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GALK1
galactokinase 1
The GALK1 gene provides instructions for the enzyme galactokinase 1, which plays a vital role in metabolising galactose, a sugar found in dairy products and other foods. The GALK1 gene is responsible for producing galactokinase 1, an enzyme essential for the initial steps in converting galactose into other molecules the body can utilise.
GALK1 is located on the long (q) arm of chromosome 17, at band 17q25.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The GALK1 gene, also known as galactokinase 1, encodes an enzyme critical for carbohydrate metabolism. This enzyme is involved in the conversion of galactose, a simple sugar, into forms that the body can use for energy or to build essential molecules.
What the gene does
The GALK1 gene carries the genetic blueprint for galactokinase 1, an enzyme vital for breaking down galactose [PMID:31543787]. Galactose is a simple sugar commonly consumed as part of lactose, found in dairy items and some infant formulas. The galactokinase 1 enzyme initiates a metabolic pathway, transforming galactose into other compounds the body can utilise. Specifically, it converts galactose into galactose-1-phosphate. This intermediate can then undergo further reactions to become glucose, which serves as the primary energy source for most cells. Additionally, galactose-1-phosphate can be incorporated into galactose-containing proteins and fats. These modified macromolecules are essential for cellular communication, constructing cellular components, transporting substances, and generating energy within the body [PMID:17007787].
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Chromosome location
The GALK1 gene is located on chromosome 17, specifically at position 17q25.1. This region denotes its precise address within the human genome, providing a reference point for genetic studies and diagnostic purposes.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the GALK1 gene can impact the function of the galactokinase 1 enzyme, leading to altered galactose metabolism. These genetic changes can range from single amino acid substitutions to larger deletions or insertions, and their clinical significance is assessed based on their effect on enzyme activity.
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.1055_1056del | p.Thr352fs | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.1067T>C | p.Leu356Pro | Pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.1105C>T | p.Gln369Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.1A>G | p.Met1Val | Pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.206dup | p.Asp70fs | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.327dup | p.Val110fs | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.3G>T | p.Met1Ile | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.708C>A | p.Tyr236Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.901A>T | p.Arg301Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
c.98C>G | p.Ser33Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of galactokinase |
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 GALK1 gene are primarily associated with galactokinase deficiency, also known as Type II galactosemia. This inherited metabolic disorder affects the body's ability to process galactose. Infants with galactokinase deficiency typically develop cataracts. Over 30 specific genetic alterations in GALK1 have been linked to this form of galactosemia. Affected infants typically experience fewer long-term complications compared to those with classic galactosemia [PMID:17007787].
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic GALK1 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The GALK1 gene is included in several NHS Genomic Medicine Service national test panels. It is listed as 'green' for conditions such as Bilateral congenital or childhood onset cataracts, Foetal anomalies, Likely inborn error of metabolism, Neonatal cholestasis, and Undiagnosed metabolic disorders, indicating that there is strong evidence for its association with these conditions and it is routinely tested.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the GALK1 gene?
The GALK1 gene provides instructions for an enzyme called galactokinase 1. This enzyme is vital for the initial steps of processing galactose, a sugar found in dairy products, converting it into a form the body can use for energy or other metabolic processes.
What condition is associated with GALK1 gene variants?
Variants in the GALK1 gene are associated with galactokinase deficiency, also known as Type II galactosemia. This inherited metabolic disorder primarily causes cataracts in affected infants.
Is galactokinase deficiency a serious condition?
Galactokinase deficiency typically causes cataracts in infancy. Early diagnosis and dietary management can help address this manifestation. This type of galactosemia is generally milder than other forms, with fewer long-term complications observed [PMID:17007787].
References
- Timson DJ. The molecular basis of galactosemia - Past, present and future. Gene. 2016. PMID: 26143117
- Thoden JB, Holden HM. The molecular architecture of human N-acetylgalactosamine kinase. The Journal of biological chemistry. 2005. PMID: 16006554
- Holden HM, Thoden JB, Timson DJ. Galactokinase: structure, function and role in type II galactosemia. Cellular and molecular life sciences : CMLS. 2004. PMID: 15526155
- Timson DJ, Reece RJ. Functional analysis of disease-causing mutations in human galactokinase. European journal of biochemistry. 2003. PMID: 12694189
- Timson DJ, Reece RJ. Sugar recognition by human galactokinase. BMC biochemistry. 2003. PMID: 14596685
- Adam MP, Bick S, Mirzaa GM. Classic Galactosemia and Clinical Variant Galactosemia. 1993. PMID: 20301691