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GHRHR
growth hormone releasing hormone receptor
The GHRHR gene provides instructions for making the growth hormone releasing hormone receptor, a protein vital for the body's production and release of growth hormone. The GHRHR gene is essential for regulating growth and development through its role in the endocrine system.
GHRHR is located on the short (p) arm of chromosome 7, at band 7p14.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The GHRHR gene, or growth hormone releasing hormone receptor gene, plays a critical role in human growth and development. It encodes a receptor protein that is primarily active in the pituitary gland, a small gland at the base of the brain responsible for producing many hormones, including growth hormone. The proper functioning of this receptor is fundamental for the body's normal growth processes, particularly the development of bones and tissues.
What the gene does
The GHRHR gene provides the blueprint for synthesising the growth hormone releasing hormone receptor. This receptor is located on somatotropic cells within the pituitary gland that produce growth hormone. The receptor's main role is to bind with growth hormone releasing hormone (GHRH), a signalling molecule. This interaction, along with other signals, prompts the somatotropic cells to synthesise and release growth hormone into the bloodstream. Growth hormone then circulates throughout the body, promoting the growth of bones and various tissues, making the GHRHR receptor a crucial part of the endocrine system's growth regulation pathway.
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Chromosome location
The GHRHR gene is situated on chromosome 7, specifically at position 7p14.3. This location refers to the short (p) arm of chromosome 7, within region 14.3. The precise genomic coordinates determine the gene's physical address within the human genome.
Protein structure
The GHRHR protein consists of 423 amino acids.
Key variants
Variants within the GHRHR gene can lead to changes in the structure or function of the growth hormone releasing hormone receptor. These genetic alterations can impact the receptor's ability to bind growth hormone releasing hormone or to initiate the production of growth hormone effectively. Different types of variants may have varying effects on the overall function of the protein, potentially leading to diverse clinical outcomes.
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.1069C>T | p.Arg357Cys | Pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.1089_1093del | p.Leu364fs | Pathogenic | ★★☆☆ | GHRHR-related disorder |
c.1146G>A | p.Glu382= | Pathogenic/Likely pathogenic | ★★☆☆ | GHRHR-related disorder |
c.214G>T | p.Glu72Ter | Pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.280C>T | p.Arg94Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.281G>A | p.Arg94Gln | Pathogenic/Likely pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.431T>A | p.Leu144His | Pathogenic/Likely pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.458C>A | p.Ala153Asp | Pathogenic/Likely pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.481C>T | p.Arg161Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
c.507C>G | p.Phe169Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Isolated growth hormone deficiency, type 4 |
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
Changes in the GHRHR gene are linked to conditions affecting growth. Over 20 distinct genetic alterations within the GHRHR gene have been identified as causative for isolated growth hormone deficiency, a condition marked by slow growth and reduced height. Certain cases of isolated growth hormone deficiency type IB are caused by GHRHR gene mutations. These mutations commonly result in the substitution of a single amino acid within the receptor protein.
No disease links recorded for this gene in our reference set.
UK clinical status
The GHRHR gene is included in several NHS Genomic Medicine Service approved panels in the UK, indicating its clinical relevance for diagnosing specific conditions. It is part of the 'IUGR and IGF abnormalities' panel and the 'Pituitary hormone deficiency' panel (R159), both of which are rated as 'green', signifying that there is strong evidence for the gene's association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the GHRHR gene do?
The GHRHR gene provides instructions for making the growth hormone releasing hormone receptor. This receptor binds to growth hormone releasing hormone, stimulating the pituitary gland to produce and release growth hormone, which is crucial for physical growth and development.
What happens if the GHRHR gene has a variant?
Variants in the GHRHR gene can impair the function of the growth hormone releasing hormone receptor. This can lead to insufficient production and release of growth hormone, resulting in conditions such as isolated growth hormone deficiency, characterised by slow growth and short stature.
Is GHRHR important for general health?
Yes, GHRHR is important for general health, particularly during childhood and adolescence, as it is essential for normal growth and development. Proper functioning of the growth hormone system, regulated by GHRHR, affects bone and tissue development throughout the body.
References
- Alatzoglou KS, Dattani MT. Genetic causes and treatment of isolated growth hormone deficiency-an update. Nature reviews. Endocrinology. 2010. PMID: 20852587
- Mullis PE. Genetics of isolated growth hormone deficiency. Journal of clinical research in pediatric endocrinology. 2010. PMID: 21274339
- Alatzoglou KS, Turton JP, Kelberman D. Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency. The Journal of clinical endocrinology and metabolism. 2009. PMID: 19567534
- Mullis PE. Genetic control of growth. European journal of endocrinology. 2005. PMID: 15762183
- Lin-Su K, Wajnrajch MP. Growth Hormone Releasing Hormone (GHRH) and the GHRH Receptor. Reviews in endocrine & metabolic disorders. 2002. PMID: 12424433