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LIPH
lipase H
The LIPH gene provides instructions for the enzyme lipase H, which plays a critical role in hair follicle development and is associated with inherited hair conditions. The LIPH gene encodes lipase H, an enzyme essential for processing phosphatidic acid into lysophosphatidic acid (LPA).
LIPH is located on the long (q) arm of chromosome 3, at band 3q27.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The LIPH gene, also known as lipase H, is a crucial component in the molecular pathways governing hair growth and development. It provides the genetic blueprint for producing the lipase H enzyme. This enzyme is involved in breaking down specific lipids into signalling molecules vital for cellular processes, particularly within skin and hair follicles.
Dysfunction of the LIPH gene can disrupt these normal processes, leading to inherited conditions primarily characterised by sparse or abnormal hair growth.
What the gene does
The LIPH gene instructs the body to produce lipase H, an enzyme found in various cells and tissues, including the outer layer of skin (epidermis) and sebaceous glands. Its primary function involves the breakdown of phosphatidic acid into lysophosphatidic acid (LPA) and a free fatty acid. LPA functions as a ligand, meaning it binds to specific protein receptors, much like a key fits into a lock. This binding initiates multiple cellular responses.
LPA is integral to many cellular functions, including cell growth and division (proliferation), cell movement (migration), and programmed cell death (apoptosis). Notably, one of LPA's receptors, LPA6 protein, specifically regulates the proliferation and maturation of cells within hair follicles. These cellular activities are fundamental for the proper formation of hair follicles and subsequent hair growth, as continuous cell division pushes the hair shaft upwards and outwards from the skin.
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Chromosome location
The LIPH gene is situated on chromosome 3, specifically at position 3q27.2. This location refers to the long arm (q) of chromosome 3, within band 27.2. The gene spans a region of the human genome that directs the synthesis of a protein composed of 451 amino acids.
Protein structure
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. These changes can range from single nucleotide substitutions to larger deletions or insertions within the gene sequence. Such variants may lead to a non-functional or improperly functioning enzyme, disrupting the biochemical pathways essential for normal hair development.
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 | ★★☆☆ | LIPH-related disorder |
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 | ★★☆☆ | LIPH-related disorder |
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
Mutations in the LIPH gene are associated with various inherited hair conditions. These include autosomal recessive hypotrichosis, characterised by sparse hair growth predominantly on the scalp and sometimes other body areas. Additionally, certain LIPH gene mutations can cause autosomal recessive woolly hair, where individuals have unusually coarse, dry, and tightly curled hair, typically present from birth and mainly affecting scalp hair. In some cases, woolly hair may progress to hypotrichosis in later 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-approved panels within the UK. It is categorised as a green gene for 'Ectodermal dysplasia' (R163) and 'Non-syndromic hypotrichosis' on NHS England's PanelApp, indicating strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the LIPH gene?
The LIPH gene provides instructions for making the enzyme lipase H, which converts phosphatidic acid into lysophosphatidic acid (LPA). LPA is a signalling molecule vital for cellular processes, especially in hair follicle development.
What conditions are associated with LIPH gene mutations?
Mutations in the LIPH gene are linked to inherited hair conditions such as autosomal recessive hypotrichosis, which causes sparse hair, and autosomal recessive woolly hair, characterised by unusually coarse and tightly curled hair.
How does lipase H affect hair growth?
Lipase H produces LPA, which binds to receptors like LPA6 in hair follicles. This interaction is crucial for regulating the proliferation and maturation of hair follicle cells, directly impacting 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