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POLR3B
RNA polymerase III subunit B
The POLR3B gene provides instructions for a key component of RNA polymerase III, an enzyme crucial for generating various RNA molecules essential for cellular function. POLR3B codes for a subunit of RNA polymerase III, an enzyme that synthesises RNA from DNA templates.
POLR3B is located on the long (q) arm of chromosome 12, at band 12q23.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The POLR3B gene, also known as RNA polymerase III subunit B, plays a critical role in cellular function by providing instructions for one of the subunits of RNA polymerase III. This enzyme is indispensable for synthesising various types of RNA, which are vital for the normal operation and survival of cells.
Inheritance patterns associated with conditions linked to POLR3B variants can vary.
What the gene does
The POLR3B gene directs the production of a subunit of RNA polymerase III, an enzyme fundamentally involved in the process of transcription. During transcription, RNA polymerase III binds to DNA and uses it as a template to synthesise RNA molecules. This enzyme is particularly important for producing ribosomal RNA (rRNA) and transfer RNA (tRNA).
Both rRNA and tRNA are essential components of the protein synthesis machinery. Ribosomal RNA forms part of ribosomes, where proteins are assembled, while transfer RNA molecules transport specific amino acids to the ribosome for incorporation into proteins. The proper functioning of RNA polymerase III, therefore, directly impacts protein production, which is crucial for cellular health and survival.
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Chromosome location
The POLR3B gene is located on chromosome 12 at position 12q23.3. This specific location indicates its address within the human genome, residing on the long arm of chromosome 12.
Protein structure
The POLR3B protein consists of 1133 amino acids. It contains a C4-type (Zinc finger) domain, which is located between amino acid positions 1080 and 1095.
Key variants
Genetic variations within the POLR3B gene can influence its function, potentially affecting the production and activity of RNA polymerase III. These variants may alter the gene's instructions, leading to a range of health outcomes.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1263+2T>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Hypogonadotropic hypogonadism 7 with or without anosmia |
c.1568T>A | p.Val523Glu | Pathogenic/Likely pathogenic | ★★☆☆ | Hypogonadotropic hypogonadism 7 with or without anosmia |
c.2084-6A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | POLR3B-related disorder |
c.2104C>T | p.Arg702Ter | Pathogenic/Likely pathogenic | ★★☆☆ | POLR3B-related disorder |
c.2376del | p.Met794fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.2413C>T | p.Arg805Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism |
c.2570+1G>A | - | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism |
c.2809C>T | p.Arg937Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism |
c.361C>T | p.Arg121Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.664C>T | p.Arg222Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the POLR3B gene are associated with several inherited conditions. One notable condition is Pol III-related leukodystrophy, an autosomal recessive disorder characterised by abnormalities in the brain's white matter. This condition is typically linked to a reduced ability to form myelin, which is crucial for insulating nerve fibres and enabling rapid nerve impulse transmission.
- Pol III-related leukodystrophy (4H) Dedicated page coming soon
UK clinical status
The POLR3B gene is included in several UK NHS national genomic testing panels. It is listed as 'green' on PanelApp for conditions such as Ataxia and cerebellar anomalies - childhood onset, Inherited white matter disorders, and Leukodystrophy, adult onset (R62). It also features on panels for DDG2P, Foetal anomalies (R21), Hereditary neuropathy or pain disorder (R78), and Intellectual disability, as well as White matter disorders and cerebral calcification - childhood onset.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the POLR3B gene?
The POLR3B gene provides instructions for a subunit of RNA polymerase III, an enzyme critical for synthesising various RNA molecules, including ribosomal RNA (rRNA) and transfer RNA (tRNA). These RNAs are essential for building proteins and maintaining normal cellular function.
Which conditions are associated with variants in the POLR3B gene?
Variants in the POLR3B gene are primarily associated with Pol III-related leukodystrophy. This condition involves abnormalities in the brain's white matter, often due to a reduced capacity to form myelin, which is vital for nerve signal transmission.
How does the POLR3B gene relate to white matter disorders?
The POLR3B gene's role in RNA synthesis impacts cellular processes, including those critical for myelin formation in the brain. Dysfunction due to POLR3B variants can lead to hypomyelination, a key feature of white matter disorders like Pol III-related leukodystrophy, affecting nerve impulse transmission.
References
- Vanderver A, Tonduti D, Bernard G. More than hypomyelination in Pol-III disorder. Journal of neuropathology and experimental neurology. 2013. PMID: 23242285
- Daoud H, Tétreault M, Gibson W. Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism. Journal of medical genetics. 2013. PMID: 23355746
- Saitsu H, Osaka H, Sasaki M. Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. American journal of human genetics. 2011. PMID: 22036171
- Tétreault M, Choquet K, Orcesi S. Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. American journal of human genetics. 2011. PMID: 22036172