CBX5
protein-codingchromobox 5, the group of Chromobox family|MicroRNA protein coding host genes
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 encoded product is involved in the formation of functional kinetochore through interaction with essential kinetochore proteins. The gene has a pseudogene located on chromosome 3. 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 ~49.2 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 CBX5 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012117.3. 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 | 0 | |||||
| missense | 2 | 2 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 5 | 0 | 0 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036249.1 | 4 | MANE Select | |
| Ensembl | ENSP00000209875.4 | 4 | MANE Select | |
| RefSeq | NP_001120793.1 | 4 | Standard | |
| RefSeq | NP_001120794.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Transcriptional Regulation by E2F6
- Generic Transcription Pathway
- Factors involved in megakaryocyte development and platelet production
- SUMOylation of chromatin organization proteins
Biological Process
- negative regulation of transcription by RNA polymerase II
- cellular response to DNA damage stimulus
- blood coagulation
- viral process
- negative regulation of transcription, DNA-templated
Molecular Function
- chromatin binding
- protein binding
- protein binding, bridging
- methylated histone binding
- identical protein binding
Cellular Component
- histone deacetylase complex
- kinetochore
- nuclear chromosome, telomeric region
- nucleus
- nuclear envelope
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000209875
- Coding exons
- 4
- Length
- 49163
- 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 | 2.53 | 30 | 102 | 0.295 | 0.00000512 | 1277 |
| Missense (PolyPhen) | 8 | 51.806 | 0.15442 | 634 | ||
| Synonymous | 0.320 | 34 | 36.5 | 0.933 | 0.00000189 | 324 |
| Loss of Function | 2.71 | 0 | 8.55 | 0.00 | 3.57e-7 | 121 |
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 that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression. In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph). Can interact with lamin-B receptor (LBR). This interaction can contribute to the association of the heterochromatin with the inner nuclear membrane. Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins. {ECO:0000269|PubMed:19783980}.;
Recessive Scores
- pRec
- 0.413
Intolerance Scores
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |