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IFIH1 gene

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

IFIH1 gene

The IFIH1 gene provides instructions for making the MDA5 protein, a critical component of the innate immune system that helps the body detect and respond to viral infections.

Normal Function

The IFIH1 gene provides instructions for making the MDA5 protein, which plays an important role in innate immunity, the body's early response to foreign invaders (pathogens) such as viruses and bacteria. In particular, the MDA5 protein recognizes a molecule called double-stranded RNA. Certain viruses, including rhinovirus, respiratory syncytial virus (RSV), and the influenza (flu) virus, use RNA as their genetic material or produce RNA when they infect cells and replicate themselves.

MDA5 proteins attach themselves to pieces of viral RNA inside the cell, forming a filament. This stimulates signals that turn on the production of immune system proteins called interferons. Interferons control the activity of genes that help block viruses from replicating and stimulate the activity of certain immune system cells to fight infection. Interferons also help regulate inflammation, which is another part of the body's innate immune response.

Health Conditions Related to Genetic Changes

Aicardi-Goutières syndrome

Variants in the IFIH1 gene have been found to cause Aicardi-Goutières syndrome, a disorder characterized by abnormalities of the immune system, skin, and brain. These are "gain-of-function" variants that lead to an MDA5 protein that is more active than usual, causing the cell to produce excessive interferons and leading to inflammation. This constant inflammation is thought to damage brain and skin cells and create calcium deposits in the brain.

MDA5 deficiency

A few variants in the IFIH1 gene cause MDA5 deficiency, an immunodeficiency that leads to recurrent, severe viral infections in the respiratory tract. These "loss-of-function" variants result in an altered MDA5 protein that cannot function, preventing the immune system from mounting an effective early response to viruses.

Other disorders

IFIH1 gene variants have also been found to cause Singleton-Merten syndrome, which involves calcium deposits in the aorta and heart valves, tooth abnormalities, and low bone density. Like Aicardi-Goutières syndrome, this is caused by gain-of-function variants leading to excessive inflammation. Additionally, common variations (polymorphisms) in the IFIH1 gene have been associated with other autoimmune disorders.

Other Names for This Gene

  • IDDM19
  • interferon-induced helicase C domain-containing protein 1
  • MDA-5
  • MDA5
  • melanoma differentiation-associated gene 5
  • melanoma differentiation-associated protein 5
  • murabutide down-regulated protein
  • RIG-I-like receptor 2
  • RLR-2
  • RNA helicase-DEAD box protein 116

Frequently Asked Questions

Infants typically present in the first months of life with developmental stagnation or regression, unexplained irritability, recurrent sterile fevers, progressive microcephaly, and muscle stiffness or dystonia. A distinct clinical hallmark is the appearance of chilblain-like skin lesions, which are painful, purplish, inflammatory swellings primarily affecting the fingers, toes, and ears, especially in cooler weather.
Because the underlying issue is an overproduction of type I interferons (a type I interferonopathy), therapies focus on blocking this signaling cascade. Janus kinase (JAK) inhibitors, such as baricitinib or tofacitinib, are used to block downstream interferon receptor signaling. Clinical studies have shown that JAK inhibition can improve skin lesions, reduce systemic inflammation, and potentially stabilize neurological symptoms.
The clinical outcome depends entirely on the functional consequence of the mutation. "Gain-of-function" mutations lock the MDA5 protein into an hyperactive state, causing it to trigger chronic, inappropriate production of type I interferons without any viral trigger, resulting in neuroinflammatory conditions like Aicardi-Goutieres syndrome. Conversely, "loss-of-function" mutations disable MDA5, leaving cells unable to recognize viral double-stranded RNA and rendering the patient severely immunodeficient against ordinary respiratory viruses.
Individuals with loss-of-function variants lack critical innate defense against common respiratory RNA viruses like rhinovirus, respiratory syncytial virus (RSV), and influenza. Precautions include strict adherence to viral vaccination schedules (especially annual influenza immunization), aggressive infection-avoidance hygiene measures, rapid diagnostic viral panels during any acute febrile illness, and early consideration of antiviral medications or supplemental respiratory support to prevent life-threatening pneumonitis.
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.