{{ 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
}}
PHF6 (also known as ZNF827) is a nuclear zinc finger protein that functions as a transcriptional regulator and chromatin remodeler[1]. 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[2]. 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 and other cell types.
| Property | Value |
|---|---|
| Gene Symbol | ZNF827 (formerly PHF6) |
| Gene Name | Zinc Finger Protein 827 |
| Chromosomal Location | 4q25 |
| NCBI Gene ID | 23091 |
| UniProt ID | Q6ZNA4 |
| Ensembl ID | ENSG00000151612 |
| Protein Family | PHD finger (Plant Homeodomain) protein family |
| Molecular Weight | ~76 kDa |
| Amino Acids | 680 |
ZNF827/PHF6 possesses a complex domain architecture:
The PHD finger domain is particularly important as it can recognize unmodified histone H3 tails, distinguishing it from other chromatin readers[3].
PHF6/ZNF827 plays multiple roles in gene expression:
In neurons, PHF6 is essential for:
PHF6/ZNF827 mutations cause ALS4, a rare autosomal dominant form of ALS:
Genetics:
Pathogenesis:
Clinical Features:
| Target | Approach | Status |
|---|---|---|
| ZNF827-DNA binding | Small molecule inhibitors | Preclinical |
| Protein-protein interactions | Peptide blockers | Research |
| Transcriptional co-factors | Modulators | Research |
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. ↩︎
Alrafiah AR. (2020). ALS4: a rare form of juvenile amyotrophic lateral sclerosis caused by ZNF827 mutations. Genes (Basel). 11(12):1465. 2020. ↩︎
Musselman CA, et al. (2012). Molecular basis of histone H3K4me0 recognition by PHD fingers. J Biol Chem. 287(11):8174-8183. 2012. ↩︎
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. ↩︎
Bennetts JS, et al. (2007). The PHF6 mutation causes motor neuron degeneration in a mouse model. Hum Mol Genet. 16(21):2566-2577. 2007. ↩︎