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PCNT
pericentrin
The PCNT gene provides instructions for pericentrin, a protein vital for cell division and the proper functioning of centrosomes, cellular structures involved in organising microtubules. The PCNT gene encodes pericentrin, a protein that plays a critical role in cellular processes such as cell division and the assembly of microtubules within cells.
PCNT is located on the long (q) arm of chromosome 21, at band 21q22.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The PCNT gene is responsible for producing the pericentrin protein, which is an important component of centrosomes. Centrosomes are cellular structures that are essential for orchestrating cell division and maintaining cellular organisation through their role in microtubule assembly. Understanding the PCNT gene and its protein product is key to comprehending several developmental conditions.
What the gene does
The pericentrin protein, encoded by the PCNT gene, is primarily located within centrosomes, which are cellular organelles that act as the main microtubule-organising centres in animal cells. Pericentrin functions as an anchoring protein, securing other vital proteins to the centrosome. This anchoring role is crucial for the proper assembly of microtubules, which are filament-like structures that help cells maintain their shape, transport materials internally, and facilitate cell division. By interacting with these proteins, pericentrin helps regulate the cell cycle, ensuring cells divide in an organised, step-by-step manner. Disruptions to this process can have significant consequences for cellular function and organism development.
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Chromosome location
The PCNT gene is situated on chromosome 21 at position 21q22.3. This specific genomic location provides the cellular machinery with the instructions to produce the pericentrin protein. The precise positioning of the gene is important for its regulation and expression within the human genome.
Protein structure
The pericentrin protein, measuring 3336 amino acids in length, exhibits a complex domain architecture. It features several regions of coiled-coil domains, including segments from amino acids 258-553, 675-835, 1010-1146, 1299-1949, 2064-2082, and 2536-3086. Interspersed within these are multiple disordered regions, such as amino acids 1-71, 81-100, 569-589, 1619-1638, 1954-1974, 2168-2214, 2318-2374, and 2875-2910. A specific region from amino acids 2983-3246 is noted for its interaction with NEK2, highlighting a key functional area.
Key variants
Variants in the PCNT gene can alter the structure or function of the pericentrin protein. These changes can range from single base pair alterations to larger deletions or duplications. Pathogenic variants are associated with a spectrum of conditions, often impacting cellular processes like cell division and microtubule organisation. The inheritance pattern for conditions linked to PCNT is typically autosomal recessive.
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.1164_1165del | p.Arg388fs | Pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
c.3424_3425del | p.Ser1142fs | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
c.3863_3866del | p.His1288fs | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.4522C>T | p.Gln1508Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
c.4998del | p.Gly1667fs | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
c.5056C>T | p.Gln1686Ter | Pathogenic/Likely pathogenic | ★★☆☆ | PCNT-related disorder |
c.5188C>T | p.Arg1730Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
c.6039_6040del | p.Cys2014fs | Pathogenic/Likely pathogenic | ★★☆☆ | PCNT-related disorder |
c.6205C>T | p.Gln2069Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
c.7448dup | p.His2484fs | Pathogenic/Likely pathogenic | ★★☆☆ | Microcephalic osteodysplastic primordial dwarfism type II |
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 PCNT gene are primarily associated with microcephalic osteodysplastic primordial dwarfism type II (MOPDII). This condition is characterised by severe short stature, a small head circumference (microcephaly), and skeletal abnormalities. Changes in PCNT can lead to an abnormally short or non-functional pericentrin protein, impairing centrosome function and disrupting cell division, which contributes to the developmental features observed in MOPDII.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PCNT variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The PCNT gene is recognised within the UK's NHS Genomic Medicine Service, appearing on several Green RAG status panels in PanelApp. These include DDG2P, Foetal anomalies (R21), Insulin resistance (including lipodystrophy), Intellectual disability, IUGR and IGF abnormalities, Limb disorders, Severe insulin resistance and lipodystrophy syndromes (R158), Severe microcephaly (R88), and Skeletal dysplasia (R104).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the PCNT gene?
The PCNT gene provides instructions for making the pericentrin protein, which is crucial for the proper functioning of centrosomes. Centrosomes are essential for organising microtubules and coordinating cell division within the cell.
What happens if there are variants in the PCNT gene?
Variants in the PCNT gene can lead to an altered or non-functional pericentrin protein. This can disrupt cell division and microtubule assembly, contributing to developmental conditions such as microcephalic osteodysplastic primordial dwarfism type II.
How is microcephalic osteodysplastic primordial dwarfism type II (MOPDII) related to the PCNT gene?
MOPDII is primarily caused by pathogenic variants in the PCNT gene. These variants result in a defective pericentrin protein that cannot adequately support centrosome function, leading to the characteristic features of severe short stature, microcephaly, and skeletal issues.
References
- Willems M, Geneviève D, Borck G. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. Journal of medical genetics. 2010. PMID: 19643772
- Delaval B, Doxsey SJ. Pericentrin in cellular function and disease. The Journal of cell biology. 2010. PMID: 19951897
- Rauch A, Thiel CT, Schindler D. Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science (New York, N.Y.). 2008. PMID: 18174396