KMT5B

Chr 11AD

lysine methyltransferase 5B

Also known as: CGI-85, CGI85, MRD51, SUV420H1

NCBI Gene: 51111 ENSG00000110066 UniProt: Q4FZB7 OMIM: 610881

The protein is a histone methyltransferase that specifically methylates lysine-20 of histone H4 to regulate transcriptional repression, heterochromatin formation, and DNA repair. Heterozygous loss-of-function mutations cause autosomal dominant intellectual developmental disorder through haploinsufficiency. The gene is highly intolerant to loss-of-function variants, consistent with dominant negative effects from reduced histone methylation activity.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that contains a SET domain. SET domains appear to be protein-protein interaction domains that mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). The function of this gene has not been determined. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 51MIM #617788

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)

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P/LP submissions

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P/LP missense

0.08

LOEUF· LoF intol.

LOF

Mechanism· G2P