SETDB2
Chr 13SET domain bifurcated histone lysine methyltransferase 2
Also known as: C13orf4, CLLD8, CLLL8, KMT1F
This protein functions as a histone methyltransferase that specifically trimethylates histone H3 at lysine 9 (H3K9me3), contributing to transcriptional repression and playing critical roles in left-right axis specification during early development and chromosome segregation during mitosis. Mutations in SETDB2 cause neurodevelopmental disorders with intellectual disability and congenital anomalies, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.59), indicating that complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
173 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 59 | 0 | 59 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 68 | 9 | 0 | 77 |
Likely Benign | 0 | 3 | 1 | 1 | 5 |
Benign | 0 | 2 | 1 | 1 | 4 |
| Total | 0 | 73 | 72 | 2 | 147 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SETDB2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools