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CENPJ
centrosome assembly and centriole elongation protein
CENPJ is located on the long (q) arm of chromosome 13, at band 13q12.12-q12.13. Arm ratio per GRCh38 - banding schematic.
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Overview
CENPJ encodes centrosome assembly and centriole elongation protein, a structural component of the centrosome that coordinates cell division. The centrosome serves as the primary organising centre for microtubules, the cellular scaffolding that ensures chromosomes segregate correctly when cells divide. During embryonic development, proper centrosome function is particularly important in the rapidly dividing cells of the developing brain and skeleton.
Pathogenic variants in CENPJ follow an autosomal recessive inheritance pattern, meaning two altered copies are required to cause disease. When both copies carry pathogenic changes, affected individuals typically present with Seckel syndrome, a condition characterised by severe microcephaly, intrauterine growth restriction, and distinctive facial features. The gene is located on chromosome 13 and produces a protein of 1,338 amino acids that localises to the centrosome throughout the cell cycle.
What the gene does
The CENPJ protein functions primarily at the centrosome, where it facilitates centriole duplication during the cell cycle. Centrioles are cylindrical structures that form the core of centrosomes, and each dividing cell must precisely duplicate its centriole pair to ensure the daughter cells receive correct chromosome numbers. CENPJ coordinates the early stages of procentriole assembly, working alongside other centrosomal proteins to establish the structural foundation for new centrioles.
The protein contains an alpha/beta-tubulin binding region (amino acids 319-394) that enables direct interaction with tubulin, the building block of microtubules and centriolar structures. Additionally, CENPJ features an extensive interaction region with STIL protein (amino acids 895-1,338), a partnership essential for recruiting and stabilising centriolar components. Together, these molecular interactions ensure centrosomes duplicate once and only once per cell cycle, maintaining genomic stability across cell divisions.
During brain development, neural progenitor cells undergo numerous rounds of division, making them particularly sensitive to centrosomal defects. Disrupted CENPJ function impairs these divisions, reducing the final number of neurons and resulting in the characteristically small brain size seen in affected individuals.
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Chromosome location
CENPJ is located on the long arm of chromosome 13 at position 13q12.12-q12.13. This chromosomal region contains numerous genes involved in developmental processes. The gene spans a substantial genomic interval and produces transcripts that encode the 1,338-amino-acid centrosomal protein.
Protein structure
The CENPJ protein comprises 1,338 amino acids organised into distinct functional regions. A notable structural feature is the alpha/beta-tubulin binding region spanning amino acids 319-394, which mediates the protein's association with tubulin subunits during centriole assembly. The C-terminal half contains an extensive interaction region with STIL (amino acids 895-1,338), critical for coordinating procentriole formation.
A substantial proportion of the protein consists of disordered regions distributed throughout the sequence: amino acids 190-211, 386-414, 436-479, 521-551, 611-789, 845-865, and 1,096-1,153. These intrinsically disordered segments likely provide structural flexibility, enabling CENPJ to adopt different conformations when interacting with various centrosomal partners during the cell cycle. Such disorder is common in proteins that serve as scaffolds, allowing them to accommodate multiple binding partners sequentially or simultaneously.
Key variants
Pathogenic variants in CENPJ typically result in loss of protein function, disrupting centrosome duplication and impairing normal development. Most disease-causing changes are nonsense or frameshift variants that introduce premature stop codons, leading to truncated, non-functional proteins. Missense variants affecting critical functional regions, particularly the tubulin-binding or STIL-interaction domains, can also abolish protein activity. Because CENPJ-related conditions follow autosomal recessive inheritance, affected individuals carry pathogenic variants on both gene copies.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in CENPJ cause Seckel syndrome, a rare autosomal recessive condition characterised by severe microcephaly (significantly reduced head circumference), intrauterine growth restriction, proportionate short stature, and distinctive facial features. The severity of microcephaly reflects impaired neural progenitor division during foetal brain development, when centrosomal function is critical for generating sufficient neurons. Affected individuals typically present at birth with markedly reduced head size and low birth weight, with ongoing growth restriction through childhood and into adulthood.
- Seckel syndrome Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic CENPJ 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
CENPJ appears on multiple NHS Genomic Medicine Service gene panels, reflecting its established role in developmental disorders. The gene holds green (high-evidence) classification on the Developmental Disorders Genotype to Phenotype (DDG2P) panel and the Fetal Anomalies panel (R21), indicating strong evidence for pathogenicity. It is also included with green ratings on the Intellectual Disability panel (R29), the Intrauterine Growth Restriction and IGF Abnormalities panel, and the Severe Microcephaly panel (R88). These panel memberships guide UK clinical laboratories in interpreting CENPJ variants detected through prenatal or postnatal genetic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is Seckel syndrome and how does CENPJ cause it?
Seckel syndrome is an autosomal recessive condition characterised by severe microcephaly, intrauterine growth restriction, and short stature. Pathogenic variants in CENPJ disrupt centrosome function, impairing the cell divisions required for normal brain and skeletal development during foetal growth.
How is CENPJ inherited?
CENPJ follows autosomal recessive inheritance, meaning an individual must inherit a pathogenic variant from both parents to develop a related condition. Carriers with one altered copy typically show no symptoms but can pass the variant to their children.
Why does CENPJ dysfunction particularly affect brain size?
The developing brain relies on rapid, repeated cell divisions of neural progenitor cells to generate sufficient neurons. Because CENPJ is essential for accurate cell division, its loss disproportionately affects the brain, where even small reductions in progenitor divisions lead to markedly fewer neurons and severe microcephaly.