SETDB1

Chr 1

SET domain bifurcated histone lysine methyltransferase 1

Also known as: ESET, H3-K9-HMTase4, KG1T, KMT1E, TDRD21

NCBI Gene: 9869ENSG00000143379UniProt: Q15047

This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]

GeneReviewsResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
138
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· predicted
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GeneReview available — SETDB1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.20LOEUF
pLI 1.000
Z-score 6.69
OE 0.11 (0.06–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
4.01Z-score
OE missense 0.59 (0.54–0.63)
434 obs / 741.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.11 (0.06–0.20)
0≤0.351.4
Missense OE?0.59 (0.54–0.63)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 7 / 65.4Missense obs/exp: 434 / 741.0Syn Z: -0.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SETDB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients