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GALT
galactose-1-phosphate uridylyltransferase
The *GALT* gene provides instructions for an enzyme crucial for the body's metabolism of galactose, a sugar found in dairy products and many foods. The *GALT* gene is responsible for producing the enzyme galactose-1-phosphate uridylyltransferase.
GALT is located on the short (p) arm of chromosome 9, at band 9p13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The *GALT* gene, or galactose-1-phosphate uridylyltransferase, provides the genetic blueprint for an enzyme essential in the metabolic pathway of galactose [HGNC:4135]. Galactose is a simple sugar derived primarily from lactose, which is present in dairy products and various other foods. This enzyme facilitates the conversion of galactose into compounds that the body can utilise for energy or for building complex molecules.
Disruptions in *GALT* gene function can lead to an accumulation of galactose and its metabolites, which can be toxic. Such accumulation is characteristic of classical galactosaemia, a severe inherited metabolic condition.
What the gene does
The *GALT* gene encodes the enzyme galactose-1-phosphate uridylyltransferase, which is instrumental in the processing of galactose [UniProt:P07902]. This enzyme is responsible for a particular reaction within the Leloir pathway, transforming galactose-1-phosphate into glucose-1-phosphate whilst also generating UDP-galactose. Glucose serves as the predominant fuel for cellular energy needs across most tissues.
UDP-galactose represents an activated form of galactose necessary for incorporating this sugar into proteins and lipids. Such galactose-containing biomolecules participate in diverse cellular functions, ranging from signalling cascades to structural assembly, molecular trafficking, and metabolic energy generation. The enzyme's proper activity is therefore fundamental to galactose processing and to supplying cells with critical structural components.
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Chromosome location
The *GALT* gene is located on chromosome 9, specifically at position 9p13.3 [HGNC:4135]. This particular genomic address specifies its precise place within the human genome. The gene spans a region containing the DNA sequences necessary for producing the galactose-1-phosphate uridylyltransferase enzyme.
Protein structure
The galactose-1-phosphate uridylyltransferase protein consists of 379 amino acids [UniProt:P07902]. A key structural feature includes a Disordered region spanning amino acids 1-21. This region typically lacks a fixed three-dimensional structure under physiological conditions, which can allow for flexibility and participation in various molecular interactions.
Key variants
Variants within the *GALT* gene can alter the enzyme's structure and function, potentially reducing or eliminating its activity. Over 300 different pathogenic variants in the *GALT* gene have been documented in individuals with classical galactosaemia. These genetic alterations are associated with substantially diminished or absent enzyme function. Inheritance follows an autosomal recessive pattern, meaning two altered copies are required for disease manifestation.
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.1054G>C | p.Glu352Gln | Pathogenic/Likely pathogenic | ★★☆☆ | Galactosemia |
c.1A>C | p.Met1Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Galactosemia |
c.253-1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Galactosemia |
c.260C>G | p.Pro87Arg | Pathogenic | ★★☆☆ | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase |
c.377+1G>A | - | Pathogenic | ★★☆☆ | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase |
c.382G>A | p.Val128Ile | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase |
c.460T>C | p.Trp154Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase |
c.505C>A | p.Gln169Lys | Pathogenic/Likely pathogenic | ★★☆☆ | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase |
c.792_793insG | p.Pro265fs | Pathogenic/Likely pathogenic | ★★☆☆ | Galactosemia |
c.820+1G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Galactosemia |
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 *GALT* gene are the underlying cause of classical galactosaemia, a severe inherited metabolic disorder. When the enzyme encoded by *GALT* loses function, the body cannot adequately metabolise galactose, resulting in toxic accumulation of galactose-1-phosphate and related compounds. More than 300 pathogenic changes in this gene have been identified in people with the classical form of the condition. Most of these alterations substantially impair or completely abolish the enzyme's catalytic activity, leading to life-threatening manifestations that typically begin shortly after birth.
Inheritance pattern
Conditions caused by pathogenic GALT 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 *GALT* gene is well-recognised within the UK's clinical genomic landscape. It is included on several NHS Genomic Medicine Service national panels, indicating its importance in diagnosing various conditions. These panels include 'Bilateral congenital or childhood onset cataracts', 'Cholestasis', 'Foetal anomalies', 'Intellectual disability', 'Likely inborn error of metabolism', 'Neonatal cholestasis', 'Primary ovarian insufficiency', and 'Undiagnosed metabolic disorders', all categorised as 'green', signifying strong evidence for gene-disease association and clinical utility.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the GALT gene?
The *GALT* gene provides instructions for an enzyme called galactose-1-phosphate uridylyltransferase, which is crucial for breaking down the sugar galactose into other molecules the body can use for energy or to build essential cellular components.
What condition is associated with variants in the GALT gene?
Variants in the *GALT* gene are primarily associated with classical galactosaemia. This is an inherited metabolic disorder where the body cannot properly process galactose, leading to a harmful accumulation of galactose metabolites.
How is classical galactosaemia inherited?
Classical galactosaemia is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the altered *GALT* gene, one from each parent, to develop the condition. Individuals with only one altered copy are carriers but typically do not show symptoms.
References
- Coelho AI, Trabuco M, Ramos R. Functional and structural impact of the most prevalent missense mutations in classic galactosemia. Molecular genetics & genomic medicine. 2014. PMID: 25614870
- McCorvie TJ, Gleason TJ, Fridovich-Keil JL. Misfolding of galactose 1-phosphate uridylyltransferase can result in type I galactosemia. Biochimica et biophysica acta. 2013. PMID: 23583749
- McCorvie TJ, Timson DJ. The structural and molecular biology of type I galactosemia: Enzymology of galactose 1-phosphate uridylyltransferase. IUBMB life. 2011. PMID: 21793161
- McCorvie TJ, Timson DJ. Structural and molecular biology of type I galactosemia: disease-associated mutations. IUBMB life. 2011. PMID: 21960482
- Bosch AM, Ijlst L, Oostheim W. Identification of novel mutations in classical galactosemia. Human mutation. 2005. PMID: 15841485
- Adam MP, Bick S, Mirzaa GM. Classic Galactosemia and Clinical Variant Galactosemia. 1993. PMID: 20301691
- Adam MP, Bick S, Mirzaa GM. Duarte Galactosemia. 1993. PMID: 25473725