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LIPN
lipase family member N
LIPN is located on the long (q) arm of chromosome 10, at band 10q23.31. Arm ratio per GRCh38 - banding schematic.
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Overview
LIPN is located on chromosome 10 and belongs to a family of enzymes called lipases, which typically break down fats and other lipid molecules. While many lipases function in digestion or energy metabolism, LIPN appears to have a specialised role in the skin, particularly in the outermost protective layer known as the epidermis.
Variants in LIPN are inherited in an autosomal recessive pattern, meaning that an individual must inherit two altered copies of the gene - one from each parent - for a related condition to develop. Carriers of a single pathogenic variant typically remain unaffected. Research into LIPN has illuminated how precise lipid processing contributes to the structural integrity of the skin barrier, a complex arrangement of cells and fats that prevents water loss and protects against environmental damage.
What the gene does
Lipase family member N is thought to participate in the processing or modification of lipids within the epidermis, the skin's outermost cellular layer. The epidermis relies on a carefully organised mixture of lipids - including ceramides, cholesterol, and free fatty acids - to form an effective barrier. Disruption of lipid composition or arrangement can compromise barrier function, leading to increased water loss and susceptibility to irritation.
While the precise enzymatic activity of LIPN has not been fully characterised, the protein's structure suggests it may act on specific lipid substrates critical for maintaining the skin's protective properties. Research indicates that proper lipid metabolism in the epidermis is essential for keratinocyte differentiation, the process by which skin cells mature and form the tough, protective outer layers of the palms and soles. Loss of LIPN function is thought to interfere with this differentiation process, resulting in abnormal thickening of the skin in these areas.
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Chromosome location
LIPN is located at chromosomal position 10q23.31, on the long arm of chromosome 10. This region contains numerous genes, some of which also contribute to skin function and immune responses. The precise genomic structure of LIPN, including the number and organisation of exons, has been mapped through sequencing studies, though detailed transcriptional regulation remains an area of ongoing investigation.
Protein structure
The LIPN protein comprises 398 amino acids and contains an AB hydrolase-1 domain spanning amino acids 79 to 379. This domain is characteristic of the alpha-beta hydrolase superfamily, a diverse group of enzymes that share a common structural fold and typically catalyse the cleavage of ester or amide bonds. The AB hydrolase-1 domain likely confers the enzymatic activity of LIPN, enabling it to interact with and modify lipid substrates within the skin.
Key variants
Pathogenic variants in LIPN disrupt the protein's ability to process lipids properly in the skin. These alterations may include missense changes that impair enzymatic activity, frameshift or nonsense variants that truncate the protein, or changes affecting the AB hydrolase domain's catalytic machinery. The variant landscape for LIPN is still being characterised as more families with palmoplantar keratoderma undergo genetic testing.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Variants in LIPN are associated with palmoplantar keratoderma, a group of inherited conditions characterised by abnormal thickening of the skin on the palms of the hands and soles of the feet. Individuals with biallelic LIPN variants may develop diffuse or focal areas of hyperkeratosis, which can cause discomfort, difficulty walking, and increased risk of fissuring or secondary infection. The severity and distribution of skin thickening can vary between affected individuals, even within the same family, suggesting that additional genetic or environmental factors may influence the clinical presentation.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic LIPN 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
LIPN is included in NHS Genomic Medicine Service gene panels for dermatological conditions. It appears on the Developmental Disorders Genotype-to-Phenotype (DDG2P) database with a green classification, indicating strong evidence linking the gene to developmental skin abnormalities. LIPN is also listed on the Palmoplantar Keratodermas panel (R166) with green status, reflecting its established role in these inherited skin conditions. Inclusion on these panels means that LIPN variants may be reported when identified during NHS genomic testing for individuals with relevant clinical features.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is LIPN inherited?
LIPN-related conditions follow an autosomal recessive inheritance pattern. This means an individual must inherit a pathogenic variant from both parents to be affected. Carriers with one altered copy typically have no symptoms.
What does the LIPN protein do in the skin?
LIPN is thought to process lipids within the epidermis, contributing to the formation of the skin's protective barrier. Proper lipid organisation is essential for preventing water loss and maintaining the structural integrity of the skin, particularly on the palms and soles.
Can LIPN variants affect areas other than the palms and soles?
Current evidence suggests that LIPN variants primarily affect the palms and soles, where the skin is naturally thicker and relies on specific lipid compositions. However, the full spectrum of LIPN-related features is still being defined as more cases are identified.