SMYD2
protein-codingSET and MYND domain containing 2, the group of SET domain containing|Zinc fingers MYND-type|Lysine methyltransferases
Gene summary
SET domain-containing proteins, such as SMYD2, catalyze lysine methylation (Brown et al., 2006 [PubMed 16805913]).[supplied by OMIM, Nov 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.0 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 SMYD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020197.3. 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 | 62 | 1 | 63 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 70 | 1 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064582.2 | 12 | MANE Select | |
| Ensembl | ENSP00000355924.5 | 12 | MANE Select | |
| Ensembl | ENSP00000409822.2 | 3 | Standard | |
| Ensembl | ENSP00000543679.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| smyd2a | Danio rerio | Structure: skeletal muscle cell Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Histone Modifications
- Gene expression (Transcription)
- Generic Transcription Pathway
- PKMTs methylate histone lysines
- RNA Polymerase II Transcription
Biological Process
- negative regulation of transcription by RNA polymerase II
- heart development
- negative regulation of cell population proliferation
- histone H3-K36 methylation
- peptidyl-lysine monomethylation
Molecular Function
- RNA polymerase II complex binding
- p53 binding
- protein binding
- lysine N-methyltransferase activity
- protein-lysine N-methyltransferase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366957
- Coding exons
- 12
- Length
- 56030
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125748
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.28 | 179 | 234 | 0.765 | 0.0000120 | 2870 |
| Missense (PolyPhen) | 52 | 76.406 | 0.68057 | 960 | ||
| Synonymous | -0.311 | 93 | 89.3 | 1.04 | 0.00000501 | 760 |
| Loss of Function | 2.14 | 13 | 24.4 | 0.533 | 0.00000121 | 305 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'. {ECO:0000269|PubMed:17108971, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:21782458, ECO:0000269|PubMed:21880715}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.369
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |