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UNC13D gene

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

UNC13D gene

The UNC13D gene provides instructions for making a protein essential for immune system regulation and the destruction of targeted cells.

Normal Function

The UNC13D gene provides instructions for making a protein that is involved in the process of cell destruction (cytolysis) and the regulation of the immune system.

The UNC13D protein is involved in the release of substances from cells (exocytosis). In particular, it is important for the exocytosis of structures called cytolytic granules from immune cells called T cells and NK cells. These cells destroy other cells by secreting these granules, which contain cell-killing proteins, onto the membranes of target cells. The UNC13D protein helps transport these granules to the membrane, allowing cytolytic proteins to enter the cell and trigger it to self-destruct.

This mechanism also helps regulate the immune system by destroying unneeded T cells. Controlling the number of these cells prevents the overproduction of immune proteins called cytokines, which lead to inflammation and, in excess, cause tissue damage.

Health Conditions Related to Genetic Changes

Familial hemophagocytic lymphohistiocytosis

More than 50 UNC13D gene mutations have been identified in people with familial hemophagocytic lymphohistiocytosis. Most of these mutations alter the way the gene's instructions are pieced together, leading to a dysfunctional protein. The resulting shortage of functional UNC13D protein interferes with its role in cell destruction and immune regulation, leading to the exaggerated immune response characteristic of this condition.

Other disorders

A variant (polymorphism) of the UNC13D gene has been associated with a higher risk of a complication called macrophage activation syndrome in people with systemic juvenile idiopathic arthritis (SJIA). SJIA is an autoimmune disorder that causes persistent joint inflammation beginning in childhood. Macrophage activation syndrome is a life-threatening complication of SJIA with symptoms including:

  • Fever
  • Enlarged liver and spleen
  • Liver damage
  • Low numbers of blood cells

The UNC13D gene variant associated with this syndrome consists of a specific combination of individual changes in 12 DNA building blocks (nucleotides).

Other Names for This Gene

  • FHL3
  • HLH3
  • HPLH3
  • Munc13-4
  • UN13D_HUMAN

Frequently Asked Questions

The specific UNC13D gene variant (polymorphism) associated with macrophage activation syndrome (MAS) in SJIA is believed to impair the immune system's ability to properly clear activated immune cells. This can lead to an uncontrolled inflammatory response, triggering MAS, which is a severe and potentially life-threatening complication of SJIA.
Urgent signs of familial hemophagocytic lymphohistiocytosis (FHL) include persistent high fever, enlarged liver and spleen, skin rash, neurological changes like seizures or irritability, and unusual bleeding or bruising. Rapidly worsening symptoms or signs of infection in a child with a known UNC13D mutation should prompt immediate medical evaluation.
Treatment for FHL typically involves immunosuppressive therapy to control the exaggerated immune response, often using corticosteroids, chemotherapy, and specific immunomodulators. In many cases, a hematopoietic stem cell transplant (bone marrow transplant) is considered the only curative option, especially for severe or recurrent disease.
Familial hemophagocytic lymphohistiocytosis (FHL) caused by UNC13D mutations is inherited in an autosomal recessive pattern. This means a child must inherit two copies of the altered gene (one from each parent) to develop the condition. Parents are typically carriers and do not show symptoms, but there is a 25% chance with each pregnancy for them to have an affected child.
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.