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PROP1
PROP paired-like homeobox 1
The PROP1 gene provides instructions for a transcription factor critical for the development and function of the pituitary gland, a master gland regulating many bodily processes. PROP1, or PROP paired-like homeobox 1, is a gene that encodes a protein essential for the proper development of the pituitary gland.
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 plays a vital role in human development by guiding the formation and function of the pituitary gland, an endocrine gland situated at the base of the brain. This gland is responsible for producing and releasing numerous hormones that regulate growth, metabolism, and reproductive functions. The PROP1 protein acts as a transcription factor, meaning it controls the activity of other genes, specifically those involved in the specialisation of pituitary cells.
What the gene does
The PROP1 gene provides the blueprint for the PROP1 protein, a transcription factor that regulates gene expression within the pituitary gland. This protein is exclusively found in the pituitary, where its primary function is to facilitate the differentiation of cell types. By controlling the activity of other genes, PROP1 ensures the proper development of various hormone-producing cells, including those responsible for growth hormone and thyroid-stimulating hormone. Defects in PROP1 can disrupt this delicate process, leading to deficiencies in multiple pituitary hormones.
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Chromosome location
The PROP1 gene is located on chromosome 5, specifically at position 5q35.3. This precise genomic address helps geneticists and researchers pinpoint its location within the human genome, enabling further study into its structure and function.
Protein structure
The PROP1 protein is composed of 226 amino acids and features distinct structural regions. The N-terminal end, spanning amino acids 1-75, and a C-terminal region, from amino acids 196-226, are both characterised as Disordered regions. A crucial Homeobox domain, responsible for DNA binding, is located between amino acids 69 and 128, enabling the protein to act as a transcription factor.
Key variants
Genetic variations within the PROP1 gene can impact its ability to produce a functional protein, potentially leading to health conditions. These variants, sometimes referred to as mutations, can alter the protein's structure or reduce its expression, thereby impairing pituitary development and hormone production.
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.373C>T | p.Arg125Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency |
c.386_387dup | p.Ser130fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.63del | p.Leu22fs | Pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.74_75dup | p.His26fs | Pathogenic/Likely pathogenic | ★★☆☆ | Pituitary hormone deficiency, combined, 2 |
c.95del | p.Pro32fs | Pathogenic/Likely 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
Changes in the PROP1 gene are associated with combined pituitary hormone deficiency, a condition characterised by the partial or complete absence of two or more hormones produced by the pituitary gland. This typically includes growth hormone, vital for normal growth, and thyroid-stimulating hormone, which regulates the body's metabolism.
No disease links recorded for this gene in our reference set.
UK clinical status
The PROP1 gene is recognised within the UK's NHS genomic testing landscape. It is listed on several green-rated PanelApp panels, indicating strong evidence for its association with conditions such as congenital hypothyroidism (R145), hypogonadotropic hypogonadism (R148), and pituitary hormone deficiency (R159). It is also featured on the DDG2P and IUGR and IGF abnormalities panels.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the function of the PROP1 gene?
The PROP1 gene provides instructions for creating a transcription factor protein that helps pituitary cells specialise and develop correctly. This process is crucial for the pituitary gland to produce and release essential hormones for growth and development.
What health conditions are associated with changes in the PROP1 gene?
Variants in the PROP1 gene are primarily associated with combined pituitary hormone deficiency. This condition involves the reduced or absent production of multiple hormones from the pituitary gland, often including growth hormone and thyroid-stimulating hormone.
Where is the PROP1 gene located in the human genome?
The PROP1 gene is situated on chromosome 5, specifically at the band position 5q35.3. This location helps geneticists identify and study the gene within the context of the entire human genome.
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