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LIPA
lipase A, lysosomal acid type
The LIPA gene provides instructions for producing lysosomal acid lipase, an enzyme critical for breaking down fats within cellular lysosomes. The LIPA gene encodes an enzyme called lysosomal acid lipase, which is essential for processing fats such as triglycerides and cholesteryl esters inside cells.
LIPA is located on the long (q) arm of chromosome 10, at band 10q23.31. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The LIPA gene, also known as lipase A, lysosomal acid type, is fundamental for cellular lipid metabolism. It directs the synthesis of lysosomal acid lipase, an enzyme located in lysosomes - the cell's recycling centres. This enzyme plays a vital role in digesting fats, preventing their build-up and ensuring proper cell function.
What the gene does
The protein encoded by the LIPA gene, lysosomal acid lipase, acts within lysosomes to break down specific types of fats. Its primary function involves hydrolysing triglycerides and cholesteryl esters. Cholesteryl esters are broken down into cholesterol and fatty acids, while triglycerides are separated into their constituent fatty acids, which can then be used for energy. The resulting lipid components are either utilised by the body or transported to the liver for removal, highlighting the enzyme's importance in maintaining lipid homeostasis.
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Chromosome location
The LIPA gene is situated on the long arm of chromosome 10, specifically at position 10q23.31. This genomic location specifies its precise address within the human genome.
Protein structure
The LIPA protein comprises 399 amino acids. A key structural feature is the AB hydrolase-1 domain, which spans amino acids 80-380. This domain is characteristic of enzymes involved in hydrolysing ester bonds, consistent with the protein's function in breaking down lipids.
Key variants
Variants within the LIPA gene can alter the function of the lysosomal acid lipase enzyme. These genetic changes can range from small alterations to larger deletions, potentially leading to a reduction or complete loss of enzyme activity. The specific impact of a variant often depends on its location and the resulting effect on protein structure and function.
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.1180_1184del | p.Leu394fs | Pathogenic/Likely pathogenic | ★★☆☆ | Wolman disease |
c.131G>A | p.Trp44Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Wolman disease |
c.132G>A | p.Trp44Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Wolman disease |
c.294C>A | p.Asn98Lys | Pathogenic/Likely pathogenic | ★★☆☆ | Wolman disease |
c.652C>T | p.Arg218Ter | Pathogenic | ★★☆☆ | Wolman disease |
c.694G>T | p.Glu232Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Wolman disease |
c.780_781del | p.Cys261fs | Pathogenic | ★★☆☆ | Wolman disease |
c.890dup | p.Ser297fs | Pathogenic/Likely pathogenic | ★★☆☆ | Wolman disease |
c.929G>A | p.Trp310Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Lysosomal acid lipase deficiency |
c.980del | p.Thr327fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lysosomal acid lipase deficiency |
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 LIPA gene are associated with a spectrum of conditions characterised by lipid accumulation, collectively known as lysosomal acid lipase deficiency. These include Wolman disease and CESD (Cholesteryl Ester Storage Disease). Both conditions result from an inability to properly break down fats, leading to their harmful build-up in various tissues and organs throughout the body.
- Wolman disease / CESD Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic LIPA 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
In the UK, the LIPA gene is reviewed across several NHS Genomic Medicine Service clinical panels, indicating its recognised clinical significance. It is part of panels for Cholestasis, Familial hypercholesterolaemia, Foetal anomalies, Foetal hydrops, Likely inborn error of metabolism, Lysosomal acid lipase deficiency, Lysosomal storage disorder, Neonatal cholestasis, and Undiagnosed metabolic disorders, all listed as 'green' indicating their clinical utility.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the function of the LIPA gene?
The LIPA gene provides instructions for making lysosomal acid lipase, an enzyme critical for breaking down fats like triglycerides and cholesteryl esters within cellular lysosomes. This process is essential for lipid metabolism and preventing harmful fat build-up.
What conditions are associated with variants in the LIPA gene?
Variants in the LIPA gene are associated with lysosomal acid lipase deficiency, which includes conditions such as Wolman disease and CESD (Cholesteryl Ester Storage Disease). These conditions involve the accumulation of lipids in tissues due to insufficient enzyme activity.
Where is the LIPA gene located?
The LIPA gene is located on chromosome 10, specifically at position 10q23.31. This specifies its precise chromosomal address within the human genome.
References
- Reiner Ž, Guardamagna O, Nair D. Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction. Atherosclerosis. 2014. PMID: 24792990
- Zhang B, Porto AF. Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. Journal of pediatric gastroenterology and nutrition. 2013. PMID: 23403440
- Scott SA, Liu B, Nazarenko I. Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G>A) in various racial and ethnic groups. Hepatology (Baltimore, Md.). 2013. PMID: 23424026
- Saito S, Ohno K, Suzuki T. Structural bases of Wolman disease and cholesteryl ester storage disease. Molecular genetics and metabolism. 2012. PMID: 22138108