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CARD14 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

CARD14 gene

The CARD14 gene provides instructions for making a protein that regulates inflammatory responses and is primarily found in the skin.

Normal Function

The CARD14 gene provides instructions for making a protein that turns on (activates) a group of interacting proteins known as nuclear factor-kappa-B (NF-κB). The NF-κB protein complex regulates the activity of multiple genes, including genes that control the body's immune responses and inflammatory reactions. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). The NF-κB protein complex also protects cells from certain signals that would otherwise cause them to self-destruct (undergo apoptosis).

The CARD14 protein is found in many of the body's tissues, but it is particularly abundant in the skin. NF-κB signaling appears to play important roles in regulating inflammatory reactions in the skin and in promoting the survival of skin cells.

Health Conditions Related to Genetic Changes

Generalized pustular psoriasis

At least three CARD14 gene mutations have been found in people with generalized pustular psoriasis (GPP), a rare and severe form of an inflammatory skin disorder called psoriasis. Individuals with GPP have repeated episodes in which large areas of skin become red and inflamed and develop small pus-filled blisters (pustules). The skin problems can be accompanied by fever and other signs of inflammation throughout the body (systemic inflammation). The episodes are thought to be triggered by infections, certain medications, pregnancy, or other stresses on the body. Most people with CARD14-associated GPP also have symptoms of the most common form of psoriasis called psoriasis vulgaris (PV), which is characterized by red, scaly patches of skin (plaques).

The CARD14 gene mutations associated with GPP (including GPP with PV) lead to production of an altered CARD14 protein that more readily turns on NF-κB. Overactive NF-κB signaling increases the activity of genes involved in the body's inflammatory response. The resulting abnormal inflammation contributes to the skin problems characteristic of GPP and PV.

CARD14 gene mutations increase the risk of developing GPP. Not everyone with a mutation in this gene has the characteristic problems with inflammation. This complex condition is thought to arise from a combination of genetic and environmental factors.

Familial pityriasis rubra pilaris

At least three mutations in the CARD14 gene have been identified in people with familial pityriasis rubra pilaris, a rare hereditary skin condition characterized by a patchy, salmon-colored skin rash covered in fine scales. These mutations lead to overactivation of NF-κB signaling, which triggers an abnormal inflammatory response in the skin.

Psoriatic arthritis

MedlinePlus Genetics provides information about Psoriatic arthritis.

Other disorders

Changes in the CARD14 gene may also contribute to other forms of psoriasis. At least two mutations have been identified in families with psoriasis. Several other rare variants of the CARD14 gene have been associated with an increased risk of psoriasis in people without a family history of the disorder. Studies suggest that these genetic changes enhance activation of NF-κB, resulting in abnormal inflammation, which is a characteristic feature of psoriasis. However, CARD14 gene mutations appear to be an uncommon risk factor for this condition.

Other Names for This Gene

  • bcl10-interacting maguk protein 2
  • BIMP2
  • CAR14_HUMAN
  • CARD-containing MAGUK protein 2
  • card-maguk protein 2
  • carma 2
  • CARMA2
  • caspase recruitment domain family, member 14
  • caspase recruitment domain-containing protein 14

Frequently Asked Questions

The CARD14 protein normally helps regulate the NF-κB signaling pathway, which controls inflammation and cell survival in the skin. When specific mutations occur in the CARD14 gene, the protein can become overactive or fail to properly shut down inflammatory signals. This leads to an exaggerated immune response where skin cells produce excessive inflammatory chemicals and fail to die off normally, resulting in the rapid formation of pus-filled blisters and widespread redness characteristic of generalized pustular psoriasis.
While the genetic mutation provides the underlying susceptibility, flares are usually triggered by external stressors on the immune system. Common triggers include bacterial or viral infections, such as strep throat or the common cold, which can activate the immune system and exacerbate the dysregulated NF-κB signaling. Other frequent triggers include the withdrawal of systemic corticosteroids, certain medications like lithium or antimalarials, physical trauma to the skin, and significant emotional or physical stress.
Generalized pustular psoriasis associated with CARD14 mutations is typically inherited in an autosomal dominant pattern, meaning only one copy of the altered gene is needed to cause the condition. If one parent has a CARD14 mutation, there is a 50 percent chance of passing the gene to each child. However, the condition often shows variable expressivity, meaning that even with the same genetic mutation, family members may experience different severities of symptoms or different types of psoriasis, such as having only mild plaque psoriasis versus severe generalized pustular episodes.
Diagnosis is confirmed through genetic testing that sequences the CARD14 gene to identify specific pathogenic variants. While the genetic test confirms the underlying cause, the immediate treatment for acute flares remains similar to other forms of severe psoriasis, often requiring systemic medications like biologics or immunosuppressants to control the inflammation. However, knowing the genetic status can be valuable for genetic counseling, helping patients understand the risk to family members and potentially guiding long-term management strategies to avoid known triggers more aggressively.
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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