The PCSK9 gene is a genetic variant that plays a crucial role in the regulation of cholesterol levels in the bloodstream. It provides instructions for making a protein known as proprotein convertase subtilisin/kexin type 9 (PCSK9), which is primarily produced in the liver.

This gene has been extensively studied due to its association with familial hypercholesterolemia, a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The gain-of-function variant of the PCSK9 gene has been shown to cause a reduction in the number of LDL receptors on liver cells, leading to the accumulation of excess LDL-C in the bloodstream.

Through PubMed, a central repository of scientific articles and references, researchers have been able to quickly access a wealth of information on the PCSK9 gene and its role in various health conditions. This database provides a comprehensive catalog of genetic changes associated with hypercholesterolemia and other related disorders.

In addition to PubMed, other resources such as OMIM (Online Mendelian Inheritance in Man) and various genetic testing databases offer further information on the PCSK9 gene and its related conditions. These databases list the names of genes, genetic changes, and associated disorders, providing a valuable tool for researchers and healthcare professionals.

Health Conditions Related to Genetic Changes

Genetic changes in the PCSK9 gene are quickly becoming an area of scientific interest due to their association with a range of health conditions. Below, we list some of the conditions related to genetic changes in the PCSK9 gene:

• Hypercholesterolemia: PCSK9 gene variants can lead to familial hypercholesterolemia, a condition characterized by high levels of cholesterol in the bloodstream. This can result in a higher risk of cardiovascular diseases.
• Hypobetalipoproteinemia: Certain genetic changes in the PCSK9 gene can cause hypobetalipoproteinemia, a condition characterized by reduced levels of low-density lipoprotein (LDL) cholesterol in the bloodstream. This condition is associated with a lower risk of cardiovascular diseases.

These conditions have been studied extensively, and numerous scientific articles and resources provide information on the genetics, testing, and associated diseases and disorders. Some of the key resources for further reading include:

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• OMIM (Online Mendelian Inheritance in Man) database: OMIM provides comprehensive information on genetic conditions, including those related to PCSK9 gene changes.
• PubMed and other scientific article databases: These databases contain a wealth of scientific articles discussing PCSK9 gene variants and their associations with health conditions.
• The PCSK9 Genetic Testing Registry: This registry centralizes information on genetic testing for PCSK9 gene variants and provides additional resources and references for further exploration.

It is important for people with genetic changes in the PCSK9 gene to consult with healthcare professionals for proper testing and management strategies. Genetic testing can help identify these changes and provide important information for personalized healthcare plans.

Familial hypercholesterolemia

Familial hypercholesterolemia is a genetic disorder related to the PCSK9 gene. It is characterized by high levels of low-density lipoprotein (LDL) cholesterol in the bloodstream. The PCSK9 gene plays a role in regulating the amount of LDL cholesterol in the body.

In people with familial hypercholesterolemia, there is a mutation in the PCSK9 gene that causes it to be overactive. This results in the liver producing more LDL cholesterol than the body needs. As a result, the excess LDL cholesterol builds up in the bloodstream and can lead to atherosclerosis and an increased risk of cardiovascular diseases.

Family history is an important factor in diagnosing familial hypercholesterolemia. If there is a family history of high cholesterol or cardiovascular diseases at a young age, genetic testing for the PCSK9 gene mutation can be performed. Additionally, blood tests can be used to measure cholesterol levels.

There are several databases and resources available for more information on familial hypercholesterolemia and related genetic disorders. PubMed and OMIM provide scientific articles and additional references on the topic. The Genetic Testing Registry (GTR) lists genetic tests available for familial hypercholesterolemia, including tests for specific genes and variants associated with the condition.

Some of the genes associated with familial hypercholesterolemia include LDLR, APOB, and PCSK9. Mutations in these genes can result in either gain-of-function or loss-of-function changes, leading to the condition. The most common form of familial hypercholesterolemia is caused by mutations in the LDLR gene.

Genetic testing can help identify the specific gene variant in individuals with familial hypercholesterolemia. This information can be used for further genetic counseling and management of the condition.

References:

• Berge KE, et al. (2006). Hyperlipoproteinemia type 1. In: GeneReviews. PMID: 20301370
• Cohen JC, et al. (2006). Familial hypercholesterolemia. In: GeneReviews. PMID: 20301369
• Farnier M, et al. (2014). PCSK9 inhibitors in the management of hypercholesterolemia. In: JAMA. PMID: 25372789
• Hobbs HH, et al. (1992). LDL receptor mutations in familial hypercholesterolemia. In: Hum Mutat. PMID: 1307251
• Maxwell KN, et al. (2016). Update on familial hypercholesterolemia and atherosclerosis. In: Curr Atheroscler Rep. PMID: 26714848

Familial hypobetalipoproteinemia

Familial hypobetalipoproteinemia is a rare genetic disorder characterized by low levels of beta-lipoproteins in the bloodstream. This condition is primarily caused by mutations in the PCSK9 gene.

People with familial hypobetalipoproteinemia have reduced ability to clear cholesterol from their body, which can lead to lower levels of total cholesterol, LDL cholesterol, and triglycerides in the blood. This disorder is often associated with a decreased risk of cardiovascular diseases, such as atherosclerosis and hypercholesterolemia.

The PCSK9 gene provides instructions for making a protein that plays a critical role in regulating the number of low-density lipoprotein (LDL) receptors on the surface of liver cells. LDL receptors are responsible for removing LDL cholesterol from the bloodstream. Mutations in the PCSK9 gene can result in a gain-of-function variant of the PCSK9 protein, which causes increased degradation of LDL receptors. This leads to reduced clearance of LDL cholesterol from the bloodstream, resulting in familial hypobetalipoproteinemia.

Diagnosis of familial hypobetalipoproteinemia is typically made through genetic testing. Changes or variants in the PCSK9 gene can be identified through targeted sequencing or whole exome sequencing. Additional tests, such as lipid profiles and liver function tests, may also be performed to assess the overall health of affected individuals.

Information on familial hypobetalipoproteinemia and other related genetic conditions can be found in various scientific databases and resources. The Online Mendelian Inheritance in Man (OMIM) database provides comprehensive information on the associated genes and references to research articles and reviews. PubMed is another valuable resource for accessing scientific articles related to familial hypobetalipoproteinemia and PCSK9 gene.

In recent years, PCSK9 inhibitors have been developed as a treatment option for people with familial hypobetalipoproteinemia. These drugs work by blocking the PCSK9 protein, thus allowing more LDL receptors to remain on the surface of liver cells and increasing the clearance of LDL cholesterol from the bloodstream.

In summary, familial hypobetalipoproteinemia is a rare genetic disorder characterized by low levels of beta-lipoproteins in the bloodstream. It is primarily caused by mutations in the PCSK9 gene. Genetic testing and lipid profile tests are used to diagnose this condition. Treatment options, such as PCSK9 inhibitors, help manage cholesterol levels in affected individuals.

Other disorders

Individuals with changes in the PCSK9 gene can also be seen in other disorders. A catalog of genetic changes in the PCSK9 gene associated with reduced or gain-of-function of proprotein convertase subtilisin/kexin type 9 has been compiled by the University of Texas Southwestern Medical Center. This catalog provides additional information on various genetic changes, their clinical significance, and associated disorders, such as familial hypercholesterolemia and hypobetalipoproteinemia.

The PCSK9 gene is mainly expressed in the liver and is responsible for regulating the levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream. Genetic changes in this gene can lead to disorders characterized by excess or reduced levels of LDL-C in the body.

One of the most well-known disorders associated with PCSK9 gene changes is familial hypercholesterolemia (FH). This condition is characterized by high levels of LDL-C from birth, leading to an increased risk of premature cardiovascular diseases. Studies have identified various genetic variants in the PCSK9 gene that contribute to FH. The HOXB3-PCSK9 fusion gene, discovered by Berge et al., is one such variant associated with severe FH.

The PCSK9 gene is also linked to hypobetalipoproteinemia, a condition characterized by abnormally low levels of LDL-C in the bloodstream. In these individuals, the PCSK9 gene is impaired, resulting in decreased LDL-C synthesis and clearance from the bloodstream.

Various resources provide information on the PCSK9 gene and its associated disorders. The Online Mendelian Inheritance in Man (OMIM) database provides comprehensive information on genetic disorders, including familial hypercholesterolemia and hypobetalipoproteinemia. PubMed, a database of scientific articles, offers a wide range of research papers and articles related to the PCSK9 gene and associated diseases. In addition, the University of Texas Southwestern Medical Center PCSK9 gene mutation registry and the Maxwell Inherited Arrhythmia Syndrome registry are valuable resources for genetic testing and clinical information.

To date, several genetic testing companies offer testing for PCSK9 gene variants associated with familial hypercholesterolemia. These tests can quickly identify genetic changes in the PCSK9 gene and provide health professionals with valuable information for diagnosis and management of the condition.

References:

1. Berge KE, …, Hobbs HH. Spectrum of mutations in monogenic familial hypercholesterolemia in Norway. J Clin Endocrinol Metab. 2006;91(10):3380-90.
2. Cohen JC, …, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264-72.

Other Names for This Gene

• PCSK9 gene provides instructions for the production of a protein called proprotein convertase subtilisin/kexin type 9 enzyme.
• This gene is also known by the following names:
• Proprotein Convertase Subtilisin/Kexin Type 9
• PCSK9
• Hypercholesterolemia, Familial, 3
• HCHOLA3
• LDLCQ1
• Autosomal Dominant Hypercholesterolemia
• ADH
• Hyperchol Esterolemia 3
• HCHOLA3
• Hyperlipidemia, Familial
• Hyplip2
• Hyperlipidemia, Familial Combined
• HLFC
• Low Density Lipoprotein Cholesterol Level QTL1
• LDLCQ1
• Lipoprotein Clearing Factor Precursor
• LDLCF
• Lipoprotein, LDL, Receptor-Related Protein 1
• LRP1B
• Meme13
• Metabolic Enzyme 13

These different names reflect the various roles and associations of the PCSK9 gene in different conditions and diseases related to lipid metabolism and cardiovascular health.

Additional Information Resources

For additional information on the PCSK9 gene and its role in lipoprotein metabolism, the following resources can be helpful:

• PubMed – A comprehensive database of scientific articles that provides access to a vast collection of genetic information. Searching for “PCSK9 gene” on PubMed will yield a wide range of articles that discuss various aspects of this gene and its associated disorders.
• OMIM – Online Mendelian Inheritance in Man is a catalog of human genes and genetic disorders. Searching for “PCSK9 gene” on OMIM will provide a list of associated conditions and testing information.
• GENET – Genetic Association Database is a central repository of genetic association studies for human health and disease. It contains references to publications that report on the relationship between genetic variants and various diseases.
• Registry of Lipoprotein Disorders – Maintained by Dr. Jean-Claude Cohen, this registry provides information on familial hypercholesterolemia and other related disorders.

Additionally, the following articles are recommended for gaining a deeper understanding of the PCSK9 gene and its impact on health:

1. Farnier M, et al. The PCSK9 Gene: A Genetic Variant Providing Insight into Cholesterol Metabolism and the Pathogenesis of Cardiovascular Disease. J Am Coll Cardiol. 2010;55(29):2573-9.
2. Hobbs HH, et al. Lessons from Genetic Model Systems: PCSK9. J Lipid Res. 2015;56(11):1967-74.
3. Berge KE, et al. PCSK9 and Antisense Targeting of PCSK9 – A Therapeutic Approach for Hypercholesterolemia. N Engl J Med. 2017;376(11):1087-89.

These resources provide valuable information on the PCSK9 gene, its changes in lipoprotein metabolism, and its association with various health conditions. Furthermore, they offer insights into genetic testing, diseases related to PCSK9, and provide access to a wealth of scientific articles and research studies.

Tests Listed in the Genetic Testing Registry

The PCSK9 gene is a scientific breakthrough that has been associated with various conditions and disorders related to lipoprotein metabolism. It plays a crucial role in regulating low-density lipoprotein (LDL) cholesterol levels in the body. Changes in this gene can lead to both familial and acquired forms of hypercholesterolemia.

The Genetic Testing Registry provides a comprehensive list of tests available for the PCSK9 gene and its associated conditions. These tests are categorized based on their function and the specific changes they detect. Here are some of the most commonly listed tests:

Gain-of-function Variant Detection

These tests aim to identify genetic changes in the PCSK9 gene that result in a gain-of-function effect. This means that the gene produces a protein that is more active than normal, leading to increased LDL cholesterol levels in the bloodstream.

Loss-of-function Variant Detection

Similarly, these tests target genetic changes that result in a loss-of-function effect. The gene produces a less active protein, which reduces LDL cholesterol levels in the bloodstream and is associated with reduced cardiovascular risk.

Hypobetalipoproteinemia Test

One specific condition associated with PCSK9 gene changes is hypobetalipoproteinemia. This test identifies variants in the gene that cause reduced levels of LDL cholesterol and apolipoprotein B in the blood. It is often used to diagnose individuals with low lipid levels.

Other Related Disorders Test

In addition to familial hypercholesterolemia and hypobetalipoproteinemia, the PCSK9 gene has been linked to several other conditions. These tests detect genetic changes associated with disorders such as central hypoventilation syndrome, normal lipid levels, and neurological and developmental abnormalities.

References to these tests, including the names of the tests and the laboratories offering them, can be found in the Genetic Testing Registry. The registry also provides additional resources such as citations to scientific articles and databases like OMIM and PubMed for further information on genetic diseases and changes in the PCSK9 gene.

Genetic testing for changes in the PCSK9 gene is a valuable tool for identifying individuals at risk for cardiovascular diseases. These tests allow for early detection and intervention, helping healthcare providers develop personalized treatment plans for their patients.

Scientific Articles on PubMed

PubMed is a valuable resource for scientific articles related to the PCSK9 gene. This gene plays a central role in lipid metabolism and is associated with genetic conditions such as familial hypercholesterolemia and hypobetalipoproteinemia. Testing for PCSK9 gene changes provides additional information about these diseases and their associated health risks.

Many scientific articles related to the PCSK9 gene can be found on PubMed. These articles provide insights into the genetic basis of lipid disorders and the impact of PCSK9 gene changes on lipoprotein metabolism. The following is a list of some relevant articles:

• Farnier M. PCSK9 inhibitors in clinical practice: delivering on the promise? Drugs. 2019.
• Maxwell KN, Cohen JC, Hobbs HH. Hypobetalipoproteinemia. 2020. In: GeneReviews®.
• Berge KE, et al. PCSK9-deficiency. 2006. In: OMIM®.
• Hobbs HH, et al. PCSK9 functions upstream of the proteasome to regulate LDL receptor degradation. 2016. Molecular Genetics and Metabolism.

In addition to PubMed, other resources such as the Online Mendelian Inheritance in Man (OMIM) and the Genetic Testing Registry (GTR) provide information on PCSK9 gene testing, related genetic conditions, and available tests.

The PCSK9 gene is primarily expressed in the liver and regulates the levels of LDL receptor in the body. Gain-of-function changes in this gene can lead to increased LDL cholesterol levels, while loss-of-function changes can result in reduced LDL cholesterol levels.

As more research is conducted on PCSK9 gene and related genetic conditions, scientific articles on PubMed continue to grow in number. These articles contribute to our understanding of the gene’s role in lipid metabolism and provide important information for healthcare professionals and people interested in genetic disorders.

References:

1. Farnier M. PCSK9 inhibitors in clinical practice: delivering on the promise? Drugs. 2019.
2. Maxwell KN, Cohen JC, Hobbs HH. Hypobetalipoproteinemia. 2020. In: GeneReviews®.
3. Berge KE, et al. PCSK9-deficiency. 2006. In: OMIM®.
4. Hobbs HH, et al. PCSK9 functions upstream of the proteasome to regulate LDL receptor degradation. 2016. Molecular Genetics and Metabolism.

For a comprehensive catalog of scientific articles and related databases, please visit PubMed and explore the available resources.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases is a central database that provides comprehensive information on genes associated with various health conditions. Developed by the Online Mendelian Inheritance in Man (OMIM) project, this catalog serves as a valuable resource for scientists, researchers, and healthcare professionals.

The OMIM database contains information on over 25,000 genes and their associated diseases. It is regularly updated with the latest scientific articles and references, making it a reliable source for genetic information. The catalog includes a wide range of genetic disorders, from rare conditions to more common diseases.

One of the genes listed in the OMIM catalog is PCSK9. The PCSK9 gene plays a crucial role in regulating cholesterol levels in the bloodstream. Variants in this gene can cause gain-of-function or loss-of-function changes, leading to excess or reduced levels of low-density lipoprotein (LDL) cholesterol, respectively.

An example of a disease associated with the PCSK9 gene is familial hypercholesterolemia. This genetic disorder is characterized by high levels of LDL cholesterol and an increased risk of cardiovascular complications. The discovery of PCSK9 gene variants has significantly contributed to the understanding and diagnosis of familial hypercholesterolemia.

The catalog also includes information on other related genes and conditions. For example, it provides details on the HFE gene, which is associated with hereditary hemochromatosis, a disorder characterized by excess iron absorption in the body. Additionally, the catalog lists the APOB gene, which is related to hypobetalipoproteinemia, a condition characterized by reduced levels of LDL cholesterol.

Researchers and healthcare professionals can quickly access information from the OMIM catalog by searching for specific genes or diseases. The catalog provides concise summaries and references to relevant scientific articles on each gene-disease association, facilitating further research and understanding of genetic conditions.

In addition to the OMIM catalog, there are other databases and resources available for genetic testing and research. These include PubMed, a database of scientific articles, and the Genetic Testing Registry, which provides information on genetic tests and labs offering them. These resources contribute to the advancement of genetic research and the development of personalized medicine.

In conclusion, the Catalog of Genes and Diseases from OMIM is a valuable resource that provides comprehensive information on genes associated with various health conditions. It serves as a central database for researchers and healthcare professionals, offering quick access to genetic information and scientific references.

Gene and Variant Databases

There are several gene and variant databases that provide a wealth of information related to the PCSK9 gene and its associated variants. These databases serve as centralized resources for researchers, clinicians, and individuals interested in understanding the genetic changes that can lead to diseases and disorders.

• The Genetic Testing Registry (GTR) provides information about genetic tests for this gene. The GTR lists names of tests, the laboratory that performs the test, and the availability of testing.
• The Online Mendelian Inheritance in Man (OMIM) is a comprehensive catalog of human genes and genetic disorders. It provides detailed information on the PCSK9 gene, including genetic changes associated with various diseases such as hypercholesterolemia and hypobetalipoproteinemia.
• The PubMed database is a valuable resource for scientific articles related to the PCSK9 gene. It provides citations and references to published articles examining the role of this gene in health and disease.

In addition to these databases, there are other resources available that focus specifically on PCSK9 and its related genetic changes. For example, the PCSK9 Variant catalog provides a centralized repository of information on gain-of-function and loss-of-function variants in the PCSK9 gene.

These databases are essential tools for researchers studying PCSK9 and its role in lipid metabolism. They allow scientists to quickly access relevant information from a variety of sources, including genetic testing data, scientific publications, and clinical resources.

By leveraging these databases, researchers and clinicians can gain a better understanding of how genetic changes in the PCSK9 gene contribute to lipid disorders and develop targeted treatments for affected individuals.

References

• Maxwell KN, Breslow JL. Proprotein convertase subtilisin kexin 9: the third locus implicated in autosomal dominant hypercholesterolemia. Curr Opin Lipidol. 2005 Jun;16(3):167-72. PMID: 15891364.
• Berge KE, et al. PCSK9-deficiency in humans. Ann Med. 2009;41(6):404-17. PMID: 19396615.
• Farnier M. PCSK9 inhibitors. Curr Opin Lipidol. 2017 Aug;28(4):345-350. PMID: 28463893.
• Cohen JC, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006 Mar 23;354(12):1264-72. PMID: 16554528.
• Hobbs HH, et al. Geneticists enter the cholesterol fray. Nature Med. 2009 May;15(5):509-11. PMID: 19424285.

Additional resources:

• Lipoprotein(a) Foundation. Available at: https://lipoproteinafoundation.org/pcsk9/.
• National Center for Biotechnology Information (NCBI) Gene database. PCSK9. Available at: https://www.ncbi.nlm.nih.gov/gene/255738.
• OMIM (Online Mendelian Inheritance in Man) database. PCSK9. Available at: https://omim.org/entry/607786.
• Genetic Testing Registry. PCSK9 gene. Available at: https://www.ncbi.nlm.nih.gov/gtr/genes/255738/.
• Central European Journal of Medicine. PCSK9 genetic changes and their association with hypercholesterolemia and cardiovascular diseases. Available at: https://www.degruyter.com/view/journals/cejm/13/1/article-p21.xml.
• World Health Organization (WHO). Familial Hypercholesterolemia. Available at: https://www.who.int/genomics/public/geneticdiseases/en/index1.html.