RNF40

Chr 16

ring finger protein 40

Also known as: BRE1B, RBP95, STARING

NCBI Gene: 9810 ENSG00000103549 UniProt: O75150 OMIM: 607700

RNF40 encodes an E3 ubiquitin ligase that forms a complex with RNF20 to monoubiquitinate histone H2B, which is essential for transcriptional activation and proper histone methylation patterns. Mutations cause an autosomal dominant neurodevelopmental disorder with intellectual disability, developmental delay, and distinctive facial features. This gene is highly constrained against loss-of-function variants, reflecting its critical role in epigenetic regulation.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a RING finger, a motif known to be involved in protein-protein and protein-DNA interactions. This protein was reported to interact with the tumor suppressor protein RB1. Studies of the rat counterpart suggested that this protein may function as an E3 ubiquitin-protein ligase, and facilitate the ubiquitination and degradation of syntaxin 1, which is an essential component of the neurotransmitter release machinery. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · ADLimitednot for standalone diagnostic reporting

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.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· predicted