CARD14 Gene
Synonym(s)
DefinitionThis section has been translated automatically.
The CARD14 gene (acronym for "caspase recruitment domain-containing protein 14" also known as "CARD-containing MAGUK protein 2 or Carma 2) is a protein-coding gene associated with psoriasis vulgaris, pustular psoriasis generalisata, as well as the autosomal dominant form of pityriasis rubra pilaris. The protein CARD14 encoded by this gene activates, among others, nuclear factor kappa B (NF-kappaB) and regulates a subset of psoriasis-associated genes in keratinocytes.
In humans, the CARD14 protein is encoded by the CARD14 gene, which is located on chromosome 17q25.3. The CARD14 protein belongs to the MAGUK - (membrane-associated guanylate kinase) family. Overexpression of CARD14 leads to activation of the transcription factor NF-κB and phosphorilation of BCL10.
General informationThis section has been translated automatically.
It is believed that mutations in the CARD14 gene, in combination with environmental factors, can trigger psoriasis. Thus, mutations in CARD14 are associated with psoriasis pustulosa generalisata . CARD14 activates, among others, nuclear factor kappa B (NF-kappaB) and regulates a subset of psoriasis-associated genes in keratinocytes.
CARD 14 mutations are associated with the atypical juvenile type of pityriasis rubra pilaris. This is characterized by occurrence limited to palms and soles; occasional familial occurrence.
CARD14 mutations have also been described in acrodermatitis chronica suppurativa.
The encoded CARD14 protein is detected in the basal and suprabasal layers of the healthy epidemis. In lesional psoriatic epidermis, it is reduced in the basal portions but upregulated in the suprabasal portions. Apparently, triggering (including local triggering as in the Köbner phenomenon) can cause a gain-of-function mutation in the CARD14 gene, which leads to local inflammation via a cascade of activation processes.
Clinical pictureThis section has been translated automatically.
CARD14-associated papulosquamous eruption (CAPE) is a rare autosomal dominant dermatosis that classically presents in early childhood (usually during the 1st year of life) with clinical features of both psoriasis and pityriasis rubra pilaris (PRP). The disease is known to be resistant to topical and systemic therapies classically used for psoriasis (Craiglow BG et al. 2018).Heterozygous gain-of-function mutations in CARD14 are observed in pityriasis rubra pilaris (PRP type V), which have not been found in other PRP types.
LiteratureThis section has been translated automatically.
- Bertin J et al. (2014) "CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B." J Biol Chem 276: 11877-1182.
- Craiglow BG et al. (2018 ) CARD14 - Associated Papulosquamous Eruption (CAPE): A Spectrum Including Features of Psoriasis and Pityriasis Rubra Pilaris. J Am Acad Dermatol. 2018 Sep; 79(3): 487-494.
- Howes, A et al. (2016) "Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation." The Biochemical journal. PMID 27071417.
- Jordan CTet al. (2012) Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. The American Journal of Human Genetics doi:10.1016/j.ajhg.2012.03.013.
- Jordan CTet al. (2012) PSORS2 is due to mutations in CARD14. The American Journal of Human Genetics 90: 784-795.
- Lwin SM et al2018) Benefi. (cial effect of ustekinumab in familial pityriasis rubra pilaris with a new
missense mutation in CARD14. Br J Dermatol 178:969-972.