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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CASS4
Cas scaffold protein family member 4
Chromosome 20 · 20q13.31
NCBI Gene: 57091Ensembl: ENSG00000087589.17HGNC: HGNC:15878UniProt: B4DII4
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of substrate adhesion-dependent cell spreadingcytoplasmfocal adhesionprotein tyrosine kinase bindingAlzheimer diseaselate-onset Alzheimers diseaseskull disordernon-small cell lung carcinoma
✦AI Summary

CASS4 (Cas scaffold protein family member 4) is a docking protein that functions as a scaffolding adapter in tyrosine kinase-based signaling pathways essential for cell adhesion, migration, and spreading 1. As the fourth member of the CAS protein family, CASS4 lacks enzymatic activity but contains specific recognition and binding sites for assembly of larger signaling complexes 1. The protein regulates focal adhesion kinase (FAK) activity and associates with FAK and SRC family kinases to activate downstream effectors that control the actin cytoskeleton 1. CASS4 promotes cell invasion through activation of the AKT signaling pathway, which leads to inhibition of E-cadherin expression and enhanced invasive capacity in non-small cell lung cancer cells 2. Disease relevance includes associations with Alzheimer's disease risk, where genome-wide association studies have identified CASS4 as one of the risk genes implicated in AD pathogenesis 34. The protein also shows involvement in immune system function and has been implicated in various pathological conditions including cancer, autoimmune disorders, and developmental diseases 1. Clinical significance extends to its role as a potential biomarker and therapeutic target, particularly given its involvement in cancer metastasis and neurodegeneration 5.

Sources cited
1
CASS4 is a scaffolding adapter protein that lacks enzymatic activity but contains specific recognition sites for signaling complex assembly
PMID: 26119091
2
CASS4 promotes cell invasion through AKT signaling pathway activation and E-cadherin inhibition
PMID: 27677288
3
CASS4 is identified as an Alzheimer's disease risk gene through genome-wide association studies
PMID: 33589840
4
CASS4 is among the newly discovered AD risk genes revealed by genomic analysis
PMID: 24951455
5
CAS proteins including CASS4 are important for cancer-associated signaling and various pathological conditions
PMID: 24962474
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.51Moderate
late-onset Alzheimers diseaseOpen Targets
0.31Weak
skull disorderOpen Targets
0.31Weak
non-small cell lung carcinomaOpen Targets
0.04Suggestive
alcohol drinkingOpen Targets
0.03Suggestive
myxosarcomaOpen Targets
0.03Suggestive
subarachnoid hemorrhageOpen Targets
0.02Suggestive
placenta praeviaOpen Targets
0.02Suggestive
crush injuryOpen Targets
0.02Suggestive
DysmetriaOpen Targets
0.02Suggestive
Abnormal pupillary functionOpen Targets
0.02Suggestive
placental retentionOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
SepsisOpen Targets
0.02Suggestive
lung cancerOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
psychiatric disorderOpen Targets
0.01Suggestive
LeishmaniasisOpen Targets
0.01Suggestive
peripheral arterial diseaseOpen Targets
0.01Suggestive
hypertrophic cardiomyopathyOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PICALMProtein interaction84%INPP5DProtein interaction81%SORL1Protein interaction81%ABCA7Protein interaction81%CELF1Protein interaction81%FERMT2Protein interaction81%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
35%
Liver
9%
Ovary
8%
Heart
7%
Brain
4%
Gene Interaction Network
Click a node to explore
CASS4PICALMINPP5DSORL1ABCA7CELF1FERMT2
PROTEIN STRUCTURE
Preparing viewer…
PDB2CRE · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.88Intermediate
Observed/Expected LoF0.37 [0.26–0.53]
RankingsWhere CASS4 stands among ~20K protein-coding genes
  • #13,855of 20,598
    Most Researched21
  • #3,322of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedCASS4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer's disease risk genes.
PMID: 33589840
Nat Genet · 2021
1.00
2
Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
PMID: 24951455
Biol Psychiatry · 2015
0.90
3
Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members.
PMID: 26119091
Gene · 2015
0.80
4
Genetics of Alzheimer's disease.
PMID: 25311924
Adv Genet · 2014
0.70
5
Cas proteins: dodgy scaffolding in breast cancer.
PMID: 25606587
Breast Cancer Res · 2014
0.60