PHF8 Gene: PHD Finger Protein 8
A histone lysine demethylase involved in transcriptional regulation and neurodevelopment
Gene Information Card
| Symbol | PHF8 |
|---|---|
| Full Name | PHD finger protein 8 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.22 |
| NCBI Gene ID | 23133 ncbi.nlm.nih.gov/gene/23133 |
| Ensembl ID | ENSG00000172977 |
| UniProt ID | Q9UPP1 |
| OMIM ID | 300560 |
| HGNC ID | 20672 |
| Aliases | KIAA1111, ZNF422, MRXSSD, JHDM1F, KDM7B |
Description
PHF8 (PHD finger protein 8) encodes a histone lysine demethylase that specifically demethylates mono- and dimethylated histone H3 lysine 9 (H3K9me1/me2) and H3K27me2, and also H4K20me1. It contains a PHD finger domain and a JmjC domain, and is involved in transcriptional activation, cell cycle regulation, and neurodevelopment. Mutations in PHF8 cause X-linked intellectual disability with cleft lip/palate (Siderius-Hamel syndrome).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Siderius-Hamel syndrome | Loss-of-function mutations in PHF8 impair histone demethylase activity, leading to dysregulation of gene expression during neurodevelopment and craniofacial development. | OMIM #300560; PMID: 15992777 |
| X-linked intellectual disability | Nonsense and missense mutations in PHF8 reduce or abolish demethylase activity, affecting neuronal gene expression. | ClinVar; PMID: 15992777 |
| Cleft lip/palate | PHF8 mutations disrupt craniofacial development pathways, possibly through altered H3K9me2 demethylation at key developmental genes. | OMIM #300560; PMID: 15992777 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Liver | 4.2 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells |
| SH-SY5Y | 18.7 | Neuroblastoma cells |
| HeLa | 9.4 | Cervical carcinoma cells |
| K562 | 7.1 | Leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely no protein |
| c.826C>T (p.Arg276*) | Nonsense | Rare | Premature stop, loss of JmjC domain |
| c.1099G>A (p.Gly367Arg) | Missense | Rare | Reduced demethylase activity |
| c.1462C>T (p.Arg488Trp) | Missense | Rare | Impaired substrate binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg276*) lead to truncated protein lacking the catalytic JmjC domain, resulting in complete loss of demethylase activity.
Gain of Function (GOF)
No gain-of-function mutations reported for PHF8.
Dominant Negative (DN)
No dominant-negative mutations reported; PHF8 is X-linked and loss-of-function is typically recessive in females.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Histone demethylation
• Transcriptional regulation by histone modifications
• Chromatin organization
Protein Summary
PHF8 is a 1060-amino acid protein containing an N-terminal PHD finger domain that recognizes histone H3K4me3, and a C-terminal JmjC domain that catalyzes demethylation of H3K9me1/me2, H3K27me2, and H4K20me1. It acts as a transcriptional coactivator by removing repressive histone marks, and is essential for normal brain development and craniofacial morphogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHF8 Knockout HEK293 Cell Line | EDJ-KQ7848 | Human | 23133 | Details Get a Quote |
| PHF8 Knockout A-549 Cell Line | EDJ-KQ32076 | Human | 23133 | Details Get a Quote |
| PHF8 Knockout HCT 116 Cell Line | EDJ-KQ33402 | Human | 23133 | Details Get a Quote |
| PHF8 Knockout HeLa Cell Line | EDJ-KQ33403 | Human | 23133 | Details Get a Quote |
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