SETD4
protein-codingSET domain containing 4, the group of SET domain containing
Gene summary
Enables histone H4K20 methyltransferase activity. Predicted to be involved in several processes, including positive regulation of inflammatory response; regulation of cell proliferation in bone marrow; and regulation of gene expression. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Jun 2026]
- C21orf27
- C21orf18
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.8 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 SETD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017438.5. 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 | 54 | 7 | 61 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 59 | 7 | 0 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059134.1 | 10 | MANE Select | |
| Ensembl | ENSP00000329189.4 | 10 | MANE Select | |
| RefSeq | NP_001007260.1 | 6 | Standard | |
| RefSeq | NP_001007262.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Histone Modifications
- Metabolism of lipids
- Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
- Prostaglandin Leukotriene metabolism
- Arachidonic acid metabolism
Biological Process
- peptidyl-lysine trimethylation
- peptidyl-lysine monomethylation
Molecular Function
- protein-lysine N-methyltransferase activity
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000399215
- Coding exons
- 10
- Length
- 44849
- Individuals with no LoFs
- 125589
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 159
- Defined
- 125748
- p
- 0.000632
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.344 | 221 | 236 | 0.937 | 0.0000130 | 2843 |
| Missense (PolyPhen) | 63 | 70.287 | 0.89633 | 862 | ||
| Synonymous | 0.759 | 88 | 97.5 | 0.902 | 0.00000624 | 848 |
| Loss of Function | 0.616 | 21 | 24.3 | 0.865 | 0.00000128 | 283 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00074 | 0.00072 | rare |
| Ashkenazi Jewish | 0.0038 | 0.0038 | notable |
| East Asian | 0.00065 | 0.00054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00035 | 0.00035 | rare |
| South Asian | 0.0010 | 0.0010 | notable |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0996
Intolerance Scores
- LoFtool
- 0.742
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.520
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |