Affinage

CARD14

Caspase recruitment domain-containing protein 14 · UniProt Q9BXL6

Length
1004 aa
Mass
113.3 kDa
Annotated
2026-04-28
73 papers in source corpus 23 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CARD14 is a CARD/MAGUK scaffold protein that nucleates a CBM (CARD14–BCL10–MALT1) signalosome in keratinocytes and other epithelial cells to activate NF-κB, MAPK (p38, JNK, ERK), and mTORC1 pathways, thereby controlling inflammatory gene expression, cell proliferation, and tissue homeostasis (PMID:11278692, PMID:27071417, PMID:39145956). The coiled-coil/linker region maintains autoinhibition; gain-of-function mutations that disrupt this region cause constitutive BCL10–MALT1 recruitment, MALT1 paracaspase activation, and upregulation of psoriasis-associated chemokines (CCL20, IL-8), while loss-of-function mutations dominantly suppress NF-κB and are linked to severe atopic dermatitis (PMID:22521418, PMID:27071417, PMID:30248356). In vivo, keratinocyte-intrinsic gain-of-function CARD14 signaling through MALT1 drives IL-23/IL-17A–dependent psoriatic inflammation that is ameliorated by MALT1 inhibition, TNF blockade, or IL-23 neutralization, and CARD14 also mediates IL-17A signaling via the ACT1–TRAF6 complex and TLR3 signaling via a TANK-containing complex (PMID:29980436, PMID:32343482, PMID:29689250, PMID:31486084). Gain-of-function CARD14 mutations cause familial psoriasis and pityriasis rubra pilaris (PMID:22521418, PMID:22703878).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Establishing that CARD14 is a CARD/MAGUK scaffold that directly engages BCL10 via CARD–CARD interaction to activate NF-κB answered the fundamental question of how this protein initiates signaling.

    Evidence Co-immunoprecipitation and NF-κB reporter assays with domain-mapping in transfected cells

    PMID:11278692

    Open questions at the time
    • Endogenous upstream stimuli unknown
    • No in vivo validation
    • Role of other MAGUK domains (PDZ, SH3, GUK) in signaling uncharacterized
  2. 2011 Medium

    Discovery of alternative splice isoforms (CARMA2sh and CARMA2cardless) with distinct domain compositions revealed that CARD14 can signal through TRAF2 in addition to BCL10, broadening its signaling repertoire.

    Evidence RT-PCR, co-immunoprecipitation, fluorescence microscopy, and apoptosis assays

    PMID:21302310

    Open questions at the time
    • TRAF2-dependent pathway not validated in primary cells
    • Relative isoform abundance in tissues unknown
    • Anti-apoptotic mechanism not delineated
  3. 2012 High

    Identification of gain-of-function CARD14 mutations (G117S, E138A) as causes of familial psoriasis and pityriasis rubra pilaris established CARD14 as a disease gene and linked NF-κB hyperactivation in keratinocytes to psoriatic pathology.

    Evidence Linkage analysis, exome sequencing, NF-κB reporter assays, transcriptome profiling, and immunohistochemistry in patient skin

    PMID:22521418 PMID:22521419 PMID:22703878

    Open questions at the time
    • Mechanism of autoinhibition disruption not yet defined
    • In vivo animal models not available
    • Downstream effector cytokine axis unknown
  4. 2016 High

    Demonstrating that psoriasis-associated mutations disrupt linker-mediated autoinhibition, constitutively recruit BCL10 and MALT1, and activate MALT1 paracaspase activity answered how gain-of-function mutations mechanistically drive inflammation and identified MALT1 as a druggable node.

    Evidence Co-immunoprecipitation, MALT1 enzymatic activity assays, MAPK phosphorylation, linker mutagenesis, and pharmacological MALT1 inhibition (mepazine) in primary keratinocytes

    PMID:27071417 PMID:27113748

    Open questions at the time
    • Structural basis of autoinhibition not resolved at atomic level
    • Relative contribution of MALT1 protease vs. scaffold function unclear
    • No in vivo validation yet
  5. 2017 High

    Card14 knockout mice revealed that CARD14 is essential for experimental psoriasis and acts downstream of IL-23 in hematopoietic cells controlling dermal γδ T cell IL-17 production, resolving the question of whether CARD14 functions cell-autonomously only in keratinocytes.

    Evidence Card14-/- mice, imiquimod and IL-23 injection models, bone marrow chimeras

    PMID:29150564

    Open questions at the time
    • Molecular mechanism in hematopoietic cells not defined
    • Relationship between keratinocyte-intrinsic and hematopoietic CARD14 functions unresolved
  6. 2018 High

    Card14 gain-of-function knock-in mice developed spontaneous IL-23/IL-17A–dependent psoriasis, and CARD14 was shown to mediate IL-17A signaling through association with the ACT1–TRAF6 complex, integrating CARD14 into the IL-17 receptor signaling pathway.

    Evidence Card14 knock-in and knockout mice, co-immunoprecipitation of CARD14 with ACT1–TRAF6, NF-κB/MAPK assays, cytokine neutralization (anti-IL-23p19)

    PMID:29689250 PMID:29980436

    Open questions at the time
    • How CARD14 is recruited to the IL-17R complex unclear
    • Whether CARD14 functions in IL-17 signaling in non-skin tissues not tested
  7. 2018 Medium

    Loss-of-function CARD14 mutations acting as dominant negatives on NF-κB in keratinocytes were linked to severe atopic dermatitis, revealing that CARD14 signaling dosage bidirectionally determines skin inflammatory phenotype.

    Evidence Dual luciferase reporter assay, immunohistochemistry in patient skin, exome sequencing

    PMID:30248356

    Open questions at the time
    • Animal model of loss-of-function alleles not generated
    • Mechanism of dominant-negative effect not molecularly defined
  8. 2019 Medium

    Identifying a CARMA2sh–TANK–MALT1 complex that mediates TLR3-induced NF-κB activation while CARMA2sh simultaneously represses TBK1/IRF3 revealed a dual signaling role downstream of innate immune receptors.

    Evidence Co-immunoprecipitation, siRNA knockdown, NF-κB reporter and IRF3 phosphorylation assays in keratinocyte cell line

    PMID:31486084

    Open questions at the time
    • In vivo relevance of TLR3–CARD14 axis not tested
    • Whether TBK1 repression is direct or indirect unknown
    • Psoriasis mutant TANK-binding defect not validated in primary cells
  9. 2020 High

    Keratinocyte-specific inducible CARD14E138A expression and conditional MALT1 deletion proved that keratinocyte-intrinsic CARD14–MALT1 signaling is sufficient and necessary for psoriatic inflammation, and that this axis is independent of adaptive immunity but dependent on TNF.

    Evidence Tamoxifen-inducible keratinocyte-specific transgenic mice, conditional MALT1 KO, MALT1 protease inhibitor, adaptive immune cell depletion, TNF blockade

    PMID:32343482 PMID:32597759

    Open questions at the time
    • Identity of TNF-producing cell type not established
    • Whether innate lymphoid cells contribute not tested
  10. 2020 Medium

    Identification of negative regulators RNF7, UBAC1/KPC, A20, and ABIN1 that modulate CARD14 signaling through ubiquitination of MALT1, NEMO, and TANK defined a regulatory layer controlling CARD14 signalosome output.

    Evidence Yeast two-hybrid, co-immunoprecipitation, ubiquitination assays (K63-linkage), NF-κB reporters

    PMID:29194363 PMID:33316896

    Open questions at the time
    • In vivo confirmation of negative regulator roles lacking
    • Whether these regulators are relevant in psoriasis patient tissue unknown
    • Relationship among multiple E3 ligases not tested
  11. 2021 Medium

    Finding that pathogenic CARD14 mutations increase replication stress–associated DNA double-strand breaks and promote break-induced replication revealed an unexpected role linking CARD14 signaling to genome maintenance and revertant mosaicism.

    Evidence γH2AX and comet assays, replication stress assays, sequencing of revertant patient skin patches

    PMID:34004138

    Open questions at the time
    • Mechanism connecting CARD14 NF-κB signaling to replication fork stress not defined
    • Whether effect is NF-κB-dependent or MALT1-dependent not tested
    • Generalizability beyond CARD14 mutations unknown
  12. 2024 High

    AP-MS–based interactome mapping revealed CARD14E138A associates with HOIP, TRAF6, AP2 adaptor complex, and PLK1, establishing that the active signalosome localizes to early endosomes via AP2, activates mTORC1 to drive keratinocyte proliferation, and is negatively regulated by PLK1.

    Evidence Affinity purification-mass spectrometry, co-immunoprecipitation, confocal/subcellular fractionation, mTORC1 activity assays, rapamycin treatment in mice, linker mutagenesis

    PMID:38797267 PMID:39145956

    Open questions at the time
    • Structural basis of endosomal targeting unknown
    • Whether mTORC1 activation occurs in WT CARD14 signaling not addressed
    • PLK1 regulatory mechanism (direct phosphorylation of CARD14?) not resolved
  13. 2025 Medium

    Intestinal epithelial CARD14E138A expression caused intestinal inflammation, reduced motility, Paneth cell dysfunction, and infection susceptibility, extending CARD14's physiological role beyond skin.

    Evidence IEC-specific transgenic mouse, histology, motility assay, transcriptomics, bacterial infection challenge

    PMID:41131424

    Open questions at the time
    • Whether endogenous intestinal CARD14 participates in homeostatic signaling unknown
    • Upstream stimuli activating CARD14 in IEC not defined
    • Relevance to human IBD not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological upstream signals that activate wild-type CARD14, the atomic-resolution structure of the autoinhibited and active signalosome, and the full extent of CARD14's roles beyond skin (gut, bone, vasculature) remain undefined.
  • No ligand or receptor that activates WT CARD14 identified
  • No crystal or cryo-EM structure of CARD14 or its signalosome
  • Relative contributions of keratinocyte-intrinsic vs. hematopoietic CARD14 in human psoriasis not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2 GO:0005768 endosome 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4
Partners
ACT1BCL10HOIPMALT1PLK1TANKTRAF2TRAF6
Complex memberships
ACT1-TRAF6 complexCARD14-TANK-MALT1 complexCBM signalosome (CARD14-BCL10-MALT1)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CARD14 is a CARD/MAGUK family scaffold protein whose CARD domain specifically associates with the CARD domain of BCL10, leading to NF-κB activation and BCL10 phosphorylation when expressed in cells. Co-immunoprecipitation, NF-κB reporter assay, domain mapping The Journal of biological chemistry High 11278692
2011 Alternative splicing of CARD14/CARMA2 generates two isoforms: CARMA2short (CARMA2sh, containing CARD, coiled-coil, and PDZ domains) and CARMA2cardless (lacking CARD domain). CARMA2sh localizes to the cytosol, interacts with TRAF2, activates NF-κB in a TRAF2-dependent manner, and protects cells from apoptosis. RT-PCR, fluorescence microscopy, co-immunoprecipitation, NF-κB reporter assay, apoptosis assay Journal of cellular physiology Medium 21302310
2012 Gain-of-function mutations in CARD14 (p.Gly117Ser, p.Glu138Ala) lead to enhanced NF-κB activation and upregulation of psoriasis-associated genes (CCL20, IL8) in keratinocytes compared to wild-type CARD14. CARD14 localizes mainly to basal and suprabasal layers of epidermis. NF-κB reporter assay, transfection in keratinocytes, transcriptome profiling, immunohistochemistry American journal of human genetics High 22521418 22521419
2012 CARD14 mutations causing familial pityriasis rubra pilaris increase CARD14 levels and activate NF-κB (p65) in affected skin, demonstrating CARD14's role as an activator of NF-κB signaling in epithelial inflammatory disease. Immunohistochemistry, NF-κB activation assay, linkage analysis and exome sequencing American journal of human genetics Medium 22703878
2014 CARD14 is expressed in dermal CD31+ endothelial cells in addition to epidermal keratinocytes. Transfection of dermal endothelial cells with psoriasis-associated CARD14 mutations results in increased expression of chemokines CXCL10, IL-8, and CCL2, with phosphorylated NF-κB detected in psoriatic CARD14+ CD31+ endothelial cells. Two-color immunofluorescence co-localization, transfection with mutant CARD14, chemokine quantification PloS one Medium 25369198
2014 DEPDC7 (DEP domain-containing protein) binds to CARMA2 (CARD14) and CARMA3 proteins. DEPDC7 displays cytosolic distribution, activates NF-κB when expressed, and shRNA-mediated knockdown impairs NF-κB activation downstream of G protein-coupled receptor stimulation that requires CARMA2. Yeast two-hybrid screening, co-immunoprecipitation, shRNA knockdown, NF-κB reporter assay PloS one Medium 25541973
2016 Psoriasis-associated CARD14 mutations (E138A and G117S) disrupt autoinhibition by the CARD14 linker region, causing constitutive interaction with BCL10 and MALT1, BCL10- and MALT1-dependent NF-κB activation in keratinocytes, MALT1 paracaspase activity stimulation, and ERK1/2 and p38α MAP kinase activation. MALT1 inhibition with mepazine reduces mutant CARD14-induced psoriasis-associated transcripts. Co-immunoprecipitation, NF-κB reporter assay, MALT1 activity assay, kinase phosphorylation assays, pharmacological inhibition, mutagenesis of linker region The Biochemical journal High 27071417
2016 CARD14 physically interacts with the paracaspase MALT1 and activates MALT1 proteolytic activity. CARD14 also activates p38 and JNK MAP kinase pathways in addition to NF-κB, all dependent on MALT1. Psoriasis-associated CARD14 mutations enhance MALT1 proteolytic activity and inflammatory gene expression. MALT1 deficiency or pharmacological inhibition of MALT1 catalytic activity inhibits mutant CARD14-induced cytokine/chemokine expression in primary human keratinocytes. Co-immunoprecipitation, MALT1 protease activity assay, genetic knockdown (MALT1 deficiency), pharmacological inhibition, gene expression analysis in primary keratinocytes EMBO reports High 27113748
2017 E3 ubiquitin ligase RNF7 interacts with CARMA2 (CARD14) and negatively regulates CARMA2's NF-κB-activating capacity by regulating the ubiquitination state of MALT1 and NEMO. Psoriasis-associated CARMA2sh mutants escape RNF7-mediated negative regulation. Yeast two-hybrid screening, co-immunoprecipitation, ubiquitination assay, NF-κB reporter assay International journal of molecular sciences Medium 29194363
2018 Card14 gain-of-function mutations (E138A and ΔQ136) in mice cause spontaneous psoriasis-like skin inflammation through constitutively activated CARMA2 self-aggregation, leading to enhanced IL-23–IL-17A cytokine axis activation. CARMA2 associates with the ACT1-TRAF6 signaling complex and mediates IL-17A-induced NF-κB and MAPK signaling in keratinocytes, driving pro-inflammatory gene expression. Card14-/- mice show attenuated imiquimod-induced skin inflammation due to impaired IL-17A signaling. Knock-in mouse models, Card14 knockout, co-immunoprecipitation (CARMA2 with ACT1-TRAF6), NF-κB and MAPK signaling assays, cytokine analysis, imiquimod psoriasis model Immunity High 29980436
2018 Heterozygous Card14ΔE138 gain-of-function mutation in mice is sufficient to spontaneously drive psoriatic skin disease via the IL-23/IL-17 axis. Neutralization of IL-23p19 significantly reduces skin lesions and proinflammatory cytokine expression, establishing IL-23 as a key downstream mediator of CARD14-driven inflammation. Knock-in mouse model, cytokine neutralization (anti-IL-23p19), histology, gene expression analysis The Journal of investigative dermatology High 29689250
2018 Loss-of-function mutations in CARD14 exert a dominant negative effect on NF-κB signaling in keratinocytes, demonstrated by dual luciferase reporter assay, and are associated with severe atopic dermatitis, with decreased CARD14 expression and decreased activated p65 levels in patient skin. Dual luciferase reporter assay, immunohistochemistry for p65, functional assays in keratinocytes, exome sequencing The Journal of allergy and clinical immunology Medium 30248356
2019 CARMA2sh forms a complex with TANK and MALT1 in keratinocytes. Both CARMA2sh and TANK are individually required for NF-κB activation following TLR3 stimulation (poly I:C). TANK is essential for TBK1/IRF3 pathway activation after poly I:C stimulation, whereas CARMA2sh functions as a repressor of this pathway. Psoriasis-associated CARMA2sh mutants bind TANK less efficiently and are less effective at suppressing the TBK1/IRF3 pathway. Co-immunoprecipitation, siRNA knockdown, NF-κB reporter assay, IRF3 phosphorylation assay in human keratinocyte cell line Journal of cellular physiology Medium 31486084
2020 CARD14E138A-induced skin inflammation and systemic disease in knock-in mice are independent of adaptive immune cells, ameliorated by blocking TNF, and induced specifically by CARD14E138A signaling in keratinocytes. Homozygous expression induces severe systemic disease resembling GPP acute exacerbations. Tamoxifen-inducible keratinocyte-specific knock-in mouse, adaptive immune cell depletion/absence, TNF blockade, bone marrow transplant eLife High 32597759
2020 Keratinocyte-specific inducible expression of CARD14E138A rapidly induces psoriatic skin inflammation and gene expression changes. Keratinocyte-specific MALT1 deletion and oral MALT1 protease inhibitor treatment both strongly reduce psoriatic skin disease, demonstrating a keratinocyte-intrinsic causal role for CARD14/MALT1 signaling in psoriasis. Inducible keratinocyte-specific transgenic mouse, conditional MALT1 KO, pharmacological MALT1 inhibition, histology, gene expression EMBO reports High 32343482
2020 UBAC1 (non-catalytic subunit of E3 ubiquitin ligase KPC complex) interacts with CARMA2sh and participates in the CARMA2sh/TANK complex, promoting K63-linked ubiquitination of TANK and negatively regulating the NF-κB-activating capacity of CARMA2sh following TLR3 stimulation in human keratinocytes. Yeast two-hybrid screening, co-immunoprecipitation, ubiquitination assay (K63-linkage), NF-κB reporter assay in keratinocytes International journal of molecular sciences Medium 33316896
2021 Pathogenic CARD14 mutations increase DNA double-strand breaks under conditions of replication stress (without affecting response to exogenous DNA damage stimuli), suppress new origin firings, and promote break-induced replication (BIR) via homologous recombination, leading to revertant mosaicism in patient skin. DNA damage assays (γH2AX, comet assay), replication stress assays, sequencing of revertant skin patches, X-irradiation and etoposide treatment comparisons American journal of human genetics Medium 34004138
2024 CARD14E138A associates with BCL10, MALT1, M1-ubiquitin E3 ligase HOIP, and K63-ubiquitin E3 ligase TRAF6; HOIP and TRAF6 interactions promote BCL10 ubiquitination and are essential for NF-κB and MAP kinase activation. Ubiquitin-binding proteins A20 and ABIN1 negatively regulate signaling by inducing CARD14E138A turnover. CARD14E138A localizes to early endosomes via association with the AP2 adaptor complex, and AP2 function is required for CARD14E138A activation of mTORC1, which stimulates keratinocyte metabolism and proliferation. Rapamycin (mTORC1 inhibitor) reduces CARD14E138A-induced keratinocyte proliferation and epidermal acanthosis in mice. Affinity purification-mass spectrometry, co-immunoprecipitation, subcellular fractionation/confocal imaging, mutagenesis, NF-κB reporter assay, mTORC1 activity assay, rapamycin treatment in mice The Biochemical journal High 39145956
2024 PLK1 (polo-like kinase 1) is a novel CARD14-binding protein identified by unbiased AP-MS. CARD14-PLK1 binding is independent of the CARD domain but involves a phospho-dependent PLK1-binding motif in the CARD14 linker region. Expression of CARD14E138A recruits PLK1 to CARD14-containing signalosomes in interphase keratinocytes. Disruption of the PLK1-binding motif in CARD14E138A increases CARD14-induced proinflammatory signaling and gene expression, indicating PLK1 is a negative regulator of CARD14 signaling. Affinity purification-mass spectrometry, co-immunoprecipitation, confocal imaging, linker region mutagenesis, gene expression analysis in keratinocytes Biochemical pharmacology Medium 38797267
2025 CARD14 expressed in intestinal epithelial cells (IEC) mediates NF-κB signaling. Mice expressing the gain-of-function CARD14E138A mutant specifically in IEC develop mild intestinal inflammation, drastically reduced intestinal motility (often with rectal prolapse), decreased Paneth cell antimicrobial peptide expression, microbial dysbiosis, and increased susceptibility to enteric bacterial infection. IEC-specific transgenic mouse model, histology, intestinal motility assay, transcriptome analysis of IEC, bacterial infection challenge EMBO molecular medicine Medium 41131424
2017 CARD14 is essential for murine experimental psoriasis (imiquimod and IL-23 models): Card14-/- mice show abrogated psoriasiform skin inflammation. Bone marrow chimera studies indicate CARD14 in radio-sensitive hematopoietic cells is required for IMQ-induced disease, controlling Vγ4+ T cells producing IL-17/IL-22 in the dermis/epidermis. CARD14 acts downstream of IL-23, not TLR7/TLR9. Card14 knockout mouse, imiquimod and IL-23 injection psoriasis models, bone marrow chimera, cell-type specific gene signature comparison Journal of immunology High 29150564
2026 CARD14 interacts with MYC and promotes osteoclast (OC) differentiation via a MYC-dependent pathway while simultaneously activating NF-κB and MAPK signaling. Adenoviral CARD14 overexpression in BM-derived macrophages increases OC differentiation/activity; BM-specific Card14 KO mice show reduced OC activity, improved trabecular bone microarchitecture, and increased bone mineral density. Co-immunoprecipitation (CARD14-MYC interaction), adenoviral overexpression, BM-specific conditional KO mouse, TRAP staining, micro-CT, histology, serum bone biomarkers Journal of bone and mineral research Medium 40971787

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 PSORS2 is due to mutations in CARD14. American journal of human genetics 320 22521418
2001 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. The Journal of biological chemistry 295 11278692
2012 Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. American journal of human genetics 284 22521419
2012 Familial pityriasis rubra pilaris is caused by mutations in CARD14. American journal of human genetics 192 22703878
2018 Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A. Immunity 132 29980436
2018 CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris. Journal of the American Academy of Dermatology 95 29477734
2015 Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris. The Journal of investigative dermatology 89 26203641
2014 The genetic background of generalized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants. Journal of dermatological science 88 24656634
2018 CARD14 Gain-of-Function Mutation Alone Is Sufficient to Drive IL-23/IL-17-Mediated Psoriasiform Skin Inflammation In Vivo. The Journal of investigative dermatology 80 29689250
2018 Clinical and Genetic Heterogeneity of CARD14 Mutations in Psoriatic Skin Disease. Frontiers in immunology 62 30386326
2017 Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by CARD14 Mutations. JAMA dermatology 62 27760266
2011 Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF-κB activation and endoplasmic reticulum stress-induced cell death. Journal of cellular physiology 62 21302310
2016 The paracaspase MALT1 mediates CARD14-induced signaling in keratinocytes. EMBO reports 61 27113748
2018 Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis. The Journal of allergy and clinical immunology 60 30248356
2016 Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation. The Biochemical journal 55 27071417
2014 CARD14 expression in dermal endothelial cells in psoriasis. PloS one 46 25369198
2018 CARD14/CARMA2 Signaling and its Role in Inflammatory Skin Disorders. Frontiers in immunology 37 30319628
2017 Beneficial effect of ustekinumab in familial pityriasis rubra pilaris with a new missense mutation in CARD14. The British journal of dermatology 34 28301045
2017 Essential Role of CARD14 in Murine Experimental Psoriasis. Journal of immunology (Baltimore, Md. : 1950) 32 29150564
2015 CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts. The British journal of dermatology 32 26358359
2016 CARD14-Mediated Activation of Paracaspase MALT1 in Keratinocytes: Implications for Psoriasis. The Journal of investigative dermatology 28 27939769
2019 Whole exome sequencing approach to childhood onset familial erythrodermic psoriasis unravels a novel mutation of CARD14 requiring unusual high doses of ustekinumab. Pediatric rheumatology online journal 27 31286971
2020 CARD14E138A signalling in keratinocytes induces TNF-dependent skin and systemic inflammation. eLife 25 32597759
2013 SNP rs11652075 in the CARD14 gene as a risk factor for psoriasis (PSORS2) in a Spanish cohort. DNA and cell biology 25 23905699
2018 Caspase recruitment domain (CARD) family (CARD9, CARD10, CARD11, CARD14 and CARD15) are increased during active inflammation in patients with inflammatory bowel disease. Journal of inflammation (London, England) 24 30008619
2016 Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis. The British journal of dermatology 22 26854129
2014 The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation. PloS one 21 25541973
2020 MALT1 targeting suppresses CARD14-induced psoriatic dermatitis in mice. EMBO reports 20 32343482
2005 Lack of evidence for genetic association to RUNX1 binding site at PSORS2 in different German psoriasis cohorts. The Journal of investigative dermatology 19 15654961
2006 Investigation of the chromosome 17q25 PSORS2 locus in atopic dermatitis. The Journal of investigative dermatology 18 16374479
2015 CARD14 gene polymorphism c.C2458T (p.Arg820Trp) is associated with clinical features of psoriasis vulgaris in a Chinese cohort. The Journal of dermatology 17 26249641
2020 Regulation and dysregulation of CARD14 signalling and its physiological consequences in inflammatory skin disease. Cellular immunology 16 32593012
2019 Histopathologic findings characteristic of CARD14-associated papulosquamous eruption. Journal of cutaneous pathology 16 31849081
2015 CARD14 Glu138 mutation in familial pityriasis rubra pilaris does not warrant differentiation from familial psoriasis. The Journal of dermatology 16 26130407
2017 The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling. International journal of molecular sciences 14 29194363
2016 Intra-familial Variation in Clinical Phenotype of CARD14-related Psoriasis. Acta dermato-venereologica 13 26984337
2020 UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex. International journal of molecular sciences 12 33316896
2016 The common CARD14 gene missense polymorphism rs11652075 (c.C2458T/p.Arg820Trp) is associated with psoriasis: a meta-analysis. Genetics and molecular research : GMR 12 27706581
2019 Gain of function p.E138A alteration in Card14 leads to psoriasiform skin inflammation and implicates genetic modifiers in disease severity. Experimental and molecular pathology 11 31323190
2023 Correlation of IL36RN and CARD14 mutations with clinical manifestations and laboratory findings in patients with generalised pustular psoriasis. Indian journal of dermatology, venereology and leprology 10 36331855
2015 Interaction of CARD14, SENP1 and VEGFA polymorphisms on susceptibility to high altitude polycythemia in the Han Chinese population at the Qinghai-Tibetan Plateau. Blood cells, molecules & diseases 10 26852650
2020 Two cases of CARD14-associated papulosquamous eruption from India. Pediatric dermatology 9 32323375
2016 Variants of CARD14 gene and psoriasis vulgaris in southern Chinese cohort. Anais brasileiros de dermatologia 9 26982778
2021 Altered replication stress response due to CARD14 mutations promotes recombination-induced revertant mosaicism. American journal of human genetics 8 34004138
2020 Knockdown of CARD14 Inhibits Cell Proliferation and Migration in Breast Cancer Cells. Anticancer research 8 32234884
2017 Acute generalized exanthematous pustulosis and polyarthritis associated with a novel CARD14 mutation. The Australasian journal of dermatology 8 28776328
2022 Association of PSORS1C3, CARD14 and TLR4 genotypes and haplotypes with psoriasis susceptibility. Genetics and molecular biology 7 36382932
2021 Identification of a pathogenic CARD14 mutation in a 70-year-old woman with pityriasis rubra pilaris: when genetic diagnosis influences choice of treatment strategy. BMJ case reports 7 33431438
2019 CARD14/CARMA2sh and TANK differentially regulate poly(I:C)-induced inflammatory reaction in keratinocytes. Journal of cellular physiology 7 31486084
2018 Nuclear Factor κB Activation in a Type V Pityriasis Rubra Pilaris Patient Harboring Multiple CARD14 Variants. Frontiers in immunology 7 30018619
2024 Case report: Successful treatment with biologics in a pediatric patient with a severe inflammatory skin disease and novel CARD14 mutation. Frontiers in medicine 6 38375322
2023 Case report: Infantile generalized pustular psoriasis with IL36RN and CARD14 gene mutations. Frontiers in genetics 6 36704338
2022 Association between CARD14 gene polymorphisms and psoriasis vulgaris in Hainan Han population based on exon sequencing: A case-control study. Medicine 6 36221432
2006 PSORS2 markers are not associated with psoriatic arthritis in the Italian population. Human heredity 6 16733365
2022 CARD14 Missense Variant Underlying CARD14-Associated Papulosquamous Eruption with Beneficial Response to Secukinumab. JID innovations : skin science from molecules to population health 5 36699196
2024 CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation. The Biochemical journal 3 39145956
2023 A novel mutation in a CARD14-associated papulosquamous eruption. Pediatric dermatology 3 36724903
2022 Association of CARD14 Single-Nucleotide Polymorphisms with Psoriasis. International journal of molecular sciences 3 36012602
2025 Similar Molecular Features in Two Cases of CARD14-Associated Papulosquamous Eruption. The Australasian journal of dermatology 2 40084598
2025 Clinical Characteristics of CARD14-Associated Papulosquamous Eruption and Evaluation of Therapeutic Efficacy of Secukinumab. Journal of inflammation research 2 40433052
2021 CARD14-associated papulosquamous eruption (CAPE) in a toddler responding to treatment with acitretin. Pediatric dermatology 2 34075616
2020 Updating and identifying three novel variants of the CARD14 gene in Chinese Han patients with psoriasis. Journal of genetics 2 33622988
2026 CARD14-mediated MYC interaction promotes osteoclastogenesis and bone density reduction in adolescent idiopathic scoliosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1 40971787
2025 Neonatal CARD14-Associated Papulosquamous Eruption: Response to Secukinumab During Infancy. Pediatric dermatology 1 40525499
2025 Case Report: Successful treatment of a novel variant of CARD14-mutated juvenile Pityriasis rubra pilaris with ixekizumab. Frontiers in medicine 1 40766060
2024 Polo-like kinase 1 (PLK1) is a novel CARD14-binding protein in keratinocytes. Biochemical pharmacology 1 38797267
2024 A case of revertant mosaic-like normal-looking spots in a patient with erythroderma with IL36RN and CARD14 heterozygous mutations. The Journal of dermatology 1 39373130
2023 Clinical features of acute generalized exanthematous pustulosis caused by hydroxychloroquine in rheumatology patients and exploration of CARD14 gene mutations. Frontiers in medicine 1 37089611
2022 Cutaneous and Developmental Effects of CARD14 Overexpression in Zebrafish. Biomedicines 1 36551948
2026 CARD14-Associated Papulosquamous Eruption (CAPE): An Updated Review of Pathogenesis and Treatment. International journal of dermatology 0 41845528
2025 Impact of CARD14 rs34367357 Mutation, Nutrition Status, and Seasonality on the Response to Biologic Therapy in Psoriasis-A Retrospective Observational Single-Center Study. Journal of clinical medicine 0 41010661
2025 CARD14 signaling in intestinal epithelial cells induces intestinal inflammation and intestinal transit delay. EMBO molecular medicine 0 41131424
2023 Acute generalized exanthematous pustulosis caused by hydroxychloroquine in a patient with rheumatoid arthritis and CARD14 mutation: Case report. Medicine 0 38013380