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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CCDC66
coiled-coil domain containing 66
Chromosome 3 · 3p14.3
NCBI Gene: 285331Ensembl: ENSG00000180376.18HGNC: HGNC:27709UniProt: A2RUB6
40PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
centrosomespindleaxonememidbodymathematical abilitycrush injurysign or symptomChest pain
✦AI Summary

CCDC66 is a microtubule-associated protein with essential roles in ciliogenesis and cell division. Primary function involves regulating primary cilium assembly, length, and stability through microtubule stabilization 1. CCDC66 localizes dynamically to centrosomes, centriolar satellites, transition zones, and ciliary axonemes 2, mediating protein trafficking to these compartments 3. The protein cooperates with ciliopathy-linked factors CEP104 and CSPP1 to regulate transition zone assembly and IFT-B complex recruitment, controlling both cilium structure and Hedgehog signaling 2. During cell division, CCDC66 functions in mitotic progression by regulating spindle assembly, kinetochore-fiber integrity, and chromosome 3; and in cytokinesis through central spindle and midbody organization 4. This dual functionality involves microtubule nucleation via gamma-tubulin recruitment and microtubule bundling through its C-terminal domain 4. Disease relevance includes ciliopathies such as Joubert syndrome, where CCDC66 dysfunction causes shortened cilia with impaired axonemal modifications and aberrant ciliary stability 5. Additionally, circulating CCDC66 shows diagnostic potential as a colorectal cancer biomarker 6. These multifaceted roles establish CCDC66 as a critical regulator integrating ciliary and mitotic microtubule dynamics.

Sources cited
1
CCDC66 stabilizes microtubules and regulates cilium maintenance, disassembly, and epithelial organization via actin and vesicular trafficking
PMID: 40729374
2
CCDC66 regulates cilium length and assembly through interactions with transition zone and axonemal proteins, recruits IFT-B machinery, and cooperates with CEP104 and CSPP1
PMID: 36606424
3
CCDC66 is a microtubule-associated protein that localizes to centrosomes, centriolar satellites, and primary cilia; functions in protein trafficking and ciliogenesis
PMID: 28235840
4
CCDC66 regulates mitotic progression via spindle assembly and kinetochore-fiber integrity, and cytokinesis through central spindle organization; functions through microtubule nucleation and bundling
PMID: 35849559
5
CCDC66 dysfunction contributes to Joubert syndrome through effects on ciliary stability and axonemal modifications; identified as interaction partner of ARMC9
PMID: 32453716
6
Plasma circ-CCDC66 shows diagnostic potential as a colorectal cancer biomarker with high sensitivity and specificity
PMID: 40181128
7
CCDC66 centrosomal and ciliary targeting requires microtubule-dependent transport, centriolar satellites, and molecular motors
PMID: 31582766
Disease Associationsⓘ20
mathematical abilityOpen Targets
0.35Weak
crush injuryOpen Targets
0.30Weak
sign or symptomOpen Targets
0.29Weak
Chest painOpen Targets
0.27Weak
gastric ulcerOpen Targets
0.26Weak
hemorrhageOpen Targets
0.26Weak
Inguinal herniaOpen Targets
0.18Weak
deep vein thrombosisOpen Targets
0.12Weak
respiratory system diseaseOpen Targets
0.12Weak
Eczematoid dermatitisOpen Targets
0.12Weak
Abnormal thrombosisOpen Targets
0.10Weak
allergic diseaseOpen Targets
0.10Weak
Abnormality of refractionOpen Targets
0.09Suggestive
Blackfan-Diamond anemiaOpen Targets
0.08Suggestive
cervical cancerOpen Targets
0.08Suggestive
papillary thyroid carcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.07Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.07Suggestive
inosine triphosphatase deficiencyOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCDC14Protein interaction83%XRN2Protein interaction71%PCNTShared pathway21%MZT1Shared pathway17%ARMC9Shared pathway17%TXNDC15Shared pathway17%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
82%
Lung
47%
Heart
43%
Liver
39%
Brain
22%
Gene Interaction Network
Click a node to explore
CCDC66CCDC14XRN2PCNTMZT1ARMC9TXNDC15
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt A2RUB6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.14LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.95 [0.81–1.14]
RankingsWhere CCDC66 stands among ~20K protein-coding genes
  • #10,141of 20,598
    Most Researched40
  • #11,750of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedCCDC66
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CCDC66 regulation of cytoskeleton and cilia stability is important for signaling and epithelial organization.
PMID: 40729374
PLoS Biol · 2025
1.00
2
Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome.
PMID: 32453716
J Clin Invest · 2020
0.90
3
CCDC66 regulates primary cilium length and signaling via interactions with transition zone and axonemal proteins.
PMID: 36606424
J Cell Sci · 2023
0.80
4
The ciliopathy protein CCDC66 controls mitotic progression and cytokinesis by promoting microtubule nucleation and organization.
PMID: 35849559
PLoS Biol · 2022
0.70
5
Exploring the diagnostic potential of plasma circ-CCDC66 in colorectal cancer.
PMID: 40181128
Sci Rep · 2025
0.60