PHF1
protein-codingPHD finger protein 1, the group of PHD finger proteins|Tudor domain containing
Gene summary
This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PHF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024165.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 6 | 7 | |||
| missense | 59 | 1 | 60 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 61 | 7 | 0 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_077084.2 | 14 | MANE Select | |
| Ensembl | ENSP00000363640.3 | 14 | MANE Select | |
| RefSeq | NP_002627.2 | 13 | Standard | |
| Ensembl | ENSP00000363636.3 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Epigenetic regulation of gene expression
- Gene expression (Transcription)
- PRC2 methylates histones and DNA
Biological Process
- chromatin organization
- cellular response to DNA damage stimulus
- negative regulation of gene expression, epigenetic
- positive regulation of transcription, DNA-templated
- negative regulation of histone H3-K27 methylation
Molecular Function
- DNA-binding transcription factor activity
- protein binding
- nucleosome binding
- methylated histone binding
- sequence-specific DNA binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- centrosome
- ESC/E(Z) complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374516
- Coding exons
- 14
- Length
- 6055
- Individuals with no LoFs
- 125744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125748
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.80 | 248 | 341 | 0.726 | 0.0000202 | 3608 |
| Missense (PolyPhen) | 32 | 97.53 | 0.3281 | 1074 | ||
| Synonymous | 0.0836 | 122 | 123 | 0.990 | 0.00000607 | 1209 |
| Loss of Function | 4.83 | 2 | 31.0 | 0.0645 | 0.00000158 | 349 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci (PubMed:18285464 and PubMed:23273982). According to another report, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2 (PubMed:23142980). Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53. {ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:18385154, ECO:0000269|PubMed:23142980, ECO:0000269|PubMed:23150668, ECO:0000269|PubMed:23273982}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving PHF1 may be a cause of endometrial stromal tumors. Translocation t(6;7)(p21;p22) with JAZF1. Translocation t(1;6)(p34;p21) with MEAF6. {ECO:0000269|PubMed:16397222, ECO:0000269|PubMed:22761769}.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.252
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.960
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |