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HOXB13
homeobox B13
The HOXB13 gene provides instructions for a protein that acts as a transcription factor, playing a key role in growth, development, and maintaining normal cell division. HOXB13 is a gene that codes for a transcription factor protein essential for proper cellular development and regulation.
HOXB13 is located on the long (q) arm of chromosome 17, at band 17q21.32. Arm ratio per GRCh38 - banding schematic.
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Overview
The HOXB13 gene, or homeobox B13, is part of the HOX gene family, which are crucial regulators of embryonic development and cellular differentiation. The protein produced from HOXB13 functions as a transcription factor, meaning it controls the activity of other genes. This regulatory role is particularly important in development and maintaining healthy cellular processes [PMID:24077673].
Abnormalities in the HOXB13 gene are associated with an increased susceptibility to hereditary prostate cancer, highlighting its significance in cancer predisposition [PMID:22230915]. Understanding HOXB13's function and genetic variations provides insights into the molecular basis of this inherited condition.
What the gene does
The HOXB13 gene produces a protein classified as a transcription factor, which means it helps regulate the expression of other genes. This regulation occurs by the HOXB13 protein binding to specific DNA sequences, thereby influencing whether certain genes are turned 'on' or 'off'. It is believed to be important in the development and maintenance of various tissues, including the skin [PMID:21206103].
Additionally, the HOXB13 protein is thought to act as a tumour suppressor. In this capacity, it helps prevent uncontrolled cell growth and division. By regulating these fundamental cellular processes, HOXB13 contributes to normal tissue development and helps protect against the formation of tumours. Its role in regulating gene activity is vital for proper biological function [PMID:26034177].
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Chromosome location
The HOXB13 gene is located on chromosome 17 at position 17q21.32. This specific genomic address signifies its precise placement within the long arm (q) of chromosome 17, within region 2, band 1, sub-band 32. This location is shared with several other homeobox genes, forming a cluster that is thought to be functionally related.
Protein structure
The HOXB13 protein consists of 284 amino acids. A defining feature is its Homeobox (DNA binding) domain, which spans amino acids 216-275 and enables the protein to bind to DNA. Within this homeobox region, there are specific segments crucial for DNA interaction: an Interaction with DNA (Region) from amino acids 217-246, another Interaction with DNA (Region) from amino acids 270-273, and an Interaction with 5-mCpG DNA (Region) located between amino acids 258-269. These domains are essential for the protein's function as a transcription factor, allowing it to regulate gene expression by binding to target DNA sequences.
Key variants
Genetic variations within the HOXB13 gene can alter the protein's structure or function, potentially impacting its ability to regulate gene expression and suppress tumour formation. These changes can range from single nucleotide differences to larger insertions or deletions. Certain pathogenic variants in HOXB13 have been identified as contributing to an elevated risk of specific inherited conditions, particularly hereditary prostate cancer [PMID:22230915]. The effect of a variant depends on its specific location and the alteration it causes to the protein.
Sample of pathogenic variants
2 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.251G>A | p.Gly84Glu | Pathogenic/Likely pathogenic; association | ★★☆☆ | HOXB13-related disorder |
c.814A>T | p.Lys272Ter | Pathogenic | - | Gastric cancer |
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
Variations in the HOXB13 gene are primarily associated with an increased genetic predisposition to certain cancers. The most notable conditions linked to HOXB13 are Hereditary prostate cancer and HOXB13-associated prostate cancer. These conditions are typically inherited in an autosomal dominant pattern, meaning that inheriting just one copy of an altered HOXB13 gene is sufficient to increase an individual's risk. Affected individuals may have a family history of prostate cancer, often with an earlier age of onset.
Inheritance pattern
Conditions caused by pathogenic HOXB13 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
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Diet & lifestyle considerations
Research into general lifestyle factors and their interaction with genetic predispositions like those associated with HOXB13 is ongoing. For the general population, maintaining a healthy lifestyle, including a balanced diet rich in fruits and vegetables, regular physical activity, and avoiding smoking, is widely recommended for overall well-being. Some studies suggest a potential link between dietary patterns and prostate cancer risk, but further research is needed to determine specific recommendations for individuals with HOXB13 variants. Individuals with a family history of prostate cancer or known HOXB13 variants should discuss personalised risk management and screening options with their healthcare provider.
Supplement considerations
There is currently no conclusive scientific evidence indicating that specific dietary supplements can prevent or treat conditions associated with HOXB13 gene variants. While some nutrients, such as vitamin D and selenium, have been explored for their potential role in prostate health, the findings are not definitive enough to recommend their use for cancer prevention, especially in the context of specific genetic predispositions. Individuals considering any supplements should consult with a healthcare professional to ensure they are appropriate and safe, particularly if they have underlying health conditions or are taking other medications.
Frequently asked questions
What is the HOXB13 gene?
The HOXB13 gene provides instructions for creating a protein that acts as a transcription factor, controlling the activity of other genes. It is vital for development and helps to prevent uncontrolled cell growth.
What conditions are associated with the HOXB13 gene?
Variations in the HOXB13 gene are associated with an increased risk of Hereditary prostate cancer and HOXB13-associated prostate cancer. These conditions typically follow an autosomal dominant inheritance pattern.
How does HOXB13 contribute to prostate cancer risk?
As a tumour suppressor, the HOXB13 protein normally helps control cell division. Pathogenic variants can impair this function, leading to an increased susceptibility to prostate cancer by disrupting normal cellular regulation.
Is HOXB13-associated prostate cancer hereditary?
Yes, HOXB13-associated prostate cancer is considered hereditary. It is inherited in an autosomal dominant manner, meaning an altered copy of the gene can be passed from one generation to the next, increasing risk in family members.
Can lifestyle changes reduce the risk for individuals with HOXB13 variants?
While a healthy lifestyle is generally beneficial, there is no specific evidence that particular lifestyle changes can definitively counteract the genetic risk conferred by HOXB13 variants. Individuals should consult a healthcare provider for personalised advice and screening.
References
- Huang H, Cai B. G84E mutation in HOXB13 is firmly associated with prostate cancer risk: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2014. PMID: 24026887
- Smith SC, Palanisamy N, Zuhlke KA. HOXB13 G84E-related familial prostate cancers: a clinical, histologic, and molecular survey. The American journal of surgical pathology. 2014. PMID: 24722062
- Lin X, Qu L, Chen Z. A novel germline mutation in HOXB13 is associated with prostate cancer risk in Chinese men. The Prostate. 2013. PMID: 22718278
- Shang Z, Zhu S, Zhang H. Germline homeobox B13 (HOXB13) G84E mutation and prostate cancer risk in European descendants: a meta-analysis of 24,213 cases and 73, 631 controls. European urology. 2013. PMID: 23518396
- Bambury RM, Gallagher DJ. Prostate cancer: germline prediction for a commonly variable malignancy. BJU international. 2012. PMID: 22974436