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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CARD6
caspase recruitment domain family member 6
Chromosome 5 · 5p13.1
NCBI Gene: 84674Ensembl: ENSG00000132357.15HGNC: HGNC:16394UniProt: Q9BX69
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingregulation of apoptotic processcytoplasmalcohol drinkingesophageal squamous cell carcinomapsoriasiscolorectal carcinoma
✦AI Summary

CARD6 (caspase recruitment domain family member 6) is a multifunctional signaling protein primarily involved in regulating cell death, inflammation, and immune responses. As a CARD-containing protein, CARD6 interacts with RIP family kinases and associates with microtubules to modulate NF-κB activation 1, playing roles in both innate and adaptive immunity. CARD6 protects against hepatic ischemia/reperfusion injury by suppressing ASK1 phosphorylation and its downstream effectors JNK and p38, thereby reducing hepatocyte death and inflammation 2. In cardiac tissue, CARD6 serves as a cardioprotective factor by negatively regulating MEK kinase-1-dependent signaling, attenuating pathological hypertrophy in response to pressure overload 3. Emerging evidence demonstrates that circular CARD6 (circ-CARD6) acts as a competitive endogenous RNA, regulating oxidative stress-induced apoptosis and autophagy in retinal pigment epithelium through the miR-29b-3p/PRDX6/PI3K/Akt axis 4, and promoting posterior capsule opacification via the miR-31/FGF7 axis 5. Additionally, CARD6 is identified as a key biomarker in psoriasis and atherosclerosis pathogenesis, where it modulates immune cell activity and inflammatory responses 6. CARD6 is upregulated in gastrointestinal cancers including esophageal, gastric, and colorectal cancers, suggesting involvement in NF-κB-driven oncogenic pathways 7.

Sources cited
1
CARD6 protects against hepatic ischemia/reperfusion injury by suppressing ASK1 signaling and reducing hepatocyte death and inflammation
PMID: 29958938
2
CARD6 associates with microtubules, interacts with RICK kinase, and positively modulates NF-κB activation
PMID: 16418290
3
CARD6 is cardioprotective by negatively regulating MEK kinase-1-dependent MEK-ERK1/2 and JNK1/2 signaling in cardiac hypertrophy
PMID: 24777975
4
Circular CARD6 inhibits oxidative stress-induced apoptosis and autophagy in retinal pigment epithelium via the miR-29b-3p/PRDX6/PI3K/Akt axis
PMID: 37939831
5
Exosome-transmitted circ-CARD6 promotes posterior capsule opacification by sponging miR-31 to regulate FGF7 expression
PMID: 33844960
6
CARD6 is a key biomarker in psoriasis and atherosclerosis that modulates immune cell activity and inflammatory responses
PMID: 39072329
7
CARD6 protein is upregulated in esophageal, gastric, and colorectal cancer tissues and may activate NF-κB pathway in gastrointestinal cancers
PMID: 20025480
8
CARD6 is structurally unique among CARD proteins and potentially related to interferon-inducible GTPases with host defense functions
PMID: 16582588
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.02Suggestive
esophageal squamous cell carcinomaOpen Targets
0.02Suggestive
psoriasisOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
macular degenerationOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
Colon Sessile Serrated Adenoma/PolypOpen Targets
0.02Suggestive
Hepatic steatosisOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
cystic fibrosisOpen Targets
0.01Suggestive
Insulin resistanceOpen Targets
0.01Suggestive
lung carcinomaOpen Targets
0.01Suggestive
rheumatoid arthritisOpen Targets
0.01Suggestive
type 2 diabetes mellitusOpen Targets
0.01Suggestive
septic shockOpen Targets
0.01Suggestive
Ischemic strokeOpen Targets
0.01Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.01Suggestive
cardiac hypertrophyOpen Targets
0.01Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HS1BP3Shared pathway100%DCAF10Shared pathway100%BCL2L15Shared pathway100%RASSF6Shared pathway100%RIPK2Protein interaction100%NOD1Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Heart
44%
Liver
25%
Bone Marrow
18%
Ovary
17%
Brain
11%
Gene Interaction Network
Click a node to explore
CARD6HS1BP3DCAF10BCL2L15RASSF6RIPK2NOD1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BX69
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.49LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.05 [0.76–1.49]
RankingsWhere CARD6 stands among ~20K protein-coding genes
  • #15,507of 20,598
    Most Researched15
  • #15,096of 17,882
    Most Constrained (LOEUF)1.49
Genes detectedCARD6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Exploration of ferroptosis and necroptosis-related genes and potential molecular mechanisms in psoriasis and atherosclerosis.
PMID: 39072329
Front Immunol · 2024
1.00
2
Caspase recruitment domain 6 protects against hepatic ischemia/reperfusion injury by suppressing ASK1.
PMID: 29958938
J Hepatol · 2018
0.90
3
CARD tricks: controlling the interactions of CARD6 with RICK and microtubules.
PMID: 16582588
Cell Cycle · 2006
0.80
4
Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-kappaB activation.
PMID: 16418290
Proc Natl Acad Sci U S A · 2006
0.70
5
Circ-CARD6 inhibits oxidative stress-induced apoptosis and autophagy in ARPE-19 cells via the miR-29b-3p/PRDX6/PI3K/Akt axis.
PMID: 37939831
Exp Eye Res · 2024
0.60