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POLR1C
RNA polymerase I and III subunit C
The POLR1C gene provides instructions for a protein subunit essential for two key enzymes, RNA polymerase I and RNA polymerase III, which are vital for producing different types of RNA in cells. POLR1C plays a crucial role in cellular function by contributing to the synthesis of ribosomal RNA (rRNA) and transfer RNA (tRNA), which are fundamental for protein assembly.
POLR1C is located on the short (p) arm of chromosome 6, at band 6p21.1. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The POLR1C gene encodes a component of RNA polymerase I and RNA polymerase III, two enzymes critical for gene expression. These enzymes are responsible for synthesising various forms of ribonucleic acid (RNA), including ribosomal RNA (rRNA) and transfer RNA (tRNA).
Proper function of POLR1C is essential for cellular survival and normal development, particularly for structures that form the bones and tissues of the face.
What the gene does
The POLR1C gene produces a subunit that is part of both RNA polymerase I and RNA polymerase III enzymes. These enzymes are fundamental to the process of RNA synthesis, which is a key step in gene expression where genetic information from DNA is transcribed into RNA.
RNA polymerase I primarily synthesises ribosomal RNA (rRNA), which forms a major component of ribosomes - the cellular machinery responsible for protein production. RNA polymerase III is involved in synthesising several types of RNA, including transfer RNA (tRNA), which transports amino acids to ribosomes for protein assembly, and a portion of rRNA. Therefore, the POLR1C protein is indirectly involved in the creation of all proteins within a cell, making it vital for overall cellular function and survival.
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Chromosome location
The POLR1C gene is situated on chromosome 6, specifically at position 6p21.1. This location refers to the short (p) arm of chromosome 6, within region 2, band 1, sub-band 1. The gene's precise location helps in understanding its genetic neighbourhood and potential interactions with other genes.
Protein structure
The POLR1C protein consists of 346 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic changes, known as variants, in the POLR1C gene can alter the protein's structure and function. These variants can affect the efficiency of RNA polymerase I and III, leading to a reduced production of essential RNA molecules. The impact of such variants can vary, from subtle cellular changes to significant developmental effects.
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.208dup | p.Ala70fs | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 11 |
c.229C>T | p.Arg77Ter | Pathogenic | ★★☆☆ | not provided |
c.232C>T | p.Arg78Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Treacher Collins syndrome 3 |
c.313A>T | p.Ile105Phe | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 11 |
c.325C>T | p.Arg109Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 11 |
c.616del | p.Gln206fs | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 11 |
c.699C>G | p.Tyr233Ter | Pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 11 |
c.785T>C | p.Ile262Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Leukodystrophy, hypomyelinating, 11 |
c.88C>T | p.Pro30Ser | Pathogenic/Likely pathogenic | ★★☆☆ | POLR1C-related disorder |
c.916_920del | p.Tyr306fs | Pathogenic/Likely pathogenic | ★★☆☆ | Treacher Collins syndrome 3 |
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 POLR1C gene have been identified in individuals with Treacher Collins syndrome, a condition characterised by abnormalities in the development of facial bones and tissues. The gene's involvement in this syndrome highlights its critical role in early facial development. Coloboma, a condition affecting eye structure, is also associated with POLR1C.
No disease links recorded for this gene in our reference set.
UK clinical status
The POLR1C gene is included in several NHS England Genomic Medicine Service national genomic test directories, indicating its clinical relevance in the UK. It is listed as 'green' on PanelApp for conditions such as Clefting, DDG2P, Deafness and congenital structural abnormalities, Foetal anomalies (R21), Inherited white matter disorders, Intellectual disability, Skeletal dysplasia (R104), and White matter disorders and cerebral calcification - childhood onset. A 'green' rating means there is sufficient evidence for routine panel inclusion.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the POLR1C gene?
The POLR1C gene provides instructions for making a subunit of RNA polymerase I and RNA polymerase III. These enzymes are crucial for synthesising ribosomal RNA (rRNA) and transfer RNA (tRNA), which are essential for protein production within cells.
Which condition is primarily associated with variants in POLR1C?
Variants in the POLR1C gene are primarily associated with Treacher Collins syndrome. This condition affects the development of bones and other tissues in the face.
How do POLR1C variants affect cellular function?
Variants in POLR1C can alter the structure and function of the POLR1C protein, leading to reduced activity of RNA polymerase I and III. This can decrease the production of essential RNA molecules, thereby impacting the cell's ability to create proteins effectively.
References
- Dauwerse JG, Dixon J, Seland S. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nature genetics. 2011. PMID: 21131976
- Fisher E. Exploring the genetic origins of Treacher Collins syndrome. Clinical genetics. 2011. PMID: 21261602
- Mao M, Fu G, Wu JS. Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning. Proceedings of the National Academy of Sciences of the United States of America. 1998. PMID: 9653160
- Adam MP, Bick S, Mirzaa GM. Treacher Collins Syndrome. 1993. PMID: 20301704