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GeneE
4 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DRC2
dynein regulatory complex subunit 2
Chromosome 12 Β· 12q13.12
NCBI Gene: 85478Ensembl: ENSG00000139537.12HGNC: HGNC:29937UniProt: B4DXQ7
23PubMed Papers
21Diseases
0Drugs
20Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cilium assemblyciliary basal bodyregulation of cilium movementprotein bindingprimary ciliary dyskinesiagenetic disordersmoking initiationgastric cancer
✦AI Summary

DRC2 (dynein regulatory complex subunit 2), also known as CCDC65, is a critical structural component of the nexin-dynein regulatory complex (N-DRC), which controls ciliary and flagellar motility 1. DRC2 functions as a central hub for N-DRC assembly, with its C-terminal region essential for coassembling with DRC1 to form the base plate that attaches to outer doublet microtubules 1. This assembly stabilizes multiple associated axonemal structures, including inner dynein arms, radial spokes, and the calmodulin-spoke complex 1. Mutations in DRC2/CCDC65 cause primary ciliary dyskinesia (PCD), a genetic ciliopathy characterized by impaired ciliary function and dyskinetic cilia beating 2. Notably, DRC2 mutations can produce PCD without detectable ultrastructural ciliary abnormalities 2, highlighting the functional role of N-DRC components. Loss of DRC2 disrupts assembly of multiple N-DRC subunits and destabilizes associated dynein arms 1. Beyond respiratory cilia, DRC2 is essential for sperm flagellum structure and function 3. Mutations in CCDC65 cause multiple morphological abnormalities of sperm flagella (MMAF) with asthenozoospermia, demonstrating that DRC2 function extends to male reproductive biology 3. These findings establish DRC2 as a fundamental regulator of axonemal dynamics with implications for both respiratory ciliopathies and male infertility.

Sources cited
1
DRC2 C-terminal region is critical for DRC2-DRC1 coassembly, N-DRC base plate formation, outer doublet attachment, and stabilization of inner dynein arms, radial spokes, and calmodulin-spoke complex
PMID: 29167384
2
CCDC65/DRC2 mutations cause multiple morphological abnormalities of sperm flagella (MMAF) and asthenozoospermia; CCDC65 is required for sperm flagellum structure
PMID: 37975235
3
CCDC65 mutations cause primary ciliary dyskinesia with dyskinetic cilia beating without detectable ultrastructural defects; CCDC65 is required for normal cilia function and associates with GAS8
PMID: 23991085
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
primary ciliary dyskinesiaOpen Targets
0.71Strong
genetic disorderOpen Targets
0.19Weak
smoking initiationOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
age-related macular degenerationOpen Targets
0.07Suggestive
X-linked retinal dysplasiaOpen Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
retinitis pigmentosaOpen Targets
0.05Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
reticular dystrophy of the retinal pigment epitheliumOpen Targets
0.05Suggestive
Familial drusenOpen Targets
0.04Suggestive
X-linked retinoschisisOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
Sorsby fundus dystrophyOpen Targets
0.04Suggestive
Sorsby's fundus dystrophyOpen Targets
0.04Suggestive
age related macular degeneration 11Open Targets
0.04Suggestive
age related macular degeneration 2Open Targets
0.04Suggestive
age related macular degeneration 4Open Targets
0.04Suggestive
Ciliary dyskinesia, primary, 27UniProt
Pathogenic Variants20
NM_033124.5(DRC2):c.877_878del (p.Ile293fs)Pathogenic
Primary ciliary dyskinesia 27|Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 293
NM_033124.5(DRC2):c.494del (p.Glu165fs)Pathogenic
Primary ciliary dyskinesia 27|not provided
β˜…β˜…β˜†β˜†2018β†’ Residue 165
NM_033124.5(DRC2):c.195G>A (p.Trp65Ter)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2026β†’ Residue 65
NM_033124.5(DRC2):c.339C>A (p.Tyr113Ter)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2026β†’ Residue 113
NM_033124.5(DRC2):c.807+1G>CLikely pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2025
NM_033124.5(DRC2):c.710_711del (p.Thr237fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2025β†’ Residue 237
NM_033124.5(DRC2):c.739del (p.Leu247fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2025β†’ Residue 247
NM_033124.5(DRC2):c.968_971del (p.Val323fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2025β†’ Residue 323
NM_033124.5(DRC2):c.805C>T (p.Gln269Ter)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2025β†’ Residue 269
NM_033124.5(DRC2):c.301-2A>CLikely pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2024
NM_033124.5(DRC2):c.205dup (p.Leu69fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2024β†’ Residue 69
NM_033124.5(DRC2):c.339C>G (p.Tyr113Ter)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2024β†’ Residue 113
NM_033124.5(DRC2):c.966dup (p.Val323fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2024β†’ Residue 323
NM_033124.5(DRC2):c.718C>T (p.Arg240Ter)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2024β†’ Residue 240
NM_033124.5(CCDC65):c.876T>G (p.Tyr292Ter)Likely pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2023β†’ Residue 292
NM_033124.5(DRC2):c.699del (p.Asn232_Tyr233insTer)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2022β†’ Residue 232
NM_033124.5(DRC2):c.469dup (p.Arg157fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2022β†’ Residue 157
NM_033124.5(DRC2):c.904_905del (p.Val302fs)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2022β†’ Residue 302
NM_033124.5(DRC2):c.470+1G>ALikely pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2021
NM_033124.5(DRC2):c.658G>T (p.Glu220Ter)Pathogenic
Primary ciliary dyskinesia 27
β˜…β˜†β˜†β˜†2018β†’ Residue 220
View on ClinVar β†—
Related Genes
RSPH1Protein interaction99%DNAI1Protein interaction98%DNAI2Protein interaction98%DNAH5Protein interaction98%DNAH11Protein interaction94%RSPH4AProtein interaction92%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
88%
Lung
46%
Ovary
34%
Liver
28%
Heart
15%
Gene Interaction Network
Click a node to explore
DRC2RSPH1DNAI1DNAI2DNAH5DNAH11RSPH4A
PROTEIN STRUCTURE
Preparing viewer…
PDB8J07 Β· 4.10 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.00LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.77 [0.59–1.00]
RankingsWhere DRC2 stands among ~20K protein-coding genes
  • #13,405of 20,598
    Most Researched23
  • #2,208of 5,498
    Most Pathogenic Variants20
  • #9,738of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedDRC2
Sources retrieved4 papers
Response timeβ€”
πŸ“„ Sources
4
1
DRC2/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility.
PMID: 29167384
Mol Biol Cell Β· 2018
1.00
2
CCDC65, encoding a component of the axonemal Nexin-Dynein regulatory complex, is required for sperm flagellum structure in humans.
PMID: 37975235
Clin Genet Β· 2024
0.75
3
CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia.
PMID: 23991085
PLoS One Β· 2013
0.50
4
Deep Learning Radiomic Analysis of MRI Combined with Clinical Characteristics Diagnoses Placenta Accreta Spectrum and its Subtypes.
PMID: 38390981
J Magn Reson Imaging Β· 2024
0.25