fucose salvage pathway for glycoprotein fucosylation 12. The enzyme is essential for maintaining proper protein glycosylation, particularly affecting O-fucosylation of proteins like NOTCH3 3. FCSK deficiency causes FCSK-congenital disorder of glycosylation (FCSK-CDG), a rare autosomal recessive disorder characterized by intellectual disability, growth delay, seizures, feeding difficulties, and ophthalmic abnormalities 14. The disease appears to primarily affect secretory glycoproteins rather than cell surface glycans 3. Animal studies using fcsk knockout zebrafish demonstrate neurodevelopmental abnormalities including impaired growth, brain atrophy, locomotor deficits, increased seizure susceptibility, and memory impairment 2. These defects can be rescued by GDP-L-fucose supplementation, confirming the enzyme's role in fucosylation 2. Currently, only a handful of patients with FCSK-CDG have been reported worldwide, with phenotypes ranging from severe developmental delays to milder presentations 5. The rarity of this condition highlights the critical importance of fucose metabolism in human development and neurological function.

Sources cited
1
FCSK deficiency causes autosomal recessive FCSK-CDG with intellectual disability, growth delay, and other symptoms
PMID: 35718084
2
FCSK affects O-fucosylation of NOTCH3 and primarily impacts secretory glycoproteins
PMID: 38722107
3
FCSK catalyzes L-fucose phosphorylation and knockout zebrafish show neurodevelopmental defects rescued by GDP-L-fucose
PMID: 40049660
4
FCSK-CDG can present with mild phenotypes including resolved infantile spasms
PMID: 36426412
5
FCSK-CDG is one of only five known CDG types with defective fucosylation
PMID: 34389986
Disease Associationsβ“˜21
congenital disorder of glycosylation with defective fucosylationOpen Targets
0.69Moderate
congenital disorder of glycosylationOpen Targets
0.37Weak
Dental malocclusionOpen Targets
0.30Weak
Neurodevelopmental disorderOpen Targets
0.15Weak
heart diseaseOpen Targets
0.05Suggestive
osteoarthritis, hipOpen Targets
0.04Suggestive
osteoarthritis, kneeOpen Targets
0.04Suggestive
metabolic diseaseOpen Targets
0.03Suggestive
melanomaOpen Targets
0.03Suggestive
hyperlipidemiaOpen Targets
0.03Suggestive
hypertensionOpen Targets
0.03Suggestive
coronary artery diseaseOpen Targets
0.03Suggestive
myocardial infarctionOpen Targets
0.03Suggestive
angina pectorisOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
AnxietyOpen Targets
0.01Suggestive
metastatic melanomaOpen Targets
0.01Suggestive
Congenital disorder of glycosylation with defective fucosylation 2UniProt
Pathogenic Variants5
NM_145059.3(FCSK):c.1000_1018del (p.Glu335fs)Pathogenic
Congenital disorder of glycosylation with defective fucosylation 2
β˜…β˜…β˜†β˜†2024β†’ Residue 335
NM_145059.3(FCSK):c.3255A>G (p.Ter1085Trp)Likely pathogenic
Congenital disorder of glycosylation with defective fucosylation 2
β˜…β˜†β˜†β˜†2025β†’ Residue 1085
NM_145059.3(FCSK):c.956-1G>ALikely pathogenic
Congenital disorder of glycosylation with defective fucosylation 2
β˜…β˜†β˜†β˜†2024
NM_145059.3(FCSK):c.503_527dup (p.Pro180fs)Likely pathogenic
Congenital disorder of glycosylation with defective fucosylation 2
β˜…β˜†β˜†β˜†2023β†’ Residue 180
NM_145059.3(FCSK):c.412-2A>GLikely pathogenic
Congenital disorder of glycosylation with defective fucosylation 2
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
GNPTGShared pathway100%FPGTProtein interaction95%HK2Protein interaction93%HK3Protein interaction92%GALTProtein interaction82%GALMProtein interaction82%
Tissue Expression6 tissues
Liver
100%
Ovary
92%
Lung
69%
Bone Marrow
50%
Heart
35%
Brain
23%
Gene Interaction Network
Click a node to explore
FCSKGNPTGFPGTHK2HK3GALTGALM
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8N0W3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.25LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.08 [0.93–1.25]
RankingsWhere FCSK stands among ~20K protein-coding genes
  • #13,663of 20,598
    Most Researched22
  • #3,631of 5,498
    Most Pathogenic Variants5
  • #13,229of 17,882
    Most Constrained (LOEUF)1.25
Genes detectedFCSK
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A combination of two novels homozygous FCSK variants cause disorder of glycosylation with defective fucosylation: New patient and literature review.
PMID: 35718084
Eur J Med Genet Β· 2022
1.00
2
Novel insight into FCSK-congenital disorder of glycosylation through a CRISPR-generated cell model.
PMID: 38722107
Mol Genet Genomic Med Β· 2024
0.90
3
Structural and functional analysis of fucose-processing enzymes from Streptococcus pneumoniae.
PMID: 24333485
J Mol Biol Β· 2014
0.80
4
Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.
PMID: 33196155
N Engl J Med Β· 2020
0.70
5
Congenital disorders of glycosylation with defective fucosylation.
PMID: 34389986
J Inherit Metab Dis Β· 2021
0.60