On this page
ALDH3A2
aldehyde dehydrogenase 3 family member A2
The ALDH3A2 gene provides instructions for an enzyme essential in breaking down fatty aldehydes, playing a crucial role in lipid metabolism within the body. ALDH3A2 encodes fatty aldehyde dehydrogenase (FALDH), an enzyme vital for the metabolism of fats.
ALDH3A2 is located on the short (p) arm of chromosome 17, at band 17p11.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 17 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The ALDH3A2 gene, also known as aldehyde dehydrogenase 3 family member A2, is part of a larger family of genes that produce aldehyde dehydrogenase enzymes. These enzymes are involved in modifying various aldehyde molecules throughout the body. Specifically, ALDH3A2 provides the blueprint for an enzyme that converts fatty aldehydes into fatty acids, a key step in the process of fatty acid oxidation where fats are broken down to produce energy.
What the gene does
The enzyme produced from the ALDH3A2 gene, known as fatty aldehyde dehydrogenase (FALDH), plays a critical role in lipid metabolism. Its primary function is to catalyse the oxidation of fatty aldehydes, converting them into their corresponding fatty acids. This conversion is an integral part of the multistep process of fatty acid oxidation, which is vital for energy production within cells. The ALDH3A2 enzyme is found in most bodily tissues, with particularly high activity observed in the liver. Within cells, the majority of this enzyme is located in the endoplasmic reticulum, an organelle involved in protein processing and transport.
Video: Genetics 101
Chromosome location
The ALDH3A2 gene is located on the short (p) arm of chromosome 17 at position 11.2, denoted as 17p11.2. This specific genomic location helps define its position within our genetic blueprint.
Protein structure
The ALDH3A2 gene codes for a protein that is 485 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations, or variants, in the ALDH3A2 gene can affect the enzyme's ability to properly break down fatty aldehydes. These variants can range from single nucleotide changes to larger deletions or insertions within the gene sequence. Such alterations can lead to a non-functional or reduced-function enzyme, disrupting normal lipid metabolism.
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.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 |
c.699dup | p.Tyr234fs | 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. This inherited condition affects multiple body systems, including the skin (ichthyosis), eyes (retinopathy), and the central nervous system (neurological symptoms). The inability of the ALDH3A2 enzyme to metabolise fatty aldehydes leads to their accumulation within cells, contributing to the symptoms of the syndrome.
- 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 UK's National Health Service (NHS) Genomic Medicine Service. These include panels for Autosomal recessive congenital ichthyosis, Ichthyosis and erythrokeratoderma, Hereditary spastic paraplegia, childhood onset, and Inherited white matter disorders, all of which are categorised as 'green' on PanelApp, indicating strong evidence for gene-disease association. It is also listed under panels for Foetal anomalies (R21), Leukodystrophy, adult onset (R62), Likely inborn error of metabolism (R98), Palmoplantar keratodermas (R166), and Retinal disorders (R32), among others.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the ALDH3A2 gene?
The ALDH3A2 gene provides instructions for making an enzyme called fatty aldehyde dehydrogenase (FALDH). This enzyme is crucial for breaking down fatty aldehydes into fatty acids, a process that is part of the body's fat metabolism and energy production.
What condition is associated with ALDH3A2 gene variants?
Variants in the ALDH3A2 gene are known to cause Sjögren-Larsson syndrome. This condition affects several parts of the body, including the skin, eyes, and brain, due to the accumulation of fatty aldehyde molecules in cells.
How does the ALDH3A2 enzyme affect cells?
The ALDH3A2 enzyme helps prevent the buildup of potentially toxic fatty aldehydes by converting them into harmless fatty acids. When the enzyme is not functioning correctly, these fatty aldehydes can accumulate within cells, leading to cellular dysfunction and the symptoms seen in associated conditions.
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