CHTOP
protein-codingchromatin target of PRMT1, the group of Transcription and export complex 1 subunits
Gene summary
This gene encodes a small nuclear protein that is characterized by an arginine and glycine rich region. This protein may have an important role in the regulation of fetal globin gene expression and in the activation of estrogen-responsive genes. A recent study reported that this protein binds 5-hydroxymethylcytosine (5hmC) and associates with an arginine methyltransferase complex (methylosome), which promotes methylation of arginine 3 of histone H4 (H4R3) and activation of genes involved in glioblastomagenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2015]
- C1orf77
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.3 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 CHTOP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015607.4. 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 | 1 | ||||
| missense | 38 | 1 | 39 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 38 | 2 | 0 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056422.2 | 5 | MANE Select | |
| Ensembl | ENSP00000357683.3 | 5 | MANE Select | |
| RefSeq | NP_001193541.1 | 5 | Standard | |
| RefSeq | NP_001231593.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- RNA Polymerase II Transcription
- Metabolism of RNA
- Cleavage of Growing Transcript in the Termination Region
- RNA Polymerase II Transcription Termination
Biological Process
- RNA export from nucleus
- mRNA export from nucleus
- positive regulation of cell population proliferation
- positive regulation of histone methylation
- mRNA 3'-end processing
Molecular Function
- RNA binding
- protein binding
- methyl-CpG binding
Cellular Component
- transcription export complex
- nucleoplasm
- nucleolus
- nuclear speck
- cytoplasmic ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368694
- Coding exons
- 5
- Length
- 12258
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125739
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.70 | 105 | 167 | 0.630 | 0.0000110 | 1536 |
| Missense (PolyPhen) | 0 | 0.48393 | 0 | 4 | ||
| Synonymous | 0.138 | 60 | 61.4 | 0.978 | 0.00000360 | 567 |
| Loss of Function | 3.27 | 3 | 17.9 | 0.167 | 0.00000155 | 136 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays an important role in the ligand-dependent activation of estrogen receptor target genes (PubMed:19858291). May play a role in the silencing of fetal globin genes (PubMed:20688955). Recruits the 5FMC complex to ZNF148, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (By similarity). Plays an important role in the tumorigenicity of glioblastoma cells. Binds to 5- hydroxymethylcytosine (5hmC) and associates with the methylosome complex containing PRMT1, PRMT5, MEP50 and ERH. The CHTOP- methylosome complex associated with 5hmC is recruited to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis (PubMed:25284789). {ECO:0000250|UniProtKB:Q9CY57, ECO:0000269|PubMed:19858291, ECO:0000269|PubMed:20688955, ECO:0000269|PubMed:25284789}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 39.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |