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ALDOB
aldolase, fructose-bisphosphate B
The ALDOB gene provides instructions for producing aldolase B, an enzyme primarily found in the liver that plays a critical role in metabolising fructose, a simple sugar. ALDOB is essential for the body's ability to process fructose, converting it into components that can be used for energy.
ALDOB is located on the long (q) arm of chromosome 9, at band 9q31.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The ALDOB gene encodes the aldolase B enzyme, which is vital for the proper breakdown of fructose within the body. This enzyme is predominantly active in liver cells, but is also present in kidney and intestinal tissues. Its primary role involves converting fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate, which are then used in other metabolic pathways.
What the gene does
The aldolase B enzyme, produced from the ALDOB gene, is one of three aldolase enzymes responsible for breaking down specific molecules within cells. It functions as a tetramer, meaning four identical aldolase B protein units must bind together to form an active enzyme. This enzyme is critical for the second step in fructose metabolism, where it cleaves fructose-1-phosphate into two smaller molecules, glyceraldehyde and dihydroxyacetone phosphate. While its main role is in fructose breakdown, aldolase B also has a minor involvement in glucose metabolism.
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Chromosome location
The ALDOB gene is located on chromosome 9, specifically at position 9q31.1. This precise location indicates its position on the long arm (q) of chromosome 9, within region 3, band 1, sub-band 1.
Protein structure
The ALDOB gene codes for a protein that is 364 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants in the ALDOB gene can alter the function of the aldolase B enzyme. Many identified variants involve single amino acid changes within the protein, which can reduce the enzyme's ability to process fructose effectively. These changes can lead to impaired fructose metabolism and subsequent health implications.
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.1000-1_1006delinsTG | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
c.113-1G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
c.255C>G | p.Tyr85Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.379+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
c.607C>T | p.Gln203Ter | Pathogenic | ★★☆☆ | Hereditary fructosuria |
c.61C>T | p.Gln21Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
c.742C>T | p.Gln248Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
c.761dup | p.Thr255fs | Pathogenic | ★★☆☆ | Hereditary fructosuria |
c.799+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
c.949_950insCAGGGCCCGTGCACTGGCTGCCTGGGGTGGCA | p.Lys317fs | Pathogenic/Likely pathogenic | ★★☆☆ | Hereditary fructosuria |
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
Variants in the ALDOB gene are associated with hereditary fructose intolerance. This condition is inherited in an autosomal recessive manner, meaning an individual must inherit two affected copies of the gene (one from each parent) to develop the condition. It is characterised by adverse reactions to foods containing fructose.
Inheritance pattern
Conditions caused by pathogenic ALDOB 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 ALDOB gene is included in several NHS England Genomic Medicine Service national test directory panels. It is listed as 'green' on PanelApp UK for conditions such as Cholestasis, Glycogen storage disease, Ketotic hypoglycaemia, Likely inborn error of metabolism, Neonatal cholestasis, and Undiagnosed metabolic disorders, indicating that there is strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the ALDOB gene?
The ALDOB gene provides instructions for creating the aldolase B enzyme, which is crucial for breaking down the sugar fructose in the liver, kidneys, and intestines. This process converts fructose into other molecules the body can use for energy.
What is hereditary fructose intolerance?
Hereditary fructose intolerance is an inherited metabolic disorder caused by variants in the ALDOB gene. Individuals with this condition cannot properly metabolise fructose, leading to a build-up of harmful substances when they consume fructose-containing foods or drinks.
How is hereditary fructose intolerance inherited?
Hereditary fructose intolerance follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of a variant ALDOB gene, one from each parent, to be affected by the condition. Carriers of one variant copy typically do not show symptoms.
References
- Malay AD, Allen KN, Tolan DR. Structure of the thermolabile mutant aldolase B, A149P: molecular basis of hereditary fructose intolerance. Journal of molecular biology. 2005. PMID: 15733923
- Santer R, Rischewski J, von Weihe M. The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. Human mutation. 2005. PMID: 15880727
- Esposito G, Vitagliano L, Santamaria R. Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance. FEBS letters. 2002. PMID: 12417303
- Dalby AR, Tolan DR, Littlechild JA. The structure of human liver fructose-1,6-bisphosphate aldolase. Acta crystallographica. Section D, Biological crystallography. 2001. PMID: 11679716