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LRPPRC
leucine rich pentatricopeptide repeat containing
LRPPRC is located on the short (p) arm of chromosome 2, at band 2p21. Arm ratio per GRCh38 - banding schematic.
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Overview
LRPPRC (leucine rich pentatricopeptide repeat containing) is located on chromosome 2 at position 2p21. The gene encodes a protein that functions primarily within mitochondria, where it participates in post-transcriptional regulation of mitochondrial gene expression. Mitochondria contain their own small genome encoding essential components of the respiratory chain, the molecular machinery responsible for generating adenosine triphosphate (ATP), the cell's primary energy currency.
The LRPPRC protein helps stabilise specific mitochondrial messenger RNA molecules and coordinates their translation into functional proteins. Disruption of LRPPRC function can impair mitochondrial protein synthesis, leading to deficiencies in respiratory chain complexes and reduced cellular energy production. This gene is particularly important for understanding rare mitochondrial disorders that affect energy metabolism.
What the gene does
The LRPPRC protein operates within the mitochondrial matrix, where it binds to mitochondrial messenger RNA molecules and regulates their stability and translation. The protein contains multiple pentatricopeptide repeat motifs, structural elements commonly found in RNA-binding proteins across various organisms. These repeats enable LRPPRC to recognise and interact with specific RNA sequences.
LRPPRC works in concert with other mitochondrial RNA-binding proteins to form ribonucleoprotein complexes that protect messenger RNA from degradation and facilitate their translation by mitochondrial ribosomes. The protein shows particular importance for the stability of COX1 messenger RNA, which encodes a core subunit of cytochrome c oxidase (complex IV of the respiratory chain). By maintaining appropriate levels of mitochondrial transcripts, LRPPRC ensures that cells can produce sufficient quantities of respiratory chain components to meet their energy demands.
Cellular energy production depends on the coordinated assembly and function of five multi-subunit enzyme complexes in the inner mitochondrial membrane. LRPPRC contributes to this process by ensuring that mitochondrially encoded subunits are synthesised at appropriate rates to match nuclear-encoded components imported from the cytoplasm.
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Chromosome location
LRPPRC is located on the short arm of chromosome 2 at cytogenetic band 2p21. The gene spans a region of genomic DNA that contains multiple exons encoding the full-length protein transcript. The chromosomal location places LRPPRC among other genes with diverse cellular functions, though no functionally related gene cluster has been identified at this locus.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. The LRPPRC protein contains stretches of leucine-rich pentatricopeptide repeat motifs, which are predicted to form helical structures that create an RNA-binding surface. These repeats typically consist of degenerate 35-amino-acid sequences arranged in tandem arrays. The protein also contains regions predicted to function as mitochondrial targeting sequences that direct the newly synthesised protein from the cytoplasm into mitochondria.
Key variants
Genetic variants in LRPPRC range from single nucleotide changes to larger deletions affecting one or more exons. Pathogenic variants typically disrupt the protein's RNA-binding capacity or impair its stability within mitochondria. The functional consequences of LRPPRC variants can be assessed through biochemical studies measuring respiratory chain enzyme activities and mitochondrial protein synthesis rates in patient-derived cells. Variant interpretation requires careful consideration of biochemical data alongside genetic evidence.
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.123del | p.Ala42fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.1474C>T | p.Arg492Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.2050C>T | p.Gln684Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.2072C>G | p.Ser691Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.2986_3001del | p.Leu996fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.3254_3255del | p.Gln1085fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.3310del | p.Asp1104fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.3663dup | p.Phe1222fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.3737_3740del | p.Asn1246fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
c.3900+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type |
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
Changes in LRPPRC have been associated with mitochondrial disorders characterised by impaired cellular energy production. These conditions typically present with multi-system involvement, reflecting the widespread cellular dependence on mitochondrial function. Clinical features may include neurological symptoms, developmental delay, and metabolic abnormalities. The severity and specific manifestations can vary depending on the nature of the genetic change and the degree of residual protein function. Diagnosis of LRPPRC-related conditions involves integration of clinical findings, biochemical testing, and genetic analysis.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the LRPPRC protein do in cells?
The LRPPRC protein works inside mitochondria to stabilise and regulate messenger RNA molecules that encode components of the cellular energy-production machinery. It binds to specific mitochondrial RNA sequences and protects them from degradation, ensuring that cells can synthesise adequate amounts of respiratory chain proteins.
Where is the LRPPRC gene located?
LRPPRC is located on the short arm of chromosome 2 at position 2p21. Each person typically inherits one copy of the gene from each parent.
How do changes in LRPPRC affect mitochondrial function?
Pathogenic variants in LRPPRC can reduce the stability of mitochondrial messenger RNA molecules, leading to decreased production of respiratory chain components. This impairs the mitochondria's ability to generate cellular energy efficiently, which can affect multiple organ systems that have high energy demands.