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LHCGR
luteinizing hormone/choriogonadotropin receptor
The *LHCGR* gene encodes a receptor protein crucial for responding to luteinizing hormone and chorionic gonadotropin, hormones vital for reproductive system development and function. The *LHCGR* gene provides the blueprint for the luteinizing hormone/chorionic gonadotropin receptor.
LHCGR is located on the short (p) arm of chromosome 2, at band 2p16.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The *LHCGR* gene gives instructions for creating the luteinizing hormone/choriogonadotropin receptor protein. This receptor plays a central role in the human reproductive system by binding to specific hormones, namely luteinizing hormone and chorionic gonadotropin. The interaction between these hormones and their receptor initiates cellular responses that are fundamental for normal sexual development, steroid hormone production, and fertility in both sexes.
What the gene does
The protein produced from the *LHCGR* gene acts as a receptor, meaning it has specific sites that bind to particular signalling molecules, known as ligands. In this case, its ligands are luteinizing hormone (LH) and chorionic gonadotropin (hCG). When these hormones bind to the receptor, they activate pathways within the cell, enabling the body to respond appropriately to these crucial reproductive signals. In males, the receptor's activation in Leydig cells promotes the production of androgens, such as testosterone, which are essential for male sexual development and characteristics. In females, activation of the receptor by LH triggers ovulation, the release of an egg cell from the ovary. During pregnancy, hCG binds to the receptor, helping to maintain the necessary hormonal environment for gestation.
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Chromosome location
The *LHCGR* gene is situated on chromosome 2, specifically at position 2p16.3. This location indicates its precise address within the human genome. The gene spans a region that contributes to the overall structure and organisation of this chromosome.
Protein structure
The LHCGR protein is composed of 699 amino acids. It features a specific domain architecture, including an N-terminal LRRNT domain (amino acids 27-66). Additionally, the protein contains multiple leucine-rich repeats (LRRs): LRR 1 (amino acids 96-115), LRR 2 (amino acids 124-145), LRR 3 (amino acids 149-171), LRR 4 (amino acids 175-196), and LRR 5 (amino acids 198-220), and LRR 6 (amino acids 223-244). These domains are important for the protein's function, particularly in ligand binding and signal transduction.
Key variants
Variants within the *LHCGR* gene can alter the function of the luteinizing hormone/choriogonadotropin receptor. These genetic changes can lead to either an overactive receptor, which is constantly 'on', or a receptor with reduced or absent function, which cannot properly respond to hormonal signals. The specific effect of a variant depends on its nature and location within the gene.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Genetic changes in the *LHCGR* gene are associated with various conditions affecting reproductive development and function. These include familial male-limited precocious puberty, where receptor activation is continuous, leading to early sexual maturation in males. Conversely, Leydig cell hypoplasia, characterised by impaired testosterone production, results from variants that disrupt receptor function. The gene is also relevant to conditions like Polycystic ovary syndrome.
- Polycystic ovary syndrome Dedicated page coming soon
UK clinical status
The *LHCGR* gene is part of the NHS Genomic Medicine Service due to its association with inherited conditions. It is currently featured on the green R146 panel, which focuses on differences in sex development, indicating its clinical relevance in the UK.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the LHCGR gene do?
The *LHCGR* gene provides instructions for making the luteinizing hormone/choriogonadotropin receptor. This receptor is essential for cells to respond to luteinizing hormone and chorionic gonadotropin, which are key hormones for reproductive system development and function in both males and females.
What conditions are associated with variants in the LHCGR gene?
Variants in the *LHCGR* gene can lead to conditions such as familial male-limited precocious puberty, Leydig cell hypoplasia, and are also implicated in Polycystic ovary syndrome. These conditions affect sexual development and fertility due to altered receptor function.
Why is the LHCGR gene important for male reproductive health?
In males, the *LHCGR* gene is critical because its receptor helps Leydig cells in the testes produce androgens like testosterone in response to luteinizing hormone. Testosterone is vital for the development of male sexual characteristics and reproductive organs.
References
- Qiao J, Han B, Liu BL. A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Human mutation. 2009. PMID: 19551906
- Kossack N, Simoni M, Richter-Unruh A. Mutations in a novel, cryptic exon of the luteinizing hormone/chorionic gonadotropin receptor gene cause male pseudohermaphroditism. PLoS medicine. 2008. PMID: 18433292
- Themmen AP, Verhoef-Post M. LH receptor defects. Seminars in reproductive medicine. 2002. PMID: 12428200
- Wu SM, Leschek EW, Rennert OM. Luteinizing hormone receptor mutations in disorders of sexual development and cancer. Frontiers in bioscience : a journal and virtual library. 2000. PMID: 10704433
- Wu SM, Chan WY. Male pseudohermaphroditism due to inactivating luteinizing hormone receptor mutations. Archives of medical research. 1999. PMID: 10714363