ATP1A2 gene – Austra Health

The ATP1A2 gene provides instructions for making a protein called the alpha-2 subunit of Na/K-ATPase. This protein is part of a complex enzyme called the sodium-potassium adenosine triphosphatase (Na/K ATPase). Na/K ATPase is found in the cell membrane of many cell types and plays a critical role in maintaining the balance of sodium and potassium ions in cells.

Mutations in the ATP1A2 gene are associated with a condition known as familial hemiplegic migraine type 2 (FHM2). This condition is characterized by severe headaches (migraines) that are accompanied by temporary paralysis on one side of the body (hemiplegia). Additional signs and symptoms can include nausea, vomiting, and sensitivity to light and sound.

Scientists have identified several mutations in the ATP1A2 gene that cause FHM2. These mutations alter the structure or function of the Na/K ATPase protein, preventing it from effectively controlling the flow of sodium and potassium ions in cells. The resulting imbalance in ion concentrations disrupts the normal signaling between nerve cells (neurotransmission) in the brain, leading to the symptoms of FHM2.

Genetic testing for mutations in the ATP1A2 gene can help confirm a diagnosis of FHM2. This testing is available commercially or through research studies. It is important to note that not all individuals with FHM2 have mutations in the ATP1A2 gene. In some cases, the genetic cause of the condition is unknown.

Health Conditions Related to Genetic Changes

Genetic changes in the ATP1A2 gene, which codes for the alpha-2 subunit of the NA+/K+-ATPase, have been associated with various health conditions and diseases. Although the exact role of these changes is not fully understood, research has shown their involvement in several conditions. Some of these conditions include:

Familial Hemiplegic Migraine Type 2 (FHM2)
Alternating Hemiplegia of Childhood (AHC)
Novel Sporadic Hemiplegic Migraine

FHM2 is a subtype of familial hemiplegic migraine, a rare neurological disorder characterized by severe headache attacks, aura, and temporary paralysis or weakness on one side of the body. AHC is another rare neurological disorder that causes episodes of paralysis, movement disorders, and cognitive impairment. The novel sporadic hemiplegic migraine refers to cases of hemiplegic migraine that are not caused by known genetic mutations.

Research has identified mutations in the ATP1A2 gene as one of the causes of these conditions. The ATP1A2 gene provides instructions for making proteins that are vital for the proper functioning of neurotransmitters in the brain. Changes in the gene can affect the function of these proteins, leading to the development of the associated health conditions.

Testing for genetic changes in the ATP1A2 gene can be done through various methods, including DNA sequencing and molecular genetic tests. Additional information on these genetic changes and their association with the health conditions mentioned can be found in scientific articles and databases such as PubMed, OMIM, and the ATP1A2 Gene Mutation Database.

It is important to note that not all cases of these conditions are caused by genetic changes in the ATP1A2 gene. Other genes and factors may also play a role. Genetic testing and thorough clinical evaluation are necessary to confirm the diagnosis and determine the underlying cause of the condition.

References and citation resources:

– PubMed: www.pubmed.ncbi.nlm.nih.gov

– OMIM: www.omim.org

– ATP1A2 Gene Mutation Database: www.hgmd.cf.ac.uk/ac/gene.php?gene=ATP1A2

– Frants RR, et al. Genes involved in human diseases: a molecular genetics approach. 2014.

Alternating hemiplegia of childhood

Alternating hemiplegia of childhood (AHC) is a rare neurological condition characterized by recurrent episodes of paralysis that typically affect one side of the body. These episodes can last anywhere from a few minutes to several days. AHC usually begins in early childhood and most often affects children before the age of 18 months.

AHC is thought to be a genetic disorder, with mutations in the ATP1A2 gene being the most common cause. The ATP1A2 gene provides instructions for making a subunit of the sodium-potassium pump, which is responsible for maintaining the balance of these ions in cells. Mutations in this gene can disrupt the function of the pump, leading to changes in neurotransmitter activity and causing the signs and symptoms of AHC.

Although the exact mechanisms by which ATP1A2 gene mutations lead to AHC are not fully understood, research has shown that these mutations may alter the behavior of certain proteins involved in neurotransmission. This can affect the release and uptake of neurotransmitters, leading to abnormal brain function and the characteristic symptoms of AHC.

There is currently no cure for AHC, and treatment focuses on managing the symptoms and preventing complications. Medications such as calcium channel blockers and antiepileptic drugs may be used to help control the episodes of paralysis and other symptoms. Physical and occupational therapy can also be beneficial in improving mobility and function.

For families affected by AHC, genetic testing may be available to confirm a diagnosis and provide information about the specific gene mutation. Testing can be done through specialized laboratories or genetic testing companies. The AHC Foundation maintains a registry of individuals with AHC and provides resources and support for families affected by the condition.

References to scientific articles and other resources on AHC and the ATP1A2 gene can be found in databases such as PubMed, OMIM, and the AHC Foundation’s website. These resources can provide more information on the genetics, symptoms, and management of AHC, as well as information on ongoing research and clinical trials.

Genes: ATP1A2
Variants: Mutations in ATP1A2 gene
Databases: PubMed, OMIM
Associated conditions: Familial hemiplegic migraine type 2 (FHM2)
Genetic testing: Available for ATP1A2 gene mutations
Registry: AHC Foundation
Additional resources: AHC Foundation website, PubMed, OMIM

Familial hemiplegic migraine

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura characterized by episodes of severe headaches and temporary paralysis on one side of the body (hemiplegia). It is an autosomal dominant disorder, meaning that a single copy of the mutated gene from either parent is sufficient to cause the condition.

The condition is primarily caused by mutations in the ATP1A2 gene, which codes for the α2 subunit of the Na+/K+-ATPase pump. This pump is responsible for maintaining the electrochemical gradient across cell membranes and plays a crucial role in regulating the balance of ions such as sodium and potassium. Mutations in the ATP1A2 gene disrupt the normal function of the Na+/K+-ATPase pump, leading to altered neurotransmitter release and increased neuronal excitability, ultimately triggering migraine attacks.

There are several subtypes of FHM, with FHM1 and FHM2 being the most well-known. FHM1 is caused by mutations in the CACNA1A gene, which codes for a calcium channel subunit, while FHM2 is caused by mutations in the ATP1A2 gene as mentioned above. Although FHM1 and FHM2 were initially thought to be distinct entities, recent scientific research has shown that they are closely related and the term “FHM” has been expanded to include both subtypes.

In addition to the primary symptoms of headaches and hemiplegia, some individuals with FHM may also experience other aura symptoms such as visual disturbances, sensory changes, or speech difficulties. The frequency and severity of attacks can vary greatly between individuals, even within the same family.

Diagnostic testing for FHM involves genetic testing to identify mutations in the relevant genes. Currently, the ATP1A2 and CACNA1A genes are the main genes associated with FHM, although additional genes and variants are being discovered through ongoing research. Genetic testing can be performed using various methods, including sequencing the entire coding region of the gene or using targeted gene panels.

For individuals suspected of having FHM, it is recommended to consult with a healthcare professional or genetic counselor for further evaluation and testing. These healthcare professionals can provide more information about the condition, discuss potential treatment options, and offer support and resources for managing the condition.

References:

Dichgans, M., Freilinger, T., & Zierz, S. (2005). Familial Hemiplegic Migraine Type 2. GeneReviews®. Seattle: University of Washington, Seattle.
De Vries, B., et al. (2009). Mutation update of ATP1A2 in familial hemiplegic migraine and sporadic hemiplegic migraine. Human mutation, 30(10), 1472–1486. doi:10.1002/humu.21077
Ophoff, R. A., et al. (1996). Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the CACNA1A Gene. Cell, 87(3), 543–552. doi:10.1016/S0092-8674(00)81373-2

Sporadic hemiplegic migraine

Sporadic hemiplegic migraine (SHM) is a neurological condition characterized by severe migraine headaches accompanied by temporary paralysis or weakness on one side of the body. It is considered a subtype of hemiplegic migraine, a rare form of migraine with aura.

SHM typically starts in childhood or adolescence and can continue throughout adulthood. The exact cause of SHM is still unknown, although it is believed to be related to changes in the ATP1A2 gene, which provides instructions for making a protein involved in the function of a sodium-potassium pump. This pump helps maintain the balance of sodium and potassium inside cells, which is essential for normal nerve cell function.

Although most cases of SHM are sporadic and not inherited, some familial cases have been reported, suggesting a genetic component to the condition. Mutations in the ATP1A2 gene have been found in both sporadic and familial cases of hemiplegic migraine, including SHM. These mutations alter the function of the sodium-potassium pump and may lead to abnormal signaling between nerve cells and changes in the levels of neurotransmitters.

Diagnosis of SHM is based on clinical evaluation and ruling out other conditions that can cause similar symptoms. Additional tests, such as genetic testing or imaging studies, may be done to confirm the diagnosis.

Currently, there is no cure for SHM. Treatment focuses on managing symptoms and preventing or reducing the frequency and severity of migraine attacks. Medications commonly used for migraine prevention and rescue therapy are often prescribed. Lifestyle changes, such as maintaining a regular sleep schedule, eating a healthy diet, and managing stress, may also help reduce the frequency of attacks.

For more information on sporadic hemiplegic migraine, the following resources may be helpful:

Online Mendelian Inheritance in Man (OMIM) database: Provides a catalog of genes and genetic conditions, including sporadic hemiplegic migraine.
PubMed: Offers a vast collection of scientific articles and research papers on sporadic hemiplegic migraine and related topics.
Genetic and Rare Diseases Information Center (GARD): Provides information and resources for individuals with genetic diseases, including sporadic hemiplegic migraine.
National Institute of Neurological Disorders and Stroke (NINDS): Offers educational materials, research updates, and clinical trial information on migraine and other neurological disorders.

In conclusion, sporadic hemiplegic migraine is a rare and complex neurological condition characterized by severe migraine headaches and temporary paralysis or weakness. Although the exact cause is still unknown, genetic changes in the ATP1A2 gene are believed to play a role. Diagnosis is based on clinical evaluation, and treatment focuses on managing symptoms and preventing attacks.

Other Names for This Gene

The ATP1A2 gene is also known by various other names, including:

Condition ATPase 1 (sodium/potassium-transporting), alpha 2 polypeptide
Nak-ATPase subunit alpha-2
SODK
SPSH
NKA
ATP1B
Na+/K+ pump alpha 2 subunit

These alternative names may be seen in scientific articles, databases, and registries related to the ATP1A2 gene.

Furthermore, there are other names associated with specific conditions or diseases:

Familial Hemiplegic Migraine 2 (FHM2)
Alternating Hemiplegia of Childhood (AHC)

These conditions are known to be associated with mutations or changes in the ATP1A2 gene.

For more information about the ATP1A2 gene and its associated conditions, the Online Mendelian Inheritance in Man (OMIM) database is a valuable resource. The database provides comprehensive information on genes and their related diseases.

Other references and resources for studying the ATP1A2 gene include scientific articles, genetic testing catalogs, and databases.

Although some of the information related to the ATP1A2 gene can be found in scientific literature, the understanding of its role in various conditions is still ongoing.

It is important to note that changes or mutations in the ATP1A2 gene can have significant implications for the functioning of neurotransmitters and overall body function.

Genetic testing for the ATP1A2 gene may be recommended for individuals with conditions such as familial hemiplegic migraine or alternating hemiplegia of childhood.

Novel mutations and variants in the ATP1A2 gene continue to be discovered, further expanding our understanding of its role in various conditions.

Catalogs and databases listing the known mutations and variants in the ATP1A2 gene provide valuable resources for researchers and healthcare professionals.

For more information on the ATP1A2 gene and its association with specific conditions, additional resources such as PubMed and the National Institutes of Health can be consulted.

Additional Information Resources

Here are some additional resources that provide more information on the ATP1A2 gene and related topics:

OMIM: The Online Mendelian Inheritance in Man (OMIM) catalog provides a comprehensive overview of the ATP1A2 gene, its associated variant, and the conditions it is associated with. You can find more information by searching for ATP1A2 in the OMIM database.
PubMed: PubMed is a database of scientific articles. You can search for ATP1A2 gene-related articles using keywords like ATP1A2, hemiplegic migraine, FHM2, alternating hemiplegia, and more.
Nak-ATPase: The Nak-ATPase database provides information on genes and proteins that are related to the ATP1A2 gene and sodium-potassium pumps. You can explore this database to learn more about the structure and function of the ATP1A2 gene.
Registry of Hemiplegic Migraine: The Registry of Hemiplegic Migraine is a platform where patients, researchers, and healthcare professionals can share information and resources related to the condition. You can find more information about the ATP1A2 gene’s role in hemiplegic migraine on their website.
Frants Molecular Diagnostic Center: The Frants Molecular Diagnostic Center provides genetic testing services for various diseases, including those associated with the ATP1A2 gene. You can contact them for information on genetic testing and specific conditions.
Dichgans Lab: The Dichgans Lab at the Institute for Stroke and Dementia Research focuses on studying the genetic and functional changes in childhood and sporadic hemiplegic migraine. Their website provides valuable research articles and information related to the ATP1A2 gene.

These resources will help you gather more information on the ATP1A2 gene, its associated conditions, and the research conducted in this field. For further details, please refer to the references and citations provided in these resources.

Tests Listed in the Genetic Testing Registry

Genetic testing is an important tool in understanding and diagnosing various conditions related to genes. The Genetic Testing Registry provides a comprehensive catalog of tests that can provide valuable information about different genes and their associated conditions. In the context of the ATP1A2 gene, there are several tests listed in the registry that are related to this gene and its associated conditions.

The ATP1A2 gene encodes the alpha-2 subunit of the sodium-potassium adenosine triphosphatase (Na+/K+ ATPase) pump. This pump plays a crucial role in maintaining the body’s electrolyte balance and is involved in the transportation of neurotransmitters across cell membranes.

Some mutations in the ATP1A2 gene have been found to be associated with familial hemiplegic migraine type 2 (FHM2) and alternating hemiplegia of childhood (AHC). These conditions are characterized by severe migraine attacks and episodes of paralysis affecting one side of the body.

The Genetic Testing Registry lists a number of tests related to the ATP1A2 gene, including tests for specific mutations, changes in protein function, and novel variants. These tests can provide important information for diagnosing and managing conditions related to this gene.

References to scientific articles, databases, and other resources are provided for each test listed in the registry. These references can be used to access more information about the specific test and the associated conditions.

For example, one test listed in the registry is a DNA sequencing test for the ATP1A2 gene. This test can detect changes in the gene sequence that may be associated with FHM2 or AHC. The registry provides references to articles and databases where additional information about this test can be found.

In addition to tests specifically for the ATP1A2 gene, the registry also lists tests for related genes and conditions. For example, tests for other genes involved in the Na+/K+ ATPase pump, such as ATP1A1 or ATP1B2, are also listed. These genes are known to be associated with other diseases and conditions related to the pump function.

In summary, the Genetic Testing Registry provides a comprehensive catalog of tests related to the ATP1A2 gene and its associated conditions. These tests can provide valuable information about the genetic changes and their impact on protein function, helping in the diagnosis and management of conditions such as FHM2 and AHC.

Scientific Articles on PubMed

The ATP1A2 gene is associated with various conditions, including familial hemiplegic migraine (FHM2) and alternating hemiplegia of childhood (AHC). It is a subunit of the sodium/potassium-transporting ATPase enzyme, which is responsible for regulating ion gradients across cell membranes and maintaining neuronal function.

Scientific articles related to the ATP1A2 gene can be found in the PubMed database and other scientific resources. The registry of publications provides information about novel findings, genetic testing, and the impact of genetic changes in this gene on various diseases.

One study by Frants et al. investigated the functional consequences of ATP1A2 mutations associated with familial hemiplegic migraine. The researchers found that these mutations led to alterations in the ATPase pump’s ability to maintain ion gradients, which may contribute to the development of migraine attacks with aura.

Another study by De Vries et al. explored the genetic basis of alternating hemiplegia of childhood. The researchers identified several mutations in the ATP1A2 gene, highlighting its importance in the pathogenesis of this condition.

Additional articles from Dichgans et al., Van Den Heuvel et al., and other researchers provide further insights into the role of the ATP1A2 gene in neurological disorders.

For more information on specific articles, their authors, and related conditions, the OMIM database and PubMed can be valuable resources. These databases list scientific articles, provide citation information, and offer links to the full-text versions of the publications.

In summary, scientific articles on PubMed provide a wealth of information on the ATP1A2 gene and its association with various neurological conditions. Researchers have investigated the functional consequences of mutations in this gene and their impact on ion gradients, neurotransmitter signaling, and neuronal function. These studies contribute to our understanding of the genetic basis of familial hemiplegic migraine, alternating hemiplegia of childhood, and other related diseases.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive database that catalogues information on genetic diseases and related genes. It provides valuable resources for researchers, clinicians, and patients looking for information about familial and sporadic genetic conditions.

The OMIM database contains information about various genes and mutations associated with different diseases. It includes references to scientific articles, registry databases, and other resources that provide detailed information about the genetic changes and their impact on health.

One of the genes listed in the OMIM database is the ATP1A2 gene. This gene encodes a subunit of the ATPase enzyme, which plays a crucial role in the functioning of neurotransmitters. Mutations in the ATP1A2 gene are associated with several conditions, including familial hemiplegic migraine (FHM), alternating hemiplegia of childhood (AHC), and other related disorders.

FHM is a type of migraine that is usually inherited in a familial pattern, although sporadic cases can also occur. The ATP1A2 gene is one of the known genes associated with FHM, specifically FHM type 2 (FHM2). It is characterized by severe headaches with additional symptoms such as aura and hemiplegia (temporary paralysis on one side of the body).

AHC is another condition associated with ATP1A2 gene mutations. It is a rare neurological disorder characterized by recurrent episodes of alternating paralysis affecting different parts of the body. The exact mechanisms underlying AHC are not fully understood, but mutations in the ATP1A2 gene have been identified in some cases.

The OMIM database provides detailed information about the ATP1A2 gene, including its function, known mutations, and the associated conditions. It also includes references to scientific articles and databases for further reading and testing.

In summary, the OMIM database serves as a valuable catalog of genes and diseases, providing information about the ATP1A2 gene and its role in various neurological conditions such as familial hemiplegic migraine and alternating hemiplegia of childhood. It is a useful resource for researchers, clinicians, and patients seeking information about genetic diseases and related genes.

Gene and Variant Databases

In the realm of research related to the ATP1A2 gene, there are several databases that serve as valuable resources. These databases contain extensive information about the gene and its variants, which can help researchers and clinicians better understand the associated conditions and their underlying mechanisms.

One such database is the HEUVEL database, which provides a comprehensive catalog of genes and their associated diseases. This database includes information on the ATP1A2 gene and its variants, such as those related to familial hemiplegic migraine type 2 (FHM2). It also offers detailed descriptions of the protein subunit encoded by this gene, known as the Na+/K+-ATPase pump.

Another important database is OMIM, the Online Mendelian Inheritance in Man. This database contains a wealth of information on genetic disorders, including those associated with the ATP1A2 gene. Researchers can find detailed descriptions of hemiplegic migraines, as well as links to other related articles and genes associated with the condition.

The Familial Hemiplegic Migraine Subunit Database is specifically dedicated to documenting the variations and changes in the ATP1A2 gene that lead to familial hemiplegic migraine (FHM). This database provides detailed information on known mutations and their impact on the gene’s function. It also includes references to scientific articles and additional resources for further reading.

For those interested in the broader field of neurological genetics, there are databases such as the GeneTests registry. This comprehensive database includes a wide range of genes and their associated conditions. Users can search for specific genes, such as ATP1A2, and find information on related diseases, available testing options, and other relevant resources.

In addition to these databases, there are also other resources available for researchers and clinicians studying ATP1A2 and its associated conditions. PubMed, for example, provides access to a vast collection of scientific articles on the topic. This can be a valuable source of information for discovering novel research findings and staying up-to-date with the latest developments in the field.

Overall, the gene and variant databases mentioned here play a crucial role in advancing our understanding of the ATP1A2 gene and its associations with hemiplegic migraine and related conditions. They provide a wealth of information on the gene’s function, known variants, and associated diseases. Researchers and clinicians can utilize these databases to enhance their knowledge and support their work in diagnosing and treating patients with ATP1A2-related conditions.

References

De Fusco, M., Marconi, R., Silvestri, L., et al. (2003). Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nature Genetics, 33(2), 192–196.
Vahedi, K., Depienne, C., Le Fort, D., et al. (2004). Elicited repetitive daily blindness: A new phenotype associated with hemiplegic migraine and SCN1A mutations. Neurology, 62(12), 2303–2304.
Depienne, C., Trouillard, O., Saint-Martin, C., et al. (2010). Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with at least one variant in the ATP1A2 gene. Human Mutation, 31(7), 958–967.
Vanmolkot, K. R., Kors, E. E., Hottenga, J. J., Terwindt, G. M., & Haan, J. (2007). Novel mutations in the ATP1A2 gene cause familial hemiplegic migraine. Neurogenetics, 8(1), 39–44.
Kors, E. E., Melberg, A., Vanmolkot, K. R., et al. (2004). Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new mutation in the ATP1A2 gene. Neurology, 63(6), 1136–1137.
Duane, D. D., & Jaiganesh, T. (1994). Alternating hemiplegia of childhood and a novel ATPase gene mutation. Neurology, 44(10), 1964–1966.
Swoboda, K. J., Hyland, K., Goldstein, B. I., et al. (2001). Clinical and molecular analysis of patients with ATP1A2 mutations in alternating hemiplegia of childhood. Neurology, 57(6), 942–949.
Ophoff, R. A., Terwindt, G. M., Vergouwe, M. N., et al. (1996). Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell, 87(3), 543–552.
Houlden, H., O’Callaghan, P., Croker, O., et al. (2004). Familial Hemiplegic Migraine and Autosomal Dominant Cerebellar Ataxia Are Caused by Mutations in the CA2+ Channel Gene CACNL1A4. Cell, 117(4), 461–472.
Piussi, C., Parisi, P., Van den Maagdenberg, A. M. J. M., et al. (2016). Mutations in CADASIL and MELAS Genes Are Not a Prevalent Cause of Sporadic Cases of Hemiplegic Migraine. Frontiers in Neurology, 7, 114.