POLR3B

Chr 12ADAR

RNA polymerase III subunit B

Also known as: C128, CMT1I, HLD8, INMAP, RPC2

NCBI Gene: 55703 ENSG00000013503 UniProt: Q9NW08 OMIM: 614366

This gene encodes the second largest subunit of RNA polymerase III, which synthesizes transfer RNAs and small ribosomal RNAs and forms part of the enzyme's catalytic center. Mutations cause hypomyelinating leukodystrophy type 8 (with or without oligodontia and hypogonadism) and demyelinating Charcot-Marie-Tooth disease type 1I through both autosomal recessive and autosomal dominant inheritance patterns. The gene shows tolerance to loss-of-function variants, suggesting mutations can cause disease through multiple mechanisms depending on the specific variant type.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the second largest subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The largest subunit and the encoded protein form the catalytic center of RNA polymerase III. Mutations in this gene are a cause of hypomyelinating leukodystrophy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, demyelinating, type 1IMIM #619742

Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadismMIM #614381

Clinical highlights

Gene-disease validity (ClinGen)

POLR3B-related disorder · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

0.87

LOEUF

LOF

Mechanism· G2P

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GeneReview available — POLR3B