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DEPDC5 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

DEPDC5 gene

The DEPDC5 gene provides instructions for creating a protein essential to the GATOR1 complex, which regulates the mTOR signaling pathway involved in cell growth and brain development.

Normal Function

The DEPDC5 gene provides instructions for making a protein that is part of a larger group of proteins (a complex) called GATOR1. This complex is made up of the DEPDC5 protein and proteins made from two other genes: NPRL2 and NPRL3. GATOR1 is found in cells throughout the body, where it regulates a signaling pathway called the mTOR pathway. The mTOR pathway is involved in cell growth and division (proliferation) and the creation (synthesis) of new proteins. In the brain, the mTOR pathway regulates many processes, including the growth and development of nerve cells and their ability to change and adapt over time (plasticity).

The GATOR1 complex blocks this pathway by stopping (inhibiting) the activity of a complex called mTOR complex 1 (mTORC1) that is integral to the mTOR pathway.

Health Conditions Related to Genetic Changes

Autosomal dominant sleep-related hypermotor epilepsy

Pathogenic variants in the DEPDC5 gene can cause autosomal dominant sleep-related hypermotor epilepsy (ADSHE), a genetic form of epilepsy characterized by seizures that typically begin while a person is sleeping and involve some degree of muscle (motor) activity. The seizures may include:

  • Repetitive, abnormal muscle movements
  • Muscle stiffness
  • Abnormal body positioning

Pathogenic variants in the DEPDC5 gene lead to the production of an altered protein that disrupts the inhibitory function of the GATOR1 complex. This leads to an overactive mTOR signaling pathway that may cause the seizures in people with ADSHE.

Familial focal epilepsy with variable foci

Pathogenic variants in the DEPDC5 gene can also cause familial focal epilepsy with variable foci (FFEVF), an uncommon form of epilepsy that runs in families. Affected individuals experience focal seizures, which are seizures that begin in a specific region of the brain and may not affect consciousness. Some DEPDC5 gene variants cause cells to produce an abnormally short version of the protein that is quickly broken down. As a result, there is less functional DEPDC5 protein available to form the GATOR1 complex. Without enough functional GATOR1 complex, mTORC1 is not regulated properly and the mTOR pathway is abnormally active. Research suggests that increased mTOR pathway signaling in the brain changes the connections between nerve cells (synapses) and increases nerve cell activation (excitation), which can lead to seizures.

Autosomal dominant epilepsy with auditory features

MedlinePlus Genetics provides information about Autosomal dominant epilepsy with auditory features.

Other disorders

Pathogenic variants in the DEPDC5 gene are a rare cause of familial mesial temporal lobe epilepsy (FMTLE). Similar to individuals with FFEVF, people with FMTLE have focal seizures and may experience symptoms such as déjà vu, fear, or nausea before the seizure. As in FFEVF, most of the DEPDC5 gene variants that cause FMTLE reduce the amount of functional GATOR1 complex and cause the mTOR pathway to be abnormally active.

Pathogenic variants in the DEPDC5 gene can also cause infantile spasms, a type of seizure that usually appears before the age of 1 year and is characterized by repeated muscle contractions. The DEPDC5 gene variants that cause infantile spasms also reduce the amount of functional GATOR1 complex and increase the activity of the mTOR pathway.

Pathogenic variants in both copies of the DEPDC5 gene have been identified in some people with a form of developmental and epileptic encephalopathy (DEE). DEEs are a group of severe epileptic disorders characterized by developmental delays and abnormal brain function (encephalopathy) that worsens over time. Affected individuals often have seizures that are difficult to control with medication.

In some cases, people with seizures caused by a variant in DEPDC5 have experienced sudden unexpected death in epilepsy (SUDEP). SUDEP can occur in anyone with a seizure disorder, but it is more common in people with frequent or poorly controlled seizures.

It is currently unclear why individuals with variants in the same gene develop different seizure disorders.

Other Names for This Gene

  • DEE111
  • DEP domain containing 5
  • DEP.5
  • FFEVF
  • FFEVF1
  • FPEVF
  • KIAA0645

Frequently Asked Questions

Many individuals with DEPDC5-related epilepsy are resistant to standard anti-seizure medications, particularly those that target sodium channels. However, some patients have shown better responses to medications that modulate GABA or calcium channels. Because the underlying mechanism involves the mTOR pathway, researchers are investigating mTOR inhibitors as potential targeted therapies, though these are not yet standard clinical practice. Treatment plans are highly individualized and often require a multidisciplinary approach involving neurologists and geneticists.
The DEPDC5 protein helps regulate the mTOR pathway, which controls how brain cells grow and adapt. When this gene is mutated, the pathway becomes overactive, disrupting the normal electrical balance in the brain during sleep cycles. This hyperactivity makes the brain more susceptible to abnormal electrical discharges specifically when the body transitions into sleep, leading to the characteristic motor seizures seen in autosomal dominant sleep-related hypermotor epilepsy.
Early signs often appear in infancy or early childhood and include sudden, repetitive movements such as kicking, pedaling, or stiffening of the limbs that occur exclusively during sleep. Parents may initially mistake these for night terrors or restless sleep. However, unlike typical parasomnias, these episodes often involve complex, stereotyped motor patterns and may be followed by a period of confusion or unresponsiveness. A detailed family history and genetic testing are required to distinguish this from other sleep disorders.
Yes, autosomal dominant sleep-related hypermotor epilepsy caused by DEPDC5 variants is inherited in an autosomal dominant pattern. This means that only one copy of the altered gene is needed to cause the condition. If a parent has the mutation, there is a 50 percent chance with each pregnancy that the child will inherit the variant. Genetic counseling is recommended for families to understand inheritance risks and available testing options.
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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