On this page
FUCA1
alpha-L-fucosidase 1
The FUCA1 gene provides instructions for producing alpha-L-fucosidase, an enzyme crucial for breaking down specific sugar molecules within cellular lysosomes. The FUCA1 gene encodes the alpha-L-fucosidase enzyme, which is primarily found in lysosomes, the cell's recycling centres.
FUCA1 is located on the short (p) arm of chromosome 1, at band 1p36.11. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 1 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The FUCA1 gene, also known as alpha-L-fucosidase 1, is essential for normal cellular metabolism, specifically within the lysosomes. It directs the synthesis of the alpha-L-fucosidase enzyme, which is responsible for the breakdown of complex sugar molecules that are attached to fats (glycolipids) and proteins (glycoproteins). This enzymatic activity is fundamental for cellular recycling processes and maintaining overall cellular health.
Disruptions to the function of the FUCA1 gene can have significant health implications, as its product is integral to a metabolic pathway. When the enzyme is deficient or non-functional, an accumulation of undigested molecules can occur, leading to the development of specific inherited conditions.
What the gene does
The primary function of the FUCA1 gene product, alpha-L-fucosidase, is to act as a lysosomal hydrolase. Lysosomes are cellular organelles that contain various enzymes designed to break down waste materials and cellular debris. Within these lysosomes, alpha-L-fucosidase specifically targets glycolipids and glycoproteins.
The enzyme's key role involves cleaving (cutting off) fucose sugar molecules from the ends of these complex oligosaccharide chains. This action is a critical step in the catabolism (breakdown) pathway of these molecules. Without a functional alpha-L-fucosidase enzyme, fucose-containing glycolipids and glycoproteins cannot be properly degraded and recycled. Instead, they accumulate within the lysosomes, leading to cellular dysfunction and ultimately manifesting as a lysosomal storage disorder.
Video: Genetics 101
Chromosome location
The FUCA1 gene is located on chromosome 1, specifically at the band position 1p36.11. Chromosome 1 is one of the largest human chromosomes, and the 'p' arm refers to the shorter arm of the chromosome. This precise genomic address helps in mapping and understanding the gene's position within the human genome.
Protein structure
The FUCA1 gene encodes a protein composed of 466 amino acids, known as alpha-L-fucosidase 1. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the FUCA1 gene can influence the production or function of the alpha-L-fucosidase enzyme. These genetic changes can range from single-nucleotide alterations to larger deletions or insertions within the gene sequence. The consequence of such variants is often a reduction or complete loss of the enzyme's activity, leading to impaired breakdown of specific fucose-containing molecules.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1057G>T | p.Glu353Ter | Pathogenic | ★★☆☆ | Fucosidosis |
c.1285_1286insT | p.Asp429fs | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
c.1289_1301del | p.Leu430fs | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
c.194G>A | p.Gly65Asp | Pathogenic | ★★☆☆ | Fucosidosis |
c.551C>G | p.Ser184Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
c.662_662+8del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
c.698G>A | p.Trp233Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
c.699G>A | p.Trp233Ter | Pathogenic | ★★☆☆ | Fucosidosis |
c.768+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
c.7del | p.Ala3fs | Pathogenic/Likely pathogenic | ★★☆☆ | Fucosidosis |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the FUCA1 gene are primarily associated with Fucosidosis. This is a rare, inherited lysosomal storage disorder characterised by a deficiency of the alpha-L-fucosidase enzyme. The resulting accumulation of fucose-containing compounds within cells leads to a range of severe symptoms affecting multiple organ systems.
UK clinical status
The FUCA1 gene is recognised within the NHS Genomic Medicine Service, indicating its clinical relevance in the UK. It is included on several green-rated panels in NHS England's National Genomic Test Directory, meaning there is strong evidence for its association with certain conditions and it is routinely tested. These panels include 'DDG2P', 'Dystonia, chorea or related movement disorder, childhood onset (R57)', 'Early onset or syndromic epilepsy', 'Inherited white matter disorders', 'Intellectual disability', 'Likely inborn error of metabolism (R98)', 'Lysosomal storage disorder (R276)', 'Skeletal dysplasia (R104)', 'Undiagnosed metabolic disorders', and 'White matter disorders and cerebral calcification - childhood onset'.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the FUCA1 gene?
The FUCA1 gene provides instructions for making the alpha-L-fucosidase enzyme, which is crucial for breaking down fucose sugar molecules from complex fats and proteins within cellular lysosomes.
What happens if the FUCA1 gene doesn't work correctly?
If the FUCA1 gene doesn't function correctly, it can lead to a deficiency of the alpha-L-fucosidase enzyme. This causes an accumulation of fucose-containing molecules in lysosomes, resulting in the lysosomal storage disorder known as Fucosidosis.
Is FUCA1 testing available in the UK?
Yes, the FUCA1 gene is included in several green-rated NHS England National Genomic Test Directory panels, indicating it is routinely tested for conditions like lysosomal storage disorders and early-onset neurological disorders.
References
- Willems PJ, Seo HC, Coucke P. Spectrum of mutations in fucosidosis. European journal of human genetics : EJHG. 1999. PMID: 10094192
- Cragg H, Williamson M, Young E. Fucosidosis: genetic and biochemical analysis of eight cases. Journal of medical genetics. 1997. PMID: 9039984
- Willems PJ, Gatti R, Darby JK. Fucosidosis revisited: a review of 77 patients. American journal of medical genetics. 1991. PMID: 2012122