CBX1
protein-codingchromobox 1, the group of Chromobox family
Gene summary
This gene encodes a highly conserved nonhistone protein, which is a member of the heterochromatin protein family . The protein is enriched in the heterochromatin and associated with centromeres. The protein has a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues, and a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins. The protein may play an important role in the epigenetic control of chromatin structure and gene expression. Several related pseudogenes are located on chromosomes 1, 3, and X. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CBX1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001127228.2. 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 | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001120700.1 | 4 | MANE Select | |
| Ensembl | ENSP00000225603.4 | 4 | MANE Select | |
| RefSeq | NP_006798.1 | 4 | Standard | |
| Ensembl | ENSP00000377060.3 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cellular response to DNA damage stimulus
- negative regulation of transcription, DNA-templated
Molecular Function
- chromatin binding
- protein binding
- enzyme binding
- protein homodimerization activity
- histone methyltransferase binding
Cellular Component
- chromosome, centromeric region
- nuclear chromosome, telomeric region
- chromatin
- female pronucleus
- male pronucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393408
- Coding exons
- 4
- Length
- 31470
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.54 | 28 | 99.3 | 0.282 | 0.00000532 | 1219 |
| Missense (PolyPhen) | 5 | 41.762 | 0.11973 | 506 | ||
| Synonymous | 0.907 | 30 | 37.0 | 0.810 | 0.00000202 | 325 |
| Loss of Function | 3.14 | 0 | 11.5 | 0.00 | 7.17e-7 | 128 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane. {ECO:0000250|UniProtKB:P83917}.;
Intolerance Scores
- LoFtool
- 0.169
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.961