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PROP1
PROP paired-like homeobox 1
The PROP1 gene provides instructions for making a protein that is essential for the proper development and function of the pituitary gland, a key endocrine organ. PROP1 encodes a transcription factor found exclusively in the pituitary gland, where it regulates the activity of other genes.
PROP1 is located on the long (q) arm of chromosome 5, at band 5q35.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The PROP1 gene, also known as PROP paired-like homeobox 1, is crucial for the normal development and function of the pituitary gland. This gland, located at the base of the brain, produces and releases various hormones that regulate growth, metabolism, and reproduction.
The protein produced from the PROP1 gene acts as a transcription factor, meaning it controls the expression of other genes. Its specific role in the pituitary gland is to help different cell types develop and specialise, which is essential for the gland to produce its full range of hormones.
What the gene does
The PROP1 gene directs the synthesis of a protein that functions as a transcription factor. This protein's primary role is to bind to specific DNA sequences, thereby regulating the activity of other genes. Within the human body, the PROP1 protein is found exclusively in the pituitary gland.
In this specialised endocrine gland, the PROP1 protein is vital for cellular differentiation. It helps pituitary cells develop into their distinct types, each responsible for producing particular hormones. These hormones are critical for a wide array of bodily functions, including growth, metabolism, and reproductive processes. Without proper PROP1 function, the pituitary gland may fail to produce adequate levels of multiple essential hormones.
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Chromosome location
The PROP1 gene is located on the long (q) arm of chromosome 5 at position 35.3, also written as 5q35.3. This specific genomic location places PROP1 within a region of the chromosome that contains various genes essential for development and physiological processes.
Protein structure
The PROP1 protein consists of 226 amino acids and features several distinct regions. The N-terminal portion, from amino acids 1-75, is characterised as a Disordered region. This is followed by a Homeobox domain, spanning amino acids 69-128, which is critical for DNA binding and its function as a transcription factor. Another Disordered region is present at the C-terminus, from amino acids 196-226.
Key variants
Genetic variations, or variants, within the PROP1 gene can impact its ability to produce a functional protein. These changes can disrupt the gene's instructions, leading to altered or non-functional PROP1 protein. The consequences of such variants can range from mild to severe, depending on how significantly the protein's function is impaired.
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.109+1G>A | - | Pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.109+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.129dup | p.Arg44fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.156dup | p.Arg53fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.211C>T | p.Arg71Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.2T>C | p.Met1Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.373C>T | p.Arg125Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency |
c.386_387dup | p.Ser130fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.390_391del | p.Leu131fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.63del | p.Leu22fs | Pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
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 PROP1 gene are primarily associated with conditions affecting pituitary hormone production. When the PROP1 protein is faulty or absent, the pituitary gland may not develop correctly or produce sufficient amounts of its hormones. This can lead to a deficiency in two or more pituitary hormones, impacting several bodily systems.
No disease links recorded for this gene in our reference set.
UK clinical status
The PROP1 gene is included in several NHS Genomic Medicine Service (GMS) approved panels, indicating its clinical relevance in the UK. It is a 'green' gene on PanelApp for conditions such as Congenital hypothyroidism (R145), Hypogonadotropic hypogonadism (R148), IUGR and IGF abnormalities, and Pituitary hormone deficiency (R159). It is also listed within the DDG2P panel, further highlighting its importance in diagnosing developmental disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the pituitary gland and why is PROP1 important for it?
The pituitary gland is a small endocrine gland at the base of the brain that produces hormones crucial for growth, metabolism, and reproduction. The PROP1 gene makes a protein that helps pituitary cells specialise, ensuring the gland can produce these vital hormones effectively.
What happens if the PROP1 gene doesn't work correctly?
If the PROP1 gene is not working as it should, the pituitary gland may not develop properly or produce enough of its hormones. This can lead to a deficiency in multiple pituitary hormones, affecting various aspects of bodily function and development.
How does the PROP1 protein regulate other genes?
The PROP1 protein acts as a transcription factor. This means it binds directly to specific regions of DNA to control whether other genes are switched on or off, thereby regulating their activity and the production of their associated proteins.
References
- Kelberman D, Turton JP, Woods KS. Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD). Clinical endocrinology. 2009. PMID: 19128366
- Kelberman D, Rizzoti K, Lovell-Badge R. Genetic regulation of pituitary gland development in human and mouse. Endocrine reviews. 2009. PMID: 19837867
- Lemos MC, Gomes L, Bastos M. PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency. Clinical endocrinology. 2006. PMID: 16984240
- Mody S, Brown MR, Parks JS. The spectrum of hypopituitarism caused by PROP1 mutations. Best practice & research. Clinical endocrinology & metabolism. 2002. PMID: 12464226