SETD1A

Chr 16AD

SET domain containing 1A, histone lysine methyltransferase

Also known as: EPEDD, EPEO2, KMT2F, NEDSID, Set1, Set1A

NCBI Gene: 9739 ENSG00000099381 UniProt: O15047 OMIM: 611052

This protein is a histone methyltransferase that catalyzes mono-, di-, and trimethylation of histone H3 at lysine 4, a chromatin modification that marks transcription start sites of active genes. Loss-of-function mutations cause autosomal dominant early-onset epilepsy with or without developmental delay, and neurodevelopmental disorder with speech impairment and dysmorphic facies. The pathogenic mechanism involves haploinsufficiency disrupting normal gene transcription regulation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at Lys4. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to generally mark the transcription start sites of active genes. The protein contains SET domains, a RNA recognition motif domain and is a member of the class V-like SAM-binding methyltransferase superfamily. [provided by RefSeq, Dec 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 2, with or without developmental delayMIM #618832

Neurodevelopmental disorder with speech impairment and dysmorphic faciesMIM #619056

Clinical highlights

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)

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P/LP submissions

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P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P