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CAVIN1
caveolae associated protein 1
The CAVIN1 gene provides instructions for producing the cavin-1 protein, which is crucial for the formation and stability of caveolae, small indentations on cell membranes involved in various cellular processes. The cavin-1 protein is found in many cell types, including bone-building cells, muscle cells, and fat cells.
CAVIN1 is located on the long (q) arm of chromosome 17, at band 17q21.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The CAVIN1 gene, also known as caveolae associated protein 1, encodes the cavin-1 protein, which is integral to cellular function across the human body. This protein is particularly abundant in osteoblasts (bone-forming cells), muscle cells, and adipocytes (fat-storing cells), where it contributes to vital physiological processes. Research suggests cavin-1 is essential for forming and stabilising caveolae, which are small pockets on the cell membrane involved in molecular transport and cell signalling.
What the gene does
The cavin-1 protein, encoded by the CAVIN1 gene, is crucial for the structural integrity and function of caveolae, which are small invaginations of the cell membrane. These structures are involved in a range of cellular activities, including endocytosis (the transport of molecules into the cell), maintaining cell structure, and regulating chemical signalling pathways. Caveolae are especially prevalent in adipocytes, where they are believed to be vital for the normal processing, transport, and storage of fats. Beyond its role in caveolae, cavin-1 is also implicated in repairing damage to the outer cell membrane, regulating cell growth and division (proliferation), cell movement, and cell senescence. Its specific functions may vary depending on the cell type and its location within the cell, including in the nucleus and cytoplasm.
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Chromosome location
The CAVIN1 gene is situated on chromosome 17 at position 17q21.2. This genomic location specifies its precise address within the human genome, helping to identify its placement relative to other genes on chromosome 17.
Protein structure
The cavin-1 protein, which is 390 amino acids in length, features several distinct structural elements. The region spanning amino acids 1-98 is required for homotrimerization and for interaction with CAVIN2 and CAVIN3. This region also contains a disordered segment (amino acids 1-40) and a nuclear export signal (amino acids 52-62). Two leucine-zipper motifs are present: Leucine-zipper 1 (amino acids 53-75) and Leucine-zipper 2 (amino acids 166-186). Further structural components include a nuclear localization signal (amino acids 136-152), another disordered region (amino acids 172-201), and a coiled-coil domain (amino acids 199-282). A second nuclear localization signal is found between amino acids 233-249, followed by Leucine-zipper 3 (amino acids 257-297). The protein concludes with a final disordered region from amino acids 344-366.
Key variants
Variants within the CAVIN1 gene can alter the function of the cavin-1 protein. These genetic changes can range from small alterations in the DNA sequence to larger structural rearrangements. Understanding these variants is important for elucidating their potential impact on protein function and associated health implications.
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.518_521del | p.Lys173fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital generalized lipodystrophy type 4 |
c.141_148del | p.Asp47fs | Pathogenic | ★☆☆☆ | Congenital generalized lipodystrophy |
c.462del | p.Met154fs | Pathogenic | ★☆☆☆ | not provided |
c.696dup | p.Lys233fs | Pathogenic | ★☆☆☆ | Congenital generalized lipodystrophy type 4 |
c.135del | p.Lys45fs | Pathogenic | - | Congenital generalized lipodystrophy type 4 |
c.160del | p.Val54fs | Pathogenic | - | Congenital generalized lipodystrophy type 4 |
c.259C>T | p.Gln87Ter | Pathogenic | - | Congenital generalized lipodystrophy type 4 |
c.362dup | p.Lys122fs | Pathogenic | - | Congenital generalized lipodystrophy type 4 |
c.471+1G>T | - | Pathogenic | - | Congenital generalized lipodystrophy type 4 |
c.478_481dup | p.Lys161fs | Pathogenic | - | Congenital generalized lipodystrophy type 4 |
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
Pathogenic variants in the CAVIN1 gene are associated with inherited conditions that primarily affect fat metabolism and distribution. Specifically, mutations in CAVIN1 have been identified as a cause of congenital generalized lipodystrophy type 4, a rare disorder characterised by an almost complete absence of adipose tissue and a distinct muscular appearance. This shortage of fat tissue can lead to several health complications, including high levels of triglycerides.
No disease links recorded for this gene in our reference set.
UK clinical status
In the UK, the CAVIN1 gene is included in several NHS Genomic Medicine Service national test directories via PanelApp. It is listed as 'green' for Congenital muscular dystrophy (R79), Insulin resistance (including lipodystrophy), and Severe insulin resistance and lipodystrophy syndromes (R158), indicating strong evidence for its association with these conditions for diagnostic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the CAVIN1 gene?
The CAVIN1 gene provides instructions for the cavin-1 protein, which is essential for the formation and stability of caveolae. These are small membrane invaginations involved in molecular transport, maintaining cell structure, and regulating cell signalling pathways.
Which conditions are associated with CAVIN1 gene variants?
Variants in the CAVIN1 gene are primarily associated with congenital generalized lipodystrophy type 4. This rare condition is characterised by a significant reduction in adipose (fat) tissue, which can lead to various health problems.
Where is the CAVIN1 gene located in the human genome?
The CAVIN1 gene is located on chromosome 17 at position 17q21.2. This specifies its precise chromosomal address within the human genome.
References
- Low JY, Nicholson HD. Emerging role of polymerase-1 and transcript release factor (PTRF/ Cavin-1) in health and disease. Cell and tissue research. 2014. PMID: 25107607
- Rajab A, Straub V, McCann LJ. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS genetics. 2010. PMID: 20300641
- Shastry S, Delgado MR, Dirik E. Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. American journal of medical genetics. Part A. 2010. PMID: 20684003
- Hayashi YK, Matsuda C, Ogawa M. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. The Journal of clinical investigation. 2009. PMID: 19726876
- Liu L, Pilch PF. A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization. The Journal of biological chemistry. 2008. PMID: 18056712
- Hill MM, Bastiani M, Luetterforst R. PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell. 2008. PMID: 18191225