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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCZ1
CCZ1 vacuolar protein trafficking and biogenesis associated
Chromosome 7 · 7p22.1
NCBI Gene: 51622Ensembl: ENSG00000122674.13HGNC: HGNC:21691UniProt: P86791
35PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activityprotein bindinglate endosomeMon1-Ccz1 complexneurodegenerative diseaseHypercholesterolemiaAlzheimer diseaseinfection
✦AI Summary

CCZ1 is a guanine nucleotide exchange factor (GEF) that functions as a critical component of the MON1-CCZ1 complex, regulating endosomal maturation through Rab5-to-Rab7 conversion 12. The complex catalyzes nucleotide exchange on RAB7A, enabling RAB7 activation on late endosomes and subsequent lysosomal fusion 2. Structurally, CCZ1 directly interacts with RAB7A's phosphate-binding loop, facilitating conformational changes essential for nucleotide exchange 2. CCZ1 mediates multiple cellular processes: early-to-late endosomal trafficking during filovirus infections (Marburg and Ebola), with nearly complete inhibition of viral replication upon CCZ1 disruption 3; apoptotic cell clearance through phagosome-lysosome fusion in intestinal macrophages 4; and lipid droplet catabolism via intermediate endosome formation 5. ESCRT-mediated cargo ubiquitination regulates CCZ1 recruitment timing during endosome maturation, with ubiquitinated proteins preventing RABX-5 displacement and delaying CCZ1-mediated Rab conversion 6. These functions position CCZ1 as a therapeutic target for filoviral infections and potentially inflammatory bowel disease, as impaired apoptotic clearance through CCZ1 dysfunction correlates with intestinal inflammation severity 34.

Sources cited
1
CCZ1 is essential for early-to-late endosomal trafficking of Marburg and Ebola viruses, and CCZ1 inhibition nearly completely abolishes these infections
PMID: 37880247
2
CCZ1 functions as part of MON1-CCZ1 complex to regulate RAB7 activation and phagosome-lysosome fusion required for apoptotic cell clearance
PMID: 32160108
3
CCZ1 knockdown accumulates intermediate endosomes and inhibits lipid droplet catabolism, indicating its role in endosomal trafficking and lipid homeostasis
PMID: 39994216
4
MON1-CCZ1 is a Rab7-specific GEF that mediates Rab5-to-Rab7 conversion during endolysosomal maturation
PMID: 34383013
5
Cryo-EM structure reveals CCZ1 directly interacts with RAB7A's phosphate-binding loop to facilitate nucleotide exchange
PMID: 40979223
6
ESCRT-driven cargo ubiquitination prevents RABX-5 displacement by CCZ1, regulating timing of Rab conversion during endosome maturation
PMID: 39910226
7
MON1/CCZ1 mediates Rab5-to-Rab7 conversion through the RABEX5-MON1/CCZ1 RabGEF cascade during endosome maturation
PMID: 40605338
8
CCZ1 is a member of HerMon family complexes functioning as Rab GEFs regulating vesicular trafficking
PMID: 31562761
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
HypercholesterolemiaOpen Targets
0.32Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
infectionOpen Targets
0.05Suggestive
skin squamous cell carcinomaOpen Targets
0.03Suggestive
type 1 diabetes mellitusOpen Targets
0.02Suggestive
Crohn's diseaseOpen Targets
0.02Suggestive
inflammatory bowel diseaseOpen Targets
0.02Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
Parkinson diseaseOpen Targets
0.01Suggestive
viral diseaseOpen Targets
0.01Suggestive
cervical squamous cell carcinomaOpen Targets
0.01Suggestive
Dravet syndromeOpen Targets
0.01Suggestive
glycogen storage disease VIOpen Targets
0.01Suggestive
major depressive disorderOpen Targets
0.01Suggestive
bacterial diseaseOpen Targets
0.01Suggestive
Ebola hemorrhagic feverOpen Targets
0.01Suggestive
Niemann-Pick diseaseOpen Targets
0.00Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
VPS11Protein interaction100%VPS16Protein interaction100%VPS33AProtein interaction100%RAB7AProtein interaction100%MON1BProtein interaction100%RMC1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
67%
Lung
58%
Ovary
52%
Liver
45%
Heart
18%
Gene Interaction Network
Click a node to explore
CCZ1VPS11VPS16VPS33ARAB7AMON1BRMC1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P86791
View on AlphaFold ↗
RankingsWhere CCZ1 stands among ~20K protein-coding genes
  • #10,932of 20,598
    Most Researched35
Genes detectedCCZ1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections.
PMID: 37880247
Nat Commun · 2023
1.00
2
PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation.
PMID: 32160108
Autophagy · 2021
0.90
3
Endosomal trafficking participates in lipid droplet catabolism to maintain lipid homeostasis.
PMID: 39994216
Nat Commun · 2025
0.80
4
ESCRTing the RABs through conversion.
PMID: 40605338
Biochem Soc Trans · 2025
0.70
5
Who's in control? Principles of Rab GTPase activation in endolysosomal membrane trafficking and beyond.
PMID: 34383013
J Cell Biol · 2021
0.60