SMYD1
protein-codingSET and MYND domain containing 1, the group of Zinc fingers MYND-type|SET domain containing|Lysine methyltransferases
Gene summary
Predicted to enable histone H3K4 methyltransferase activity. Involved in positive regulation of myoblast differentiation and positive regulation of myotube differentiation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005045
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SMYD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198274.4. 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 | 2 | 3 | |||
| missense | 99 | 2 | 1 | 102 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 99 | 3 | 3 | 105 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_938015.1 | 10 | MANE Select | |
| Ensembl | ENSP00000393453.2 | 10 | MANE Select | |
| RefSeq | NP_001317293.1 | 9 | Standard | |
| Ensembl | ENSP00000387482.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| smyd1b | Danio rerio | Structure: cardiac muscle cell Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Heart Development
- Histone Modifications
Biological Process
- chromatin remodeling
- heart development
- positive regulation of myotube differentiation
- histone lysine methylation
- skeletal muscle cell differentiation
Molecular Function
- DNA binding
- transcription corepressor activity
- protein binding
- histone-lysine N-methyltransferase activity
- metal ion binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000419482
- Coding exons
- 10
- Length
- 45608
- Individuals with no LoFs
- 125666
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 82
- Defined
- 125748
- p
- 0.000326
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.250 | 310 | 298 | 1.04 | 0.0000178 | 3268 |
| Missense (PolyPhen) | 90 | 93.897 | 0.9585 | 977 | ||
| Synonymous | -1.88 | 142 | 116 | 1.22 | 0.00000762 | 866 |
| Loss of Function | 1.66 | 14 | 22.5 | 0.622 | 9.55e-7 | 283 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00090 | 0.00090 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0010 | 0.0010 | notable |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Methylates histone H3 at 'Lys-4' (H3K4me), seems able to perform both mono-, di-, and trimethylation. Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis.;
Recessive Scores
- pRec
- 0.0934
Intolerance Scores
- LoFtool
- 0.408
- RVIS EVS
- -0.2
- RVIS percentile EVS
- 39.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.198
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |