SETDB2
protein-codingSET domain bifurcated histone lysine methyltransferase 2, the group of Lysine methyltransferases|Methyl-CpG binding domain containing|SET domain containing
Gene summary
This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
- C13orf4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~50.7 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 SETDB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001160308.3. 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 | 1 | 1 | 1 | 3 | ||
| missense | 73 | 3 | 2 | 78 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 81 | 4 | 3 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001153780.1 | 13 | MANE Select | |
| Ensembl | ENSP00000482240.2 | 13 | MANE Select | |
| RefSeq | NP_001307628.1 | 13 | Standard | |
| RefSeq | NP_001380904.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| setdb2 | Danio rerio | Structure: hindbrain neural keel Quality: increased width abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Lysine degradation - Homo sapiens (human)
- Histone Modifications
- PKMTs methylate histone lysines
- Chromatin modifying enzymes
- Lysine metabolism
Biological Process
- mitotic cell cycle
- heart looping
- chromosome segregation
- negative regulation of transcription, DNA-templated
- cell division
Molecular Function
- DNA binding
- protein binding
- zinc ion binding
- histone-lysine N-methyltransferase activity
- histone methyltransferase activity (H3-K9 specific)
Cellular Component
- nucleus
- nucleoplasm
- chromosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000317257
- Coding exons
- 14
- Length
- 50710
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125746
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.75 | 265 | 358 | 0.740 | 0.0000170 | 4751 |
| Missense (PolyPhen) | 73 | 140.18 | 0.52075 | 1864 | ||
| Synonymous | -0.258 | 133 | 129 | 1.03 | 0.00000623 | 1295 |
| Loss of Function | 3.58 | 15 | 39.2 | 0.383 | 0.00000225 | 478 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Histone methyltransferase involved in left-right axis specification in early development and mitosis. Specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 is a specific tag for epigenetic transcriptional repression that recruits HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Contributes to H3K9me3 in both the interspersed repetitive elements and centromere-associated repeats. Plays a role in chromosome condensation and segregation during mitosis. {ECO:0000269|PubMed:20404330}.;
Recessive Scores
- pRec
- 0.0923
Intolerance Scores
- LoFtool
- 0.0881
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.523
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |