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ALDOB
aldolase, fructose-bisphosphate B
The ALDOB gene provides instructions for producing aldolase B, an enzyme primarily active in the liver and essential for processing dietary fructose. The ALDOB gene is responsible for creating the aldolase B enzyme, which plays a vital role in metabolising fructose, a simple sugar found in fruits.
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, a key player in carbohydrate metabolism, particularly the breakdown of fructose. This enzyme is predominantly found in the liver, but also in the kidneys and intestinal cells. Its proper function is critical for preventing the accumulation of toxic by-products from fructose consumption [PMID:20301416].
Individuals with alterations in the ALDOB gene may experience hereditary fructose intolerance, a condition characterised by adverse reactions to fructose. Understanding the ALDOB gene and its functions is important for carrier screening and diagnosing this inherited metabolic disorder.
What the gene does
The aldolase B enzyme, produced from the ALDOB gene, is one of three aldolase enzymes involved in breaking down specific molecules within cells. For the enzyme to be active, four identical aldolase B units must assemble into a functional tetramer. Its main role is in the metabolism of fructose, a simple sugar used by the body for energy [PMID:20301416].
Specifically, aldolase B catalyses the second step in fructose metabolism, converting fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate. While its primary role is in fructose breakdown, it also participates to a lesser extent in glucose metabolism. Impaired function of aldolase B can lead to difficulties in processing fructose, resulting in health complications [PMID:20301416].
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Chromosome location
The ALDOB gene is located on chromosome 9, specifically at position 9q31.1. This genomic address specifies its precise place within the human genome, aiding in its identification and study.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the ALDOB gene can affect the function of the aldolase B enzyme. Many identified variants involve single amino acid changes that can reduce the enzyme's activity or stability. Over 50 different types of variants have been associated with impaired aldolase B function [PMID:19420330].
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.136del | p.Arg46fs | 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 |
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 primarily associated with hereditary fructose intolerance. This is an autosomal recessive condition, meaning an individual must inherit two affected copies of the gene (one from each parent) to develop the condition. Symptoms typically arise after consuming foods containing fructose, leading to nausea and intestinal discomfort.
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 part of several NHS England's National Genomic Test Directory panels, indicating its clinical significance within the UK. It is included in panels for Cholestasis, Glycogen storage disease, Ketotic hypoglycaemia, Likely inborn error of metabolism, Neonatal cholestasis, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the ALDOB gene?
The ALDOB gene provides instructions for the aldolase B enzyme, which is crucial for breaking down fructose, a simple sugar, particularly in the liver. It converts fructose-1-phosphate into other molecules for energy use.
What condition is associated with ALDOB gene variants?
Variants in the ALDOB gene are primarily associated with hereditary fructose intolerance. This condition leads to adverse reactions, such as nausea and intestinal discomfort, after consuming foods that contain fructose.
How is hereditary fructose intolerance inherited?
Hereditary fructose intolerance is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered ALDOB gene, one from each parent, to develop the condition.
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