KDM4B

Chr 19

lysine demethylase 4B

Also known as: JMJD2B, MRD65, TDRD14B

NCBI Gene: 23030 ENSG00000127663 UniProt: O94953

The protein functions as a histone demethylase that removes methyl groups from H3K36 and H3K9me2/H3K9me3, regulating chromatin structure and gene expression during brain development. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder 65. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely mechanism of pathogenicity.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Enables histone H3K36 demethylase activity and histone H3K9me2/H3K9me3 demethylase activity. Predicted to be involved in brain development; chromatin remodeling; and regulation of gene expression. Located in cytosol and nucleoplasm. Implicated in autosomal dominant intellectual developmental disorder 65; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 65

Clinical highlights

Gene-disease validity (ClinGen)

intellectual developmental disorder, autosomal dominant 65 · ADStrongappropriate for clinical testing

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

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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