KDM6B

Chr 17

lysine demethylase 6B

Also known as: JMJD3, NEDCFSA, NEDSST

NCBI Gene: 23135 ENSG00000132510 UniProt: O15054

This histone demethylase specifically removes methyl groups from lysine 27 of histone H3, playing a central role in gene expression regulation and chromatin remodeling during development. Mutations cause Stolerman neurodevelopmental syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating critical developmental importance.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtStolerman neurodevelopmental syndrome

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

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

123

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)