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LPAR6
lysophosphatidic acid receptor 6
The LPAR6 gene provides instructions for a protein vital in regulating hair follicle cell growth and maturation, with variants potentially leading to inherited hair disorders such as hypotrichosis. The LPAR6 gene codes for lysophosphatidic acid receptor 6 (LPA6), a receptor protein primarily found in hair follicles and the outermost layer of skin.
LPAR6 is located on the long (q) arm of chromosome 13, at band 13q14.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The LPAR6 gene, also known as P2RY5, provides genetic instructions for producing the lysophosphatidic acid receptor 6 (LPA6) protein. This protein acts as a receptor, meaning it binds to specific signalling molecules to initiate cellular responses. In the context of hair, LPA6 is the only lysophosphatidic acid (LPA) receptor identified within hair follicles. LPA6's function is critical for the normal development and growth cycle of hair, influencing cell proliferation and differentiation within these specialised skin structures.
What the gene does
The LPAR6 gene encodes a G protein-coupled receptor, LPA6, which is integral to cellular signalling pathways. This receptor specifically binds to lysophosphatidic acid (LPA), a lipid molecule, acting as its ligand. Upon LPA binding, the LPA6 receptor helps regulate key cellular processes, particularly within hair follicles. These processes include the growth and division (proliferation) of cells, as well as their maturation and specialisation (differentiation). The continuous division of cells within hair follicles is essential for pushing the hair shaft upwards and maintaining hair growth. The LPA6 protein is also present in the epidermis, the outermost layer of the skin, suggesting broader roles in skin health beyond just hair growth.
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Chromosome location
The LPAR6 gene is situated on chromosome 13, specifically at position 13q14.2. This location refers to the long (q) arm of chromosome 13, within region 14, band 2. The LPAR6 gene codes for a protein composed of 344 amino acids.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the LPAR6 gene can lead to altered or non-functional LPA6 protein. These changes can disrupt the protein's ability to bind to lysophosphatidic acid or impair its signalling function, thereby affecting the normal regulation of hair follicle development and growth. Over 30 different genetic changes in LPAR6 have been identified that are associated with inherited hair conditions.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in the LPAR6 gene are primarily linked to inherited conditions affecting hair growth and texture. These conditions include autosomal recessive hypotrichosis, characterised by sparse hair on the scalp and sometimes other body parts. Another associated condition is autosomal recessive woolly hair, where individuals present with unusually coarse, dry, and tightly curled hair, often from birth. In some cases, woolly hair can progress to hypotrichosis later in life.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic LPAR6 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 LPAR6 gene is included in UK NHS Genomic Medicine Service national testing through its presence on diagnostic panels. It is listed on PanelApp UK for 'Ectodermal dysplasia' and 'Non-syndromic hypotrichosis', both with a 'green' status, 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 function of the LPAR6 gene?
The LPAR6 gene provides instructions for the LPA6 receptor protein, which binds to lysophosphatidic acid to regulate cell growth and maturation within hair follicles, crucial for normal hair development.
What conditions are associated with variants in the LPAR6 gene?
Variants in the LPAR6 gene are associated with autosomal recessive hypotrichosis, causing sparse hair growth, and autosomal recessive woolly hair, leading to unusually coarse and tightly curled hair.
How is the LPAR6 gene relevant to UK NHS genetic testing?
The LPAR6 gene is part of the UK NHS Genomic Medicine Service national testing, specifically included in panels for 'Ectodermal dysplasia' and 'Non-syndromic hypotrichosis', indicating its clinical significance in the UK.
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
- 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
- Tariq M, Ayub M, Jelani M. Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families. The British journal of dermatology. 2009. PMID: 19292720
- Pasternack SM, von Kügelgen I, Al Aboud K. G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nature genetics. 2008. PMID: 18297070
- Shimomura Y, Wajid M, Ishii Y. Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nature genetics. 2008. PMID: 18297072
- Azeem Z, Jelani M, Naz G. Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). Human genetics. 2008. PMID: 18461368