SETDB2

Chr 13

SET 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.

Summary from RefSeq, UniProt
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0
Active trials
12
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.59
LOEUF
Mechanism
Clinical SummarySETDB2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.58
OE 0.38 (0.260.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.75Z-score
OE missense 0.74 (0.670.82)
265 obs / 358.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.260.59)
00.351.4
Missense OE0.74 (0.670.82)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 15 / 39.2Missense obs/exp: 265 / 358.2Syn Z: -0.26

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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