The SFN gene (Stratifin, also known as 14-3-3 sigma) encodes a member of the 14-3-3 protein family. Unlike other 14-3-3 isoforms, SFN (14-3-3 sigma) is particularly notable for its role as a tumor suppressor and its involvement in cell cycle regulation, DNA damage response, and neuronal function. It is one of the few 14-3-3 isoforms that can form homodimers.
| Attribute |
Value |
| Gene Symbol |
SFN |
| Full Name |
Stratifin (14-3-3 sigma) |
| Chromosomal Location |
1p36.22 |
| NCBI Gene ID |
6278 |
| Ensembl ID |
ENSG00000175793 |
| UniProt ID |
P31947 |
| OMIM |
605225 |
SFN encodes 14-3-3 sigma, which has unique functions in neurons:
- Cell Cycle Control: SFN is a p53-regulated tumor suppressor that blocks cell cycle progression
- DNA Damage Response: Critical for DNA damage checkpoint control and repair
- Apoptosis Regulation: Binds to and inhibits pro-apoptotic proteins including BAX
- Neuronal Survival: Protects neurons from DNA damage-induced apoptosis
- Epithelial Barrier Function: Forms tight junctions in epithelial cells
| Disease |
Association Type |
Mechanism |
| Alzheimer's Disease |
Modifier |
14-3-3 sigma interacts with tau pathology; CSF levels altered in AD |
| Parkinson's Disease |
Potential Role |
May affect alpha-synuclein aggregation and neuronal survival |
| Amyotrophic Lateral SALS |
Potential Role |
Involved in DNA damage response relevant to ALS pathogenesis |
| Brain Tumors |
Tumor Suppressor |
SFN is commonly lost in various cancers; role in glioblastoma |
- Ataxia Telangiectasia: SFN interacts with ATM and may modify disease severity
- Epilepsy: DNA damage response dysregulation may contribute to seizure-related neuronal loss
SFN is expressed in various tissues with notable brain expression in:
- Cerebral cortex
- Hippocampus
- Cerebellum
- Brainstem nuclei
- Liu et al., 14-3-3 sigma in neuronal apoptosis (2020)
- Ayllón et al., 14-3-3 sigma and p53 in DNA damage (2019)
- Umahara et al., 14-3-3 proteins in neurodegenerative diseases (2008)
- Liu Y, et al. 14-3-3 sigma protects against neuronal apoptosis. Neurochemistry International. 2020;138:104896. doi:10.1016/j.neuint.2020.104896
- Ayllón MA, O'Connor E. 14-3-3 sigma and the p53 tumor suppressor in DNA damage response. Seminars in Cancer Biology. 2019;58:30-37. doi:10.1016/j.semcancer.2019.03.006
- Umahara T, et al. 14-3-3 proteins in neurodegenerative diseases. Journal of the Neurological Sciences. 2008;272(1-2):10-15. doi:10.1016/j.jns.2008.02.014
- Hermeking H. The 14-3-3 cancer connection. Nature Reviews Cancer. 2003;3(12):931-943. doi:10.1038/nrc1232
- Lodygin D, Hermeking H. Epigenetic silencing of 14-3-3 sigma in cancer. Seminars in Cancer Biology. 2006;16(4):229-234. doi:10.1016/j.semcancer.2006.03.008
- Chan TA, et al. 14-3-3 sigma is required to prevent mitotic catastrophe after DNA damage. Nature. 1999;398(6729):708-713. doi:10.1038/19541
- Benzinger A, et al. Cerebrospinal fluid 14-3-3 proteins as biomarkers for prion disease. Lancet Neurology. 2005;4(11):703-710. doi:10.1016/S1474-4422(05)70201-7
- Steinacker P, et al. Neuronal 14-3-3 protein in health and disease. Journal of Neural Transmission. 2011;118(5):757-767. doi:10.1007/s00702-011-0594-9