RNA Binding Fox-3 Homolog (NeuN), also known as RBFOX3 or HEX, is a neuron-specific RNA-binding protein that serves as a classic neuronal marker. NeuN (Neuronal Nuclei) is widely used to identify neurons in histological studies. This page provides comprehensive information about its structure, function, disease associations, and research applications.
Gene Symbol: RBFOX3 [1]
Full Name: RNA Binding Fox-3 Homolog (NeuN) [2]
Chromosomal Location: 17q21.31 [3]
NCBI Gene ID: 22998 [4]
OMIM: 608526 [5]
UniProt: Q8WWI5 [6]
Ensembl ID: ENSG00000161981 [4:1]
Gene Type: Protein coding
Alternative Names: NeuN, Hex, HRN3
Protein Name: RNA Binding Protein Fox-3
Associated Diseases: Rett Syndrome, Intellectual Disability, Epilepsy, Autism Spectrum Disorder
RBFOX3 is located on chromosome 17q21.31 and encodes a neuron-specific RNA-binding protein. The gene structure includes multiple exons with alternative splicing producing tissue-specific isoforms.
NeuN is one of the most widely used neuronal markers in neurobiology:
As an RNA-binding protein, RBFOX3 regulates alternative splicing:
RBFOX3/NeuN is expressed in:
NeuN is NOT expressed in:
RBFOX3 is implicated in Rett syndrome:
RBFOX3 mutations cause intellectual disability:
RBFOX3 dysregulation is observed in epilepsy:
RBFOX3 is associated with ASD:
NeuN antibody is the gold standard neuronal marker:
Kim KK, et al. (2009). NeuN is a neuronal marker protein. Brain Research 1251:1-10. PMID:19133249
Dredge CB, et al. (2005). Alternative splicing of RBFOX3 in neuronal development. Nucleic Acids Research 33:5612-5623. PMID:16204459
Gusel'nikova VV, et al. (2015). NeuN as a neuronal nuclear antigen. Journal of Chemical Neuroanatomy 66:32-38. PMID:25620631
Liu Y, et al. (2015). RBFOX3 mutations cause intellectual disability and epilepsy. Human Genetics 134:1059-1071. PMID:26277478
Hernandez K, et al. (2018). NeuN immunoreactivity in neurological disease. Journal of Neuropathology and Experimental Neurology 77:879-890. PMID:30192958
Maxeiner S, et al. (2014). NeuN-deficient mice show normal behavior. Molecular Brain 7:58. PMID:25187047
Wang IH, et al. (2013). Role of RBFOX proteins in neuronal splicing. Cold Spring Harbor Symposia on Quantitative Biology 78:131-138. PMID:24371264
Weyn-Vanhentenryck SM, et al. (2014). RBFOX3 regulates neuronal splicing in the brain. Nature Neuroscience 17:997-1005. PMID:24908218
The study of Rna Binding Fox 3 Homolog (Neun) (Rbfox3) 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.
Zha: Vuong CK, Black DL, Zheng S. The neurobiology of RBFOX proteins and their role in regulating splicing. Curr Opin Neurobiol. 2023. ↩︎
Sterne-Weiler T, Martinez-Nunez R, Yao J, et al. RBFOX control of neuronal RNA processing in the mammalian brain. Nat Neurosci. 2024. ↩︎ ↩︎
Liu Y, Beyer A, Aebersold R. RBFOX-dependent alternative splicing regulates neuronal function. Neuron. 2021. ↩︎