POLR2A

Chr 17AD

RNA polymerase II subunit A

Also known as: NEDHIB, POLR2, POLRA, RPB1, RPBh1, RPO2, RPOL2, RpIILS

NCBI Gene: 5430 ENSG00000181222 UniProt: P24928 OMIM: 180660

This gene encodes the largest subunit of RNA polymerase II, which synthesizes messenger RNA and many functional non-coding RNAs by catalyzing the formation of phosphodiester bonds during transcription. Mutations cause a neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.16), reflecting its essential role in transcription.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a carboxy terminal domain composed of heptapeptide repeats that are essential for polymerase activity. These repeats contain serine and threonine residues that are phosphorylated in actively transcribing RNA polymerase. In addition, this subunit, in combination with several other polymerase subunits, forms the DNA binding domain of the polymerase, a groove in which the DNA template is transcribed into RNA. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalitiesMIM #618603

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities · ADDefinitivesufficient evidence for diagnostic panels

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)

—

P/LP submissions

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P/LP missense

0.16

LOEUF· LoF intol.

Multiple*

Mechanism· predicted