H3-3B

Chr 17AD

H3.3 histone B

Also known as: BRYLIB2, H3.3B, H3F3B

NCBI Gene: 3021 ENSG00000132475 UniProt: P84243 OMIM: 601058

The protein encoded by H3-3B is histone H3.3, a variant histone that replaces conventional H3 in nucleosomes of transcriptionally active genes and plays a central role in chromatin structure, transcription regulation, and chromosomal stability. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function mutations (pLI 0.81, LOEUF 0.55), reflecting its essential role in normal development.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene contains introns and its mRNA is polyadenylated, unlike most histone genes. The protein encoded by this gene is a replication-independent histone that is a member of the histone H3 family. Pseudogenes of this gene have been identified on the X chromosome, and on chromosomes 5, 13 and 17. [provided by RefSeq, Oct 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bryant-Li-Bhoj neurodevelopmental syndrome 2MIM #619721

UniProtGlioma

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.55

LOEUF

Mechanism· predicted

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GeneReview available — H3-3B

Authoritative clinical overview · Recommended first read