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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CCDC93
CCC complex scaffolding subunit CCDC93
Chromosome 2 · 2q14.1
NCBI Gene: 54520Ensembl: ENSG00000125633.12HGNC: HGNC:25611UniProt: Q567U6
55PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneGolgi to plasma membrane transportendocytic recyclingprotein-containing complexneurodegenerative diseaseintelligenceulcerative colitisDisorder of lipid metabolism
✦AI Summary

CCDC93 is a coiled-coil domain-containing protein that functions as a critical scaffolding subunit of the Commander complex, a 16-protein assembly essential for endosomal cargo recycling 1. CCDC93 works together with CCDC22 and COMMD proteins (COMMD1-10) to form the CCC complex, which couples with the Retriever subcomplex (VPS35L, VPS26C, VPS29) to coordinate SNX17-dependent recycling of over 120 cell surface proteins back from endosomes to the plasma membrane 2. This recycling machinery specifically recognizes transmembrane cargo containing ΦxNPxY/F motifs in their cytoplasmic domains 3. Clinically, CCDC93 mutations cause Ritscher-Schinzel syndrome (RSS), a congenital disorder characterized by cerebellar, cardiac, and craniofacial malformations, demonstrating that Commander complex dysfunction impairs tissue-specific surface protein presentation critical for development 3. Beyond RSS, Commander complex variants associate with Parkinson's disease risk through dysregulation of lysosomal homeostasis 4. Additionally, CCDC93 participates in LDL receptor trafficking and plasma lipid metabolism 5. The protein's evolutionary conservation extends to plants, where it regulates endosomal trafficking during root development 6.

Sources cited
1
CCDC93 is a subunit of the CCC complex within the Commander multiprotein assembly; forms coiled-coil structure connecting CCC and Retriever components
PMID: 37172566
2
CCDC93 couples with Retriever and WASH complexes to recycle over 120 cell surface proteins including integrins and receptors
PMID: 28892079
3
CCDC93 mutations cause Ritscher-Schinzel syndrome through disrupted Commander assembly and reduced surface recycling of proteins with specific sorting motifs
PMID: 40601774
4
Commander complex variants including CCDC93 modify lysosomal function and associate with Parkinson's disease risk
PMID: 40209002
5
CCDC93 complex involved in LDL receptor endosomal sorting and recycling
PMID: 28333714
6
CCDC93 homologue required for root and root hair growth in Arabidopsis, demonstrating evolutionary conservation
PMID: 36618652
7
CCDC93 scaffolds the Commander complex core and associates with cilium assembly and centrosome functions
PMID: 38459129
8
CCDC93 organizes structural organization of retriever-CCC complex; cancer-associated mutations disrupt complex formation
PMID: 38062209
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
intelligenceOpen Targets
0.43Moderate
ulcerative colitisOpen Targets
0.32Weak
Disorder of lipid metabolismOpen Targets
0.31Weak
Abnormality of the immune systemOpen Targets
0.25Weak
HypercholesterolemiaOpen Targets
0.19Weak
metabolic diseaseOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.07Suggestive
familial hypercholesterolemiaOpen Targets
0.07Suggestive
Varicose veinsOpen Targets
0.06Suggestive
vein disorderOpen Targets
0.05Suggestive
hyperlipidemiaOpen Targets
0.05Suggestive
hidradenitisOpen Targets
0.05Suggestive
Abnormality of the skeletal systemOpen Targets
0.05Suggestive
femoral neck fractureOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
muscular atrophyOpen Targets
0.05Suggestive
lymphatic system diseaseOpen Targets
0.04Suggestive
esophageal varicesOpen Targets
0.04Suggestive
response to statinOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
COMMD3Protein interaction100%WASHC1Protein interaction99%WASHC2CProtein interaction96%COMMD7Protein interaction87%WASHC4Protein interaction85%COMMD5Protein interaction81%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
95%
Ovary
62%
Lung
59%
Liver
34%
Brain
26%
Gene Interaction Network
Click a node to explore
CCDC93COMMD3WASHC1WASHC2CCOMMD7WASHC4COMMD5
PROTEIN STRUCTURE
Preparing viewer…
PDB8P0W · 2.90 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.99LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.66 [0.46–0.99]
RankingsWhere CCDC93 stands among ~20K protein-coding genes
  • #8,177of 20,598
    Most Researched55
  • #9,440of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedCCDC93
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
PMID: 37172566
Cell · 2023
1.00
2
Commander complex regulates lysosomal function and is implicated in Parkinson's disease risk.
PMID: 40209002
Science · 2025
0.90
3
Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling.
PMID: 28892079
Nat Cell Biol · 2017
0.80
4
Ritscher-Schinzel syndrome can be characterized as an endosomal recyclinopathy.
PMID: 40601774
Sci Transl Med · 2025
0.70
5
Structure and interactions of the endogenous human Commander complex.
PMID: 38459129
Nat Struct Mol Biol · 2024
0.60