PCGF6
protein-codingpolycomb group ring finger 6, the group of Polycomb group ring fingers|Ring finger proteins
Gene summary
The protein encoded by this gene contains a RING finger motif, which is most closely related to those of polycomb group (PcG) proteins RNF110/MEL-18 and BMI1. PcG proteins are known to form protein complexes and function as transcription repressors. This protein has been shown to interact with some PcG proteins and act as a transcription repressor. The activity of this protein is found to be regulated by cell cycle dependent phosphorylation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
- RNF134
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.3 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 PCGF6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001011663.2. 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 | 2 | 1 | 3 | |||
| missense | 51 | 51 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 55 | 1 | 0 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001011663.1 | 10 | MANE Select | |
| Ensembl | ENSP00000358862.3 | 10 | MANE Select | |
| RefSeq | NP_115530.2 | 7 | Standard | |
| Ensembl | ENSP00000338845.4 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
- Gene expression (Transcription)
- Transcriptional Regulation by E2F6
- Generic Transcription Pathway
- RNA Polymerase II Transcription
Biological Process
- negative regulation of transcription by RNA polymerase II
- histone H2A-K119 monoubiquitination
- negative regulation of transcription, DNA-templated
- inactivation of X chromosome by genetic imprinting
- negative regulation of G0 to G1 transition
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA binding
- DNA-binding transcription factor activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- PcG protein complex
- PRC1 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369847
- Coding exons
- 10
- Length
- 48339
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125711
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.779 | 141 | 170 | 0.832 | 0.00000832 | 2236 |
| Missense (PolyPhen) | 13 | 17.804 | 0.73017 | 216 | ||
| Synonymous | 0.136 | 58 | 59.3 | 0.978 | 0.00000276 | 676 |
| Loss of Function | 1.97 | 10 | 19.3 | 0.517 | 0.00000105 | 248 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor (PubMed:12167161). May modulate the levels of histone H3K4Me3 by activating KDM5D histone demethylase (PubMed:17320162). Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:12167161). Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity (PubMed:26151332). {ECO:0000269|PubMed:12167161, ECO:0000269|PubMed:17320162, ECO:0000269|PubMed:26151332}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.709
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.743
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |