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ALDH3A2
aldehyde dehydrogenase 3 family member A2
The ALDH3A2 gene provides instructions for an enzyme involved in breaking down fatty aldehydes, playing a crucial role in lipid metabolism and cellular energy production. ALDH3A2 encodes fatty aldehyde dehydrogenase, an enzyme essential for converting fatty aldehydes into fatty acids.
ALDH3A2 is located on the short (p) arm of chromosome 17, at band 17p11.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The ALDH3A2 gene belongs to the aldehyde dehydrogenase (ALDH) gene family, which encompasses genes providing instructions for enzymes that modify aldehyde molecules. Specifically, ALDH3A2 is responsible for producing an enzyme critical for breaking down fatty aldehydes into fatty acids, a key step in fatty acid oxidation. This process is fundamental for converting fats into usable energy within the body.
Disruptions in ALDH3A2 function can lead to the accumulation of fatty aldehydes, impacting various tissues and contributing to conditions such as Sjögren-Larsson syndrome.
What the gene does
The ALDH3A2 gene produces an enzyme known as fatty aldehyde dehydrogenase (FALDH). This enzyme plays a vital role in lipid metabolism by catalysing the oxidation of fatty aldehydes to fatty acids. This reaction is a critical component of the fatty acid oxidation pathway, a multi-step process through which fats are broken down to produce energy.
The ALDH3A2 enzyme is expressed in most body tissues, with its highest activity observed in the liver. Within cells, the majority of the ALDH3A2 enzyme is located in the endoplasmic reticulum, an organelle involved in protein processing and transport. The proper functioning of this enzyme is essential for preventing the build-up of potentially toxic fatty aldehyde molecules, which can lead to cellular dysfunction.
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Chromosome location
The ALDH3A2 gene is located on the short (p) arm of chromosome 17 at position 11.2, a region denoted as 17p11.2. This specific genomic location houses the genetic instructions for the fatty aldehyde dehydrogenase enzyme.
Protein structure
The ALDH3A2 gene encodes a protein composed of 485 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the ALDH3A2 gene can affect the production or function of the fatty aldehyde dehydrogenase enzyme. These genetic changes can impair the enzyme's ability to metabolise fatty aldehydes, leading to their accumulation within cells and tissues. Such pathogenic variants are associated with specific inherited conditions.
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.1137del | p.Ser380fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.1198G>A | p.Gly400Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.1268G>A | p.Arg423His | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.1285del | p.Ser429fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.1320T>A | p.Tyr440Ter | Pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.171C>G | p.Tyr57Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.292C>T | p.Gln98Ter | Pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.551C>G | p.Thr184Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.653_654del | p.Lys218fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
c.680+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Sjögren-Larsson syndrome |
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 ALDH3A2 gene are primarily associated with Sjögren-Larsson syndrome, an autosomal recessive inherited disorder. This condition typically affects the skin and eyes, as well as the central nervous system, reflecting the widespread role of the ALDH3A2 enzyme in lipid metabolism.
- Sjögren-Larsson syndrome Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic ALDH3A2 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 ALDH3A2 gene is included in several expert-curated panels within the NHS Genomic Medicine Service's PanelApp. This indicates its clinical relevance for genetic testing in the UK for conditions such as Autosomal recessive congenital ichthyosis, Foetal anomalies, Hereditary spastic paraplegia (childhood onset), and Ichthyosis and erythrokeratoderma. It is also listed for Inherited white matter disorders, Intellectual disability, Leukodystrophy (adult onset), Likely inborn error of metabolism, Palmoplantar keratodermas, Retinal disorders, 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 primary function of the ALDH3A2 gene?
The ALDH3A2 gene provides instructions for an enzyme called fatty aldehyde dehydrogenase, which is crucial for breaking down fatty aldehydes into fatty acids. This process is a key part of how the body converts fats into energy.
Which condition is most commonly associated with ALDH3A2 variants?
Variants in the ALDH3A2 gene are most commonly associated with Sjögren-Larsson syndrome. This is an inherited disorder that affects the skin, eyes, and the central nervous system due to impaired lipid metabolism.
How is Sjögren-Larsson syndrome inherited?
Sjögren-Larsson syndrome is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the pathogenic ALDH3A2 gene variant, one from each parent, to develop the condition.
References
- Rizzo WB, S'Aulis D, Jennings MA. Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion. Archives of dermatological research. 2010. PMID: 20049467
- Ashibe B, Motojima K. Fatty aldehyde dehydrogenase is up-regulated by polyunsaturated fatty acid via peroxisome proliferator-activated receptor alpha and suppresses polyunsaturated fatty acid-induced endoplasmic reticulum stress. The FEBS journal. 2009. PMID: 19860831
- Rizzo WB. Sjögren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Molecular genetics and metabolism. 2007. PMID: 16996289