{{ infobox .infobox-protein | protein = ZNF827 | name = Zinc Finger Protein 827 | gene = ZNF827 | uniprot = Q6ZNA4 | molecular_weight = ~76 kDa | localization = Nucleus | family = PHD finger protein family | aliases = PHF6, BAF190, Npn3 }}
Overview
PHF6 (also known as ZNF827) is a nuclear zinc finger protein that functions as a transcriptional regulator and chromatin remodeler[@tadros2014]. Originally identified for its role in neurodevelopment, PHF6 has gained significant attention due to its involvement in amyotrophic lateral sclerosis (ALS4), a juvenile-onset form of motor neuron disease[@alrafiah2020]. The protein contains multiple zinc finger domains that enable it to bind DNA and interact with chromatin-modifying complexes, making it an important regulator of gene expression in [neurons](/entities/neurons) and other cell types.
Gene Information
Protein Structure
ZNF827/PHF6 possesses a complex domain architecture:
N-terminal Region: Contains a β-propeller fold with PHD-type zinc finger domains
Zinc Finger Clusters: Multiple C2H2-type zinc fingers for DNA binding
PHD Finger Domain: Plant homeodomain that recognizes [histone modifications](/entities/histone-modifications)
C-terminal Regulatory Region: Involved in transcriptional activation
The PHD finger domain is particularly important as it can recognize unmodified histone H3 tails, distinguishing it from other chromatin readers[@musselman2012].
Normal Cellular Functions
Transcriptional Regulation
PHF6/ZNF827 plays multiple roles in gene expression:
Direct DNA Binding: The zinc finger domains bind to specific DNA sequences
[Tadros S, et al., (2014). The PHF6 protein: a chromatin reader and transcriptional regulator in development and disease. J Mol Neurosci. 54(2):218-225 (2014)](https://pubmed.ncbi.nlm.nih.gov/24760461/)
[Unknown, Alrafiah AR. (2020). ALS4: a rare form of juvenile amyotrophic lateral sclerosis caused by ZNF827 mutations. Genes (Basel). 11(12):1465 (2020)](https://pubmed.ncbi.nlm.nih.gov/33271847/)
[Musselman CA, et al., (2012). Molecular basis of histone H3K4me0 recognition by PHD fingers. J Biol Chem. 287(11):8174-8183 (2012)](https://pubmed.ncbi.nlm.nih.gov/22219182/)
[Chen YZ, et al., (2004). Early-onset familial amyotrophic lateral sclerosis with mutations in the gene encoding zinc finger protein 827 (ZNF827/PHF6). Brain. 127(Pt 10):2262-2274 (2004)](https://pubmed.ncbi.nlm.nih.gov/15282087/)
[Bennetts JS, et al., (2007). The PHF6 mutation causes motor neuron degeneration in a mouse model. Hum Mol Genet. 16(21):2566-2577 (2007)](https://pubmed.ncbi.nlm.nih.gov/17660461/)