Caspase Recruitment Domain Family Member 14

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Caspase Recruitment Domain Family Member 14

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Caspase Recruitment Domain Family Member 14</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CARD14</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q31.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>15292</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y2K7</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000100916</td>
</tr>
<tr>
<td class="label">Alias</td>
<td>CARMA2, bPS2</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">21 edges</a></td>
</tr>
</table>

Overview

...

Caspase Recruitment Domain Family Member 14

Overview

Mermaid diagram (expand to render)

Caspase Recruitment Domain Family Member 14 (CARD14) is a gene encoding a member of the CARD family of that play critical roles in regulating cell death, inflammation, and immune signaling pathways["@jordan2012"]. While CARD14 is most extensively studied in the context of inflammatory skin disorders such as psoriasis and psoriatic arthritis, emerging evidence suggests it may have important functions in the central nervous system and potentially in neurodegenerative [@mellett2015].

Gene Information

Protein Structure and Function

The CARD14 protein contains an N-terminal coiled-coil domain, a linker region, and a C-terminal CARD (Caspase Recruitment Domain) domain[@jordan2012]. This structure classifies it as a member of the CARMA (CARD-containing MAGUK protein) family, which function as scaffold in signaling pathways.

CARD14 is primarily expressed in skin keratinocytes and immune cells, but also shows expression in various tissues including the brain[@chang2018]. The protein serves as a scaffold for the assembly of signaling complexes that activate [NF-κB](/entities/nf-kb) and MAPK pathways, leading to the transcription of pro-inflammatory cytokines and mediators[@jiang2013].

Key Molecular Functions

NF-κB Activation: CARD14 recruits and activates key kinases (TAK1, IKKβ) that phosphorylate IκB, leading to NF-κB nuclear translocation and transcription of inflammatory genes[@jordan2012].

MAPK Signaling: Through interactions with TRAF , CARD14 activates both JNK and p38 MAPK pathways[@jiang2013].

Inflammasome Regulation: CARD14 can interact with caspase-1 and other inflammasome components to regulate IL-1β and IL-18 processing[@sahil2017].

Role in Neurodegeneration

While primarily studied in skin biology, CARD14 may contribute to neurodegenerative processes through several :

Neuroinflammation

Chronic neuroinflammation is a hallmark of [Alzheimer's disease](/diseases/alzheimers-disease) (AD), [Parkinson's disease](/diseases/parkinsons-disease) (PD), and amyotrophic lateral sclerosis (ALS)[@glass2010]. CARD14-mediated NF-κB activation in glial cells ([microglia](/cell-types/microglia-neuroinflammation) and astrocytes) could contribute to the persistent inflammatory environment observed in these disorders:

Alzheimer's Disease: Elevated NF-κB activity in AD brains drives expression of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) that promote amyloid-β production and [tau](/proteins/tau) pathology[@heneka2015]. CARD14 expression in microglia and [astrocytes](/entities/astrocytes) could be induced by amyloid-β plaques, creating a feed-forward inflammatory loop.
Parkinson's Disease: Neuroinflammation in PD is driven by activated microglia surrounding dopaminergic [neurons](/entities/neurons) in the substantia nigra[@hirsch2012]. CARD14-mediated inflammasome activation could contribute to IL-1β release and dopaminergic neuron death.
Amyotrophic Lateral Sclerosis: Motor neuron degeneration in ALS is accompanied by widespread neuroinflammation[@philips2015]. CARD14 expression in astrocytes and microglia may amplify inflammatory responses that accelerate motor neuron loss.

Blood-Brain Barrier Permeability

CARD14 expression in endothelial cells may influence [blood-brain barrier](/entities/blood-brain-barrier) (BBB) integrity[@daneman2015]. Dysregulated CARD14 signaling could increase BBB permeability, allowing peripheral immune cells and inflammatory mediators to enter the central nervous system.

Therapeutic Implications

Targeting CARD14 signaling may represent a novel therapeutic approach for neurodegenerative :

NF-κB Inhibitors: Small molecule inhibitors of NF-κB signaling could reduce neuroinflammation mediated by CARD14 pathway activation[@gilmore2013].
TAK1 Inhibitors: Since CARD14 signals through TAK1 to activate NF-κB, TAK1 inhibitors may provide a more targeted approach[@totzke2017].
Anti-inflammatory Cytokine Therapy: IL-1 receptor antagonists or IL-10 delivery could counteract CARD14-driven inflammation[@garlanda2019].

Disease Associations

[Alzheimer's Disease](/diseases/alzheimers-disease) Potent- [Parkinson's Disease](/diseases/parkinsons-disease)mation
[Parkinson's Disease](/diseases/parkinsons-disease) Inflammasome activation in dopaminergic degeneration
Amyotrophic Lateral Scl
[NCBI Gene](https:/- [UniProt](https://www.uniprot.org/)lm.nih.gov/gene/) inflammation co
[NCBI Gene](https:/- [UniProt](https://www.uniprot.org/)lm.nih.gov/gene/) External Links
[NCBI Gene](https:/- [UniProt](https://www.uniprot.org/)lm.nih.gov/gene/) CARD14
[UniProt](https://www.uniprot.org/) Q9Y2K7
Ensembl - ENSG00000100916

References

[Jordan MS, et al, CARD14 (2012)](https://pubmed.ncbi.nlm.nih.gov/22322037/)

[Mellett M, et al, CARD14 mutations in psoriasis (2015)](https://pubmed.ncbi.nlm.nih.gov/25167139/)

[Chang SH, et al, CARD14 expression in human tissues (2018)](https://pubmed.ncbi.nlm.nih.gov/29878647/)

[Jiang C, et al, CARD14-mediated NF-κB activation in keratinocytes (2013)](https://pubmed.ncbi.nlm.nih.gov/23913974/)

[Sahil S, et al, Inflammasome assembly and CARD14 (2017)](https://pubmed.ncbi.nlm.nih.gov/28452993/)

[Glass CK, et al, Mechanisms underlying neuroinflammation in neurodegenerative (2010)](https://pubmed.ncbi.nlm.nih.gov/20303880/)

[Heneka MT, et al, Neuroinflammation in Alzheimer's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25792098/)

[Hirsch EC, et al, Neuroinflammation in Parkinson's disease (2012)](https://pubmed.ncbi.nlm.nih.gov/22698779/)

[Philips T, et al, Neuroinflammation in ALS (2015)](https://pubmed.ncbi.nlm.nih.gov/26032768/)

[Daneman R, et al, The blood-brain barrier (2015)](https://pubmed.ncbi.nlm.nih.gov/26528756/)

[Gilmore TD, NF-κB inhibitors as therapeutic agents (2013)](https://pubmed.ncbi.nlm.nih.gov/24141804/)

[Totzke G, et al, TAK1 inhibitors (2017)](https://pubmed.ncbi.nlm.nih.gov/28052255/)

[Garlanda C, et al, IL-1 receptor antagonist therapy (2019)](https://pubmed.ncbi.nlm.nih.gov/31304786/)

Pathway Diagram

The following diagram shows the key molecular relationships involving Caspase Recruitment Domain Family Member 14 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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