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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CRACD
capping protein inhibiting regulator of actin dynamics
Chromosome 4 · 4q12
NCBI Gene: 57482Ensembl: ENSG00000109265.15HGNC: HGNC:29219UniProt: A0A2R8Y6P1
40PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of actin filament polymerizationprotein bindingnegative regulation of barbed-end actin filament cappingepithelial structure maintenanceesophageal diseaseresponse to selective serotonin reuptake inhibitorplacenta praeviapoisoning
✦AI Summary

CRACD (capping protein inhibiting regulator of actin dynamics) functions as a critical regulator of actin cytoskeleton dynamics with tumor suppressor properties. The protein promotes actin polymerization by inhibiting capping protein interactions with actin filaments, thereby maintaining epithelial cell integrity 1. CRACD stabilizes the cadherin-catenin-actin complex, and its loss disrupts this complex leading to β-catenin release and Wnt signaling hyperactivation 1. In cancer contexts, CRACD frequently shows reduced expression or mutations across multiple tumor types. CRACD loss drives neuroendocrine plasticity in lung cancers by disrupting actin organization, which suppresses Yap1-NOTCH signaling and promotes neuroendocrine gene expression 23. Additionally, CRACD inactivation leads to EZH2-mediated histone methylation and MHC-I gene repression, facilitating immune evasion 2. In colorectal cancer, decreased CRACD expression correlates with increased stemness, metastasis, and poor prognosis through YAP-mediated pathways 4. Paradoxically, some studies report CRAD as oncogenic in lung cancer, where knockdown suppresses growth and promotes apoptosis via Claudin 4 regulation 5. These findings establish CRACD as a multifunctional cytoskeletal regulator with complex, context-dependent roles in cancer biology.

Sources cited
1
CRACD stabilizes cadherin-catenin-actin complex and its loss leads to β-catenin release and Wnt signaling activation
PMID: 30361697
2
CRACD loss drives neuroendocrine plasticity and immune evasion in small cell lung cancer through actin disruption
PMID: 41353272
3
CRACD knockout induces neuroendocrine cell plasticity in lung adenocarcinoma
PMID: 38796854
4
CRACD negatively correlates with colorectal cancer progression, stemness, and metastasis via YAP-mediated pathways
PMID: 35172140
5
CRAD knockdown suppresses lung cancer cell growth and promotes apoptosis via Claudin 4 regulation
PMID: 33006362
Disease Associationsⓘ20
esophageal diseaseOpen Targets
0.36Weak
response to selective serotonin reuptake inhibitorOpen Targets
0.30Weak
placenta praeviaOpen Targets
0.27Weak
poisoningOpen Targets
0.26Weak
disorder of earOpen Targets
0.25Weak
auditory system diseaseOpen Targets
0.23Weak
adolescent idiopathic scoliosisOpen Targets
0.19Weak
hematologic diseaseOpen Targets
0.15Weak
attention deficit hyperactivity disorderOpen Targets
0.10Weak
neoplasmOpen Targets
0.10Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.09Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.09Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.09Suggestive
schizophrenia 15Open Targets
0.09Suggestive
small cell lung carcinomaOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.07Suggestive
movement disorderOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
autismOpen Targets
0.06Suggestive
Tourette syndromeOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MUC6Shared pathway33%MUC13Shared pathway33%PRRC1Shared pathway33%VSIG1Shared pathway25%TFF2Shared pathway25%TFF3Shared pathway25%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
24%
Heart
4%
Ovary
3%
Liver
1%
Lung
1%
Gene Interaction Network
Click a node to explore
CRACDMUC6MUC13PRRC1VSIG1TFF2TFF3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6ZU35
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.46–0.71]
RankingsWhere CRACD stands among ~20K protein-coding genes
  • #10,153of 20,598
    Most Researched40
  • #5,468of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedCRACD
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Actin dysregulation induces neuroendocrine plasticity and immune evasion: a vulnerability of small cell lung cancer.
PMID: 41353272
Nat Commun · 2025
1.00
2
CRACD loss induces neuroendocrine cell plasticity of lung adenocarcinoma.
PMID: 38796854
Cell Rep · 2024
0.90
3
PMID: 39201643
Int J Mol Sci · 2024
0.80
4
lncRNA Sequencing Reveals Neurodegeneration-Associated FUS Mutations Alter Transcriptional Landscape of iPS Cells That Persists in Motor Neurons.
PMID: 37887305
Cells · 2023
0.70
5
A Rare Case of Profound Pulmonary Venous Malformation in an Elderly Individual With Three Major Comorbidities: Genetic Insights.
PMID: 41234971
Cureus · 2025
0.60