SETD1B

Chr 12AD

SET domain containing 1B, histone lysine methyltransferase

Also known as: IDDSELD, KMT2G, Set1B

SETD1B encodes a histone methyltransferase that catalyzes trimethylation of histone H3 at lysine 4 (H3K4me3), a chromatin modification essential for active gene transcription and DNA repair. Mutations cause autosomal dominant intellectual developmental disorder with seizures and language delay. The gene is highly constrained against loss-of-function variants (pLI = 1.0), reflecting its critical role in transcriptional regulation during development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.151 OMIM phenotype
Clinical SummarySETD1B
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SETD1B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 6.74
OE 0.07 (0.030.15)
Highly constrained

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

Missense Constraint
4.67Z-score
OE missense 0.61 (0.570.65)
706 obs / 1151.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.030.15)
00.351.4
Missense OE0.61 (0.570.65)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 4 / 60.6Missense obs/exp: 706 / 1151.5Syn Z: -1.06
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSETD1B-related intellectual disability, epilepsy and autismLOFAD
DN
0.2399th %ile
GOF
0.2696th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.15

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SETD1B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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