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SERPINI1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SERPINI1 gene

The SERPINI1 gene provides instructions for producing neuroserpin, a protein essential for nervous system development, synaptic plasticity, and the regulation of chemical reactions in the brain.

Normal Function

The SERPINI1 gene provides instructions for making a protein called neuroserpin, which is a type of serine protease inhibitor (serpin). Serpins help control several kinds of chemical reactions by blocking (inhibiting) the activity of certain proteins. Neuroserpin inhibits the activity of an enzyme called tissue plasminogen activator (tPA), which plays a role in cell movement (migration), blood clotting, and inflammation.

By inhibiting tPA activity, neuroserpin is involved in the development and function of the nervous system. Neuroserpin helps nerve cells (neurons) divide and mature so they can take on specific functions (differentiation). Neuroserpin also plays a role in the development of synapses, which are the connections between neurons where cell-to-cell communication occurs. Synapses can change and adapt over time in response to experience, a characteristic called synaptic plasticity. Neuroserpin helps regulate synaptic plasticity, which suggests that it may be important for learning and memory.

Health Conditions Related to Genetic Changes

Familial encephalopathy with neuroserpin inclusion bodies

Variants (also called mutations) in the SERPINI1 gene have been found to cause familial encephalopathy with neuroserpin inclusion bodies (FENIB). This condition causes progressive dysfunction of the brain (encephalopathy), leading to a loss of intellectual functioning (dementia) and seizures. Affected individuals typically have seizures that involve sudden, involuntary muscle jerking or twitching (myoclonus).

Variants in the SERPINI1 gene can lead to single protein building blocks (amino acids) being substituted for others in the neuroserpin protein. These changes cause cells to produce abnormally shaped, unstable versions of neuroserpin. Within neurons, the altered neuroserpin proteins can attach to one another and form chains (neuroserpin polymers) that clump together to form neuroserpin inclusion bodies. These inclusion bodies occur in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The formation of neuroserpin polymers triggers a stress response in the endoplasmic reticulum that is communicated to other cell structures and ultimately leads to cell death. The gradual loss of neurons in certain parts of the brain causes progressive dementia and other features of FENIB.

Additionally, the formation of neuroserpin polymers likely results in the abnormal release of calcium ions from the endoplasmic reticulum into the cell. This can lead to certain neurons becoming more active than usual, which may trigger the abnormal brain activity that is associated with seizures in people with FENIB.

SERPINI1 gene variants also reduce or eliminate neuroserpin's ability to inhibit tPA in neurons. Researchers believe that unchecked tPA activity may also contribute to the signs and symptoms of FENIB.

Some SERPINI1 gene variants cause more severe forms of FENIB than others. Certain factors can influence the age at which FENIB symptoms appear and the severity of the disease:

  • How easily the abnormal neuroserpin protein forms neuroserpin polymers.
  • The number of inclusion bodies that form within neurons.

The easier it is for neuroserpin polymers to accumulate within neurons, the earlier the neurological problems appear and the more severe they are likely to be. Additionally, people with severe FENIB tend to have more widespread neuron loss than those with milder cases of FENIB.

Other Names for This Gene

  • Axonin-2
  • neuroserpin
  • NEUS_HUMAN
  • PI12
  • Protease inhibitor 12
  • Serpin I1

Frequently Asked Questions

FENIB typically begins in adulthood, often with subtle changes in cognitive function, such as memory problems or difficulty with executive functions. This progresses to a loss of intellectual functioning (dementia) and can include personality changes. A hallmark symptom is the development of seizures, particularly myoclonic seizures, which involve sudden, involuntary muscle jerking or twitching. The condition is progressive, meaning symptoms worsen over time, leading to increasing neurological decline.
Diagnosis of FENIB usually involves a combination of clinical evaluation of symptoms, neurological examination, and neuroimaging studies like MRI to look for brain changes. The definitive diagnosis is made through genetic testing, which identifies specific variants in the SERPINI1 gene. Sometimes, a brain biopsy may be performed to look for characteristic neuroserpin inclusion bodies within neurons, though genetic testing is less invasive and often sufficient.
FENIB is inherited in an autosomal dominant pattern, meaning only one copy of the altered SERPINI1 gene in each cell is sufficient to cause the disorder. If one parent has FENIB, there is a 50% chance with each pregnancy that their child will inherit the variant and develop the condition. Genetic counseling is highly recommended for affected individuals and their families to understand the inheritance pattern, discuss risks, and explore options for family planning.
Currently, there is no cure for FENIB, and treatments are primarily supportive, focusing on managing symptoms. Anti-epileptic medications can help control seizures. For dementia and cognitive decline, various therapies like occupational therapy, physical therapy, and speech therapy can help maintain function and quality of life for as long as possible. Regular monitoring and supportive care are essential.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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