POLR1A

Chr 2

RNA polymerase I subunit A

Also known as: A190, AFDCIN, HLD27, RPA1, RPA190, RPA194, RPO1-4, RPO14

NCBI Gene: 25885 ENSG00000068654 UniProt: O95602

POLR1A encodes the largest catalytic subunit of RNA polymerase I, which transcribes DNA into ribosomal RNA precursors essential for ribosome biogenesis. Mutations cause acrofacial dysostosis Cincinnati type and hypomyelinating leukodystrophy, with both autosomal dominant and autosomal recessive inheritance patterns reported. This gene is highly constrained against loss-of-function variants in the general population, indicating that POLR1A variants are likely to be pathogenic when they do occur.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is the largest subunit of the RNA polymerase I complex. The encoded protein represents the catalytic subunit of the complex, which transcribes DNA into ribosomal RNA precursors. Defects in this gene are a cause of the Cincinnati type of acrofacial dysostosis. [provided by RefSeq, May 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAcrofacial dysostosis, Cincinnati type

UniProtLeukodystrophy, hypomyelinating, 27

Clinical highlights

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

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P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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