CBX3
protein-codingchromobox 3, the group of Chromobox family
Gene summary
At the nuclear envelope, the nuclear lamina and heterochromatin are adjacent to the inner nuclear membrane. The protein encoded by this gene binds DNA and is a component of heterochromatin. This protein also can bind lamin B receptor, an integral membrane protein found in the inner nuclear membrane. The dual binding functions of the encoded protein may explain the association of heterochromatin with the inner nuclear membrane. This protein binds histone H3 tails methylated at Lys-9 sites. This protein is also recruited to sites of ultraviolet-induced DNA damage and double-strand breaks. Two transcript variants encoding the same protein but differing in the 5' UTR, have been found for this gene.[provided by RefSeq, Mar 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.4 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 CBX3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016587.4. 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 | 9 | 9 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| 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_057671.2 | 5 | MANE Select | |
| Ensembl | ENSP00000379670.2 | 5 | MANE Select | |
| RefSeq | NP_001397795.1 | 4 | Standard | |
| RefSeq | NP_009207.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Exercise-induced Circadian Regulation
- ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
- Positive epigenetic regulation of rRNA expression
- Epigenetic regulation of gene expression
- Gene expression (Transcription)
Biological Process
- chromatin remodeling
- cellular response to DNA damage stimulus
- negative regulation of transcription, DNA-templated
- rhythmic process
- negative regulation of G0 to G1 transition
Molecular Function
- protein binding
- enzyme binding
- protein domain specific binding
- identical protein binding
- histone methyltransferase binding
Cellular Component
- chromosome, centromeric region
- condensed chromosome, centromeric region
- nuclear chromosome, telomeric region
- chromatin
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000337620
- Coding exons
- 5
- Length
- 12195
- 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 | 1.93 | 37 | 87.9 | 0.421 | 0.00000403 | 1198 |
| Missense (PolyPhen) | 6 | 18.464 | 0.32496 | 306 | ||
| Synonymous | -1.52 | 40 | 29.5 | 1.36 | 0.00000149 | 301 |
| Loss of Function | 2.24 | 2 | 9.43 | 0.212 | 4.58e-7 | 131 |
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: Seems to be involved in transcriptional silencing in heterochromatin-like complexes. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. May contribute to the association of the heterochromatin with the inner nuclear membrane through its interaction with lamin B receptor (LBR). Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins. Contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation, mediates the recruitment of the methyltransferases SUV39H1 and/or SUV39H2 by the PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1. Mediates the recruitement of NIPBL to sites of DNA damage at double-strand breaks (DSBs) (PubMed:28167679). {ECO:0000250|UniProtKB:P23198, ECO:0000269|PubMed:28167679}.;
Recessive Scores
- pRec
- 0.207
Intolerance Scores
- LoFtool
- 0.337
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |