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NHLRC1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

NHLRC1 gene

The NHLRC1 gene provides instructions for making the protein malin, which acts as a quality control mechanism to degrade damaged proteins and regulate glycogen levels.

Normal Function

The NHLRC1 gene provides instructions for making a protein called malin. While active throughout the body, it plays a critical role in the survival of nerve cells (neurons) in the brain.

Malin is an E3 protein-ubiquitin ligase, part of the ubiquitin-proteasome system. This system tags damaged, misshapen, or excess proteins with a molecule called ubiquitin, signaling the cell to degrade them. This process regulates critical cell activities, including cell division and growth.

Malin also interacts with laforin (produced by the EPM2A gene) to regulate the production of glycogen. Researchers believe this interaction prevents the damaging buildup of glycogen in tissues that do not normally store it, such as the nervous system.

Health Conditions Related to Genetic Changes

Lafora progressive myoclonus epilepsy

More than 45 mutations in the NHLRC1 gene have been identified in people with Lafora progressive myoclonus epilepsy. These mutations typically prevent the production of malin or lead to a nonfunctional version of the protein.

  • Common Mutations: The most common mutation (Pro69Ala or P69A) is found in individuals of Portuguese, Italian, and Spanish heritage. Another common mutation (Gly158Ter or G158X) is seen across several ethnic groups.
  • Mechanism: Loss of malin prevents cells from regulating glycogen production. This leads to the formation of Lafora bodies—clumps of an abnormal form of glycogen called polyglucosan that cannot be broken down.
  • Neurological Impact: These clumps damage cells, with neurons being particularly vulnerable. The resulting death of neurons interferes with brain function, leading to seizures, movement abnormalities, and intellectual decline.

Other Names for This Gene

  • bA204B7.2
  • EPM2B
  • MALIN
  • MGC119262
  • MGC119264
  • MGC119265
  • NHL repeat containing 1
  • NHLC1_HUMAN

Frequently Asked Questions

Currently, there is no cure for Lafora progressive myoclonus epilepsy, and treatments focus on managing symptoms and improving quality of life. Anti-epileptic drugs (AEDs) are used to control seizures, though they often become less effective as the disease progresses. Other supportive therapies include physical therapy, occupational therapy, and speech therapy to address movement, coordination, and communication difficulties. Research is ongoing into therapies that might target the underlying glycogen accumulation.
Lafora progressive myoclonus epilepsy typically begins in late childhood or adolescence, often between ages 10 and 17. The earliest signs are usually seizures, which can be generalized tonic-clonic, absence, or myoclonic (sudden, brief muscle jerks). Other early symptoms may include visual disturbances (like seeing flashing lights or patterns), difficulties with coordination, subtle changes in personality or behavior, and a decline in school performance. These symptoms progressively worsen over time.
Diagnosis of Lafora progressive myoclonus epilepsy involves a combination of clinical evaluation, electroencephalogram (EEG) to detect characteristic brain activity patterns, and imaging studies like MRI to rule out other conditions. A definitive diagnosis often relies on genetic testing to identify mutations in the NHLRC1 gene (or EPM2A gene). In some cases, a skin or muscle biopsy may be performed to look for Lafora bodies, which are abnormal glycogen clumps, though genetic testing is now the preferred method.
Lafora progressive myoclonus epilepsy caused by NHLRC1 gene mutations is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated NHLRC1 gene, one from each parent, to develop the condition. If you have one mutated copy, you are a carrier and typically do not show symptoms. If both parents are carriers of an NHLRC1 mutation, there is a 25% chance with each pregnancy that their child will inherit two altered copies and develop Lafora disease, a 50% chance the child will be a carrier, and a 25% chance the child will not inherit any altered copies.
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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