SETDB2

Chr 13

SET domain bifurcated histone lysine methyltransferase 2

Also known as: C13orf4, CLLD8, CLLL8, KMT1F

NCBI Gene: 83852 ENSG00000136169 UniProt: Q96T68 OMIM: 607865

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.59

LOEUF

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Mechanism