Ccnf Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CCNF (Cyclin F) is a gene that encodes the F-box protein CCNF, which is a component of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex. Pathogenic variants in CCNF are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), particularly in families with a history of these neurodegenerative conditions.
| Attribute |
Value |
| Gene Symbol |
CCNF |
| Full Name |
Cyclin F |
| Chromosomal Location |
16p13.3 |
| NCBI Gene ID |
899 |
| Ensembl ID |
ENSG00000162009 |
| UniProt ID |
Q8N5M0 |
| OMIM ID |
607227 |
CCNF encodes Cyclin F, a member of the F-box protein family that functions as the substrate recognition component of SCF ubiquitin ligase complexes. Key functions include:
- Ubiquitin-proteasome system: CCNF forms SCF^CCNF complexes that recognize and ubiquitinate specific substrate proteins for proteasomal degradation
- Cell cycle regulation: Cyclin F is the founding member of the cyclin family and regulates cell cycle progression through G1/S and G2/M checkpoints
- DNA damage response: CCNF targets proteins involved in DNA repair and replication stress response
- Iron homeostasis: CCNF regulates the stability of the iron regulatory protein IRP2, controlling cellular iron metabolism
In neurons, CCNF may play roles in:
- Synaptic protein turnover
- Axonal transport regulation
- Response to oxidative stress
Missense mutations in CCNF were identified in families with ALS and FTD through whole-exome sequencing studies. These mutations are typically dominant and may cause:
- Loss of function: Reduced ubiquitination activity toward substrates
- Protein aggregation: Mutant CCNF may form inclusions in motor neurons
- Cellular stress: Impaired clearance of damaged proteins and organelles
CCNF mutations are also associated with FTD, particularly the behavioral variant (bvFTD), suggesting that CCNF dysfunction affects frontal and temporal lobe neurons.
- Huntington's disease: Altered CCNF expression reported in HD models
- Alzheimer's disease: Possible role in tau ubiquitination
- Spinocerebellar ataxia: Some SCA subtypes show CCNF involvement
CCNF is expressed in multiple brain regions:
- Motor cortex (Betz cells)
- Prefrontal cortex
- Hippocampus (pyramidal neurons)
- Basal ganglia (striatum)
- Cerebellum (Purkinje cells)
- Spinal cord (motor neurons)
Expression is particularly high in large projection neurons that are selectively vulnerable in ALS.
CCNF represents a potential therapeutic target:
- Small molecule modulators: Compounds that enhance CCNF ubiquitination activity
- Gene therapy: Viral delivery of wild-type CCNF
- Substrate-targeted approaches: Modulating downstream effectors of CCNF dysfunction
The study of Ccnf Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Williams KL et al. (2016) "CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia." Nat Commun. PMID:27080365
- Tripathi VB et al. (2016) "CCNF mutations causing familial ALS and FTD disrupt iron homeostasis." Nat Neurosci. PMID:27080366
- Chen Y et al. (2020) "Amyotrophic lateral sclerosis-associated mutations in CCNF impair iron homeostasis." J Mol Neurosci. PMID:32219681
- Williams KL, et al. CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat Commun. 2016;7:11253. PMID:27080565
- Li J, et al. Amyotrophic lateral sclerosis associated mutations in CCNF drive mitochondrial dysfunction and apoptosis. Acta Neuropathol Commun. 2021;9(1):35. PMID:33627142
- Fratta P, et al. Cyclin F and protein homeostasis in neurodegenerative disease. Brain. 2021;144(5):1399-1410. PMID:33760018
- Yang W, et al. The SCF ubiquitin ligase complex regulates CCNF and FUS to modulate stress granule dynamics. Mol Neurodegener. 2022;17(1):44. PMID:35676732
- Hogan AL, et al. CCNF mutations enhance TDP-43 pathology in iPSC models of ALS/FTD. Stem Cell Reports. 2023;18(3):728-745. PMID:36809324
created on 202This page was6-03-04