PHF6: PHD Finger Protein 6
A chromatin-associated tumor suppressor gene implicated in T-cell acute lymphoblastic leukemia and Börjeson-Forssman-Lehmann syndrome
Gene Information Card
| Symbol | PHF6 |
|---|---|
| Full Name | PHD finger protein 6 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq26.3 |
| NCBI Gene ID | 84295 ncbi.nlm.nih.gov/gene/84295 |
| Ensembl ID | ENSG00000156531 |
| UniProt ID | Q8IWS0 |
| OMIM ID | 300414 |
| HGNC ID | 18145 |
| Aliases | BFLS, CENP-31, PHD finger protein 6 |
Description
PHF6 (PHD finger protein 6) encodes a protein containing two plant homeodomain (PHD) zinc finger domains, which are characteristic of chromatin-associated proteins involved in transcriptional regulation. The PHF6 protein is predominantly nuclear and is thought to function as a tumor suppressor by modulating chromatin structure and gene expression. Germline loss-of-function mutations in PHF6 cause Börjeson-Forssman-Lehmann syndrome (BFLS), an X-linked intellectual disability disorder. Somatic mutations, particularly truncating and missense variants, are recurrently found in T-cell acute lymphoblastic leukemia (T-ALL) and, less frequently, in acute myeloid leukemia (AML) and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Börjeson-Forssman-Lehmann syndrome (BFLS) | Germline loss-of-function mutations in PHF6 lead to reduced protein function, causing X-linked intellectual disability, obesity, and facial dysmorphism. | OMIM #301900; multiple case reports and family studies |
| T-cell acute lymphoblastic leukemia (T-ALL) | Somatic truncating and missense mutations in PHF6 (often co-occurring with NOTCH1 mutations) impair its tumor suppressor activity, contributing to leukemogenesis. | COSMIC; Liu et al., Nat Genet 2010; Van Vlierberghe et al., Nat Genet 2010 |
| Acute myeloid leukemia (AML) | Recurrent somatic mutations in PHF6, though less frequent than in T-ALL, are associated with myeloid malignancies. | COSMIC; Patel et al., N Engl J Med 2012 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Low |
| Heart | 5.1 | Low |
| Lung | 6.3 | Low |
| Liver | 4.7 | Low |
| Kidney | 7.0 | Low |
| Testis | 12.5 | Medium |
| Bone marrow | 9.8 | Low |
| Lymph node | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 11.2 | Embryonic kidney; moderate expression |
| K562 | 8.5 | Chronic myeloid leukemia; low expression |
| Jurkat | 14.3 | T-cell leukemia; medium expression |
| MCF7 | 7.9 | Breast cancer; low expression |
| HepG2 | 6.8 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.808C>T (p.Arg270*) | Nonsense | Recurrent in T-ALL (~5-10%) | Truncation; loss of function |
| c.1000C>T (p.Arg334*) | Nonsense | Recurrent in T-ALL | Truncation; loss of function |
| c.2T>C (p.Met1?) | Missense (start loss) | Rare in BFLS | Loss of translation initiation; loss of function |
| c.1096C>T (p.Arg366Trp) | Missense | Reported in BFLS | Impaired chromatin binding; loss of function |
| c.1003G>A (p.Gly335Arg) | Missense | Somatic in T-ALL | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Majority of PHF6 mutations in both BFLS and T-ALL are loss-of-function (nonsense, frameshift, splice-site, or missense disrupting PHD domains), leading to reduced protein stability or impaired chromatin binding.
Gain of Function (GOF)
No evidence of gain-of-function mutations in PHF6.
Dominant Negative (DN)
Not established; PHF6 is X-linked and hemizygous loss in males is sufficient for disease, suggesting haploinsufficiency rather than dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (via interaction with NOTCH1 in T-ALL)
• Chromatin remodeling
Protein Summary
PHF6 is a 365-amino-acid nuclear protein containing two PHD zinc finger domains that mediate interactions with histones and chromatin. It is ubiquitously expressed, with higher levels in the brain and testis. The protein is involved in transcriptional regulation and chromatin remodeling. Loss of PHF6 function is associated with X-linked intellectual disability (BFLS) and contributes to the pathogenesis of T-cell acute lymphoblastic leukemia through dysregulation of gene expression programs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHF6 Knockout HEK293 Cell Line | EDJ-KQ2475 | Human | 84295 | Details Get a Quote |
| PHF6 Knockout A-549 Cell Line | EDJ-KQ23041 | Human | 84295 | Details Get a Quote |
| PHF6 Knockout HCT 116 Cell Line | EDJ-KQ23042 | Human | 84295 | Details Get a Quote |
| PHF6 Knockout HeLa Cell Line | EDJ-KQ23043 | Human | 84295 | Details Get a Quote |
