SETD1B

Chr 12AD

SET domain containing 1B, histone lysine methyltransferase

Also known as: IDDSELD, KMT2G, Set1B

NCBI Gene: 23067 ENSG00000139718 UniProt: Q9UPS6 OMIM: 611055

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

SET1B is a component of a histone methyltransferase complex that produces trimethylated histone H3 at Lys4 (Lee et al., 2007 [PubMed 17355966]).[supplied by OMIM, Mar 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with seizures and language delayMIM #619000

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — SETD1B