On this page
LIPH
lipase H
The LIPH gene provides instructions for producing lipase H, an enzyme vital for breaking down phosphatidic acid into lysophosphatidic acid (LPA), a molecule involved in various cellular processes including hair growth. LIPH encodes lipase H, an enzyme predominantly found in hair follicles and skin, where it facilitates the creation of lysophosphatidic acid (LPA).
LIPH is located on the long (q) arm of chromosome 3, at band 3q27.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 3 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The LIPH gene, also known as lipase H, contains the genetic blueprint for an enzyme called lipase H. This enzyme is crucial across various cells and tissues, particularly in the skin and hair follicles. Its primary function involves processing lipids into signalling molecules essential for normal cellular activities. Understanding LIPH is important for comprehending the genetic basis of certain hair-related conditions.
What the gene does
The LIPH gene directs the synthesis of lipase H, an enzyme responsible for converting phosphatidic acid into lysophosphatidic acid (LPA) and free fatty acid. LPA acts as a signalling molecule by binding to specific receptors, influencing a range of cellular functions such as growth, division, movement, and programmed cell death. One important LPA receptor, LPA6, specifically regulates the proliferation and maturation of cells within hair follicles. These cellular processes are fundamental for the proper development of hair follicles and subsequent hair growth. Lipase H is also found in the epidermis, the outermost layer of the skin, and in sebaceous glands, which produce protective substances for skin and hair.
Video: Genetics 101
Chromosome location
The LIPH gene is situated on chromosome 3 at position 3q27.2. This genomic location specifies where the gene is found within the human genome, providing a precise address for researchers and clinicians studying its role in health and disease.
Protein structure
The lipase H protein consists of 451 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the LIPH gene can alter the function of the lipase H enzyme. More than 15 specific changes in the LIPH gene have been identified that are associated with inherited conditions. These variations can lead to a dysfunctional enzyme or affect the amount of enzyme produced, thereby disrupting the normal cellular processes it regulates.
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.280_369dup | p.Lys123_Thr124insGlyLeuLeuSerValGluAspMetAsnValValValValAspTrpAsnArgGlyAlaThrThrLeuIleTyrThrHisAlaSerSerLys | Pathogenic/Likely pathogenic | ★★☆☆ | Hypotrichosis 7 |
c.328C>T | p.Arg110Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Hypotrichosis 7 |
c.659_660del | p.Ile220fs | Pathogenic | ★★☆☆ | LIPH-related disorder |
c.736T>A | p.Cys246Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Hypotrichosis 7 |
c.742C>A | p.His248Asn | Pathogenic/Likely pathogenic | ★★☆☆ | Hypotrichosis 7 |
c.789del | p.Ser262_Cys263insTer | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
g.(2711_2742)_(3942_3973)del | - | Pathogenic | - | Hypotrichosis 7 |
c.322T>C | p.Trp108Arg | Pathogenic | - | Woolly hair, autosomal recessive 2, with or without hypotrichosis |
c.346_350del | p.Ile116fs | Pathogenic | - | Hypotrichosis 7 |
c.886+405_1094+962del | - | Pathogenic | - | Woolly hair, autosomal recessive 2, with or without hypotrichosis |
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 LIPH gene are primarily linked to inherited hair conditions, including autosomal recessive hypotrichosis and autosomal recessive woolly hair. Autosomal recessive hypotrichosis is characterised by sparse hair growth, often affecting the scalp and sometimes other body areas. Autosomal recessive woolly hair results in hair that is unusually coarse, dry, fine, and tightly curled, typically present from birth and usually affecting only scalp hair. In some instances, individuals with woolly hair may develop hypotrichosis later in life.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic LIPH 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 LIPH gene is included on several NHS Genomic Medicine Service-aligned clinical panels within the UK. It is categorised as 'green' for Ectodermal dysplasia (R163) and Non-syndromic hypotrichosis, indicating that variants in this gene are considered to have a strong association with these conditions and are routinely assessed in a clinical setting.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the LIPH gene?
The LIPH gene provides instructions for making lipase H, an enzyme that converts phosphatidic acid into lysophosphatidic acid (LPA). LPA is a signalling molecule essential for various cellular processes, including cell growth, movement, and particularly hair follicle development.
What conditions are associated with variants in the LIPH gene?
Variants in the LIPH gene are primarily associated with inherited hair conditions such as autosomal recessive hypotrichosis, which causes sparse hair growth, and autosomal recessive woolly hair, characterised by unusually coarse and tightly curled hair.
How does the LIPH gene affect hair growth?
The enzyme produced by the LIPH gene, lipase H, generates lysophosphatidic acid (LPA). LPA interacts with receptors like LPA6 in hair follicles, regulating the proliferation and maturation of cells critical for normal hair development and growth.
References
- Kurban M, Wajid M, Shimomura Y. Mutations in LPAR6/P2RY5 and LIPH are associated with woolly hair and/or hypotrichosis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2013. PMID: 22385360
- Tanahashi K, Sugiura K, Takeichi T. Prevalent founder mutation c.736T>A of LIPH in autosomal recessive woolly hair of Japanese leads to variable severity of hypotrichosis in adulthood. Journal of the European Academy of Dermatology and Venereology : JEADV. 2013. PMID: 22449147
- Khan S, Habib R, Mir H. Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis/woolly hair in 17 consanguineous families from Pakistan. Clinical and experimental dermatology. 2011. PMID: 21426374
- Shinkuma S, Akiyama M, Inoue A. Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA-PLA1alpha in autosomal recessive hypotrichosis. Human mutation. 2010. PMID: 20213768
- Shimomura Y, Wajid M, Petukhova L. Mutations in the lipase H gene underlie autosomal recessive woolly hair/hypotrichosis. The Journal of investigative dermatology. 2009. PMID: 18830268
- Shimomura Y, Wajid M, Zlotogorski A. Founder mutations in the lipase h gene in families with autosomal recessive woolly hair/hypotrichosis. The Journal of investigative dermatology. 2009. PMID: 19262606
- Horev L, Tosti A, Rosen I. Mutations in lipase H cause autosomal recessive hypotrichosis simplex with woolly hair. Journal of the American Academy of Dermatology. 2009. PMID: 19766349