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RAG2 gene

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

RAG2 gene

The RAG2 gene provides instructions for creating a protein complex essential for the immune system's ability to recognize and fight diverse foreign invaders.

Normal Function

The RAG2 gene provides instructions for making a member of a group of proteins called the RAG complex. This complex is active in immune system cells (lymphocytes) called B cells and T cells. These cells possess surface proteins that recognize foreign invaders; to recognize a wide variety of substances, these proteins must be diverse.

The genes for these proteins contain variable (V), diversity (D), and joining (J) segments. During protein production, these segments are rearranged in a process called V(D)J recombination. The RAG complex facilitates this by:

  • Attaching to a recombination signal sequence (RSS) located next to a V, D, or J segment.
  • Making small cuts in the DNA to allow segments to be separated and moved, creating various combinations.

Health Conditions Related to Genetic Changes

Omenn syndrome

More than 20 mutations in the RAG2 gene have been found to cause Omenn syndrome, a type of severe combined immunodeficiency (SCID). This condition is characterized by an almost total lack of immune protection and autoimmunity, where the immune system attacks the body's own tissues.

Mutations typically change single amino acids in the RAG2 protein, impairing the RAG complex's ability to bind to DNA. This diminishes V(D)J recombination, severely limiting the diversity of B and T cell surface proteins. While the number of T cells is typically normal, they are abnormal and attack the body's own cells, leading to the autoimmune features of the syndrome.

Other disorders

  • SCID: Mutations that completely eliminate RAG2 protein function cause a form of SCID associated with few or no B or T cells, leading to recurrent, fatal infections in infancy.
  • Immunodeficiency with granulomas: Mutations that result in a partially functional RAG2 protein lead to reduced numbers of B and T cells. Affected individuals may develop areas of inflammation called granulomas and typically do not develop severe infections until late childhood.

Other Names for This Gene

  • RAG-2
  • recombination activating gene 2
  • V(D)J recombination-activating protein 2

Frequently Asked Questions

Infants with Omenn syndrome or severe combined immunodeficiency (SCID) due to RAG2 mutations often present with recurrent, severe infections, including pneumonia, chronic diarrhea, and widespread skin rashes. They may also fail to thrive, meaning they don't gain weight or grow as expected. Omenn syndrome specifically can involve an enlarged liver and spleen, swollen lymph nodes, and an autoimmune-like rash.
Diagnosis typically involves blood tests to assess the number and function of B and T cells, which will show a severe lack of diverse immune cells. Genetic testing of the RAG2 gene is then performed to identify specific mutations. Newborn screening programs in many regions now include SCID, which can detect potential cases early through a T-cell receptor excision circle (TREC) test.
The primary curative treatment for both Omenn syndrome and SCID caused by RAG2 mutations is hematopoietic stem cell transplantation (HSCT), often referred to as a bone marrow transplant. This procedure replaces the faulty immune system with healthy stem cells. Supportive care includes infection prevention with antibiotics and antifungals, immunoglobulin replacement therapy, and nutritional support. Gene therapy is also an emerging treatment option.
Omenn syndrome and SCID caused by RAG2 mutations are typically inherited in an autosomal recessive pattern. This means both parents are usually carriers of one copy of the mutated RAG2 gene but do not show symptoms themselves. For each pregnancy, there is a 25% chance of having an affected child, a 50% chance of having a child who is a carrier, and a 25% chance of having a child who is neither affected nor a carrier. Genetic counseling is highly recommended for families.
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.