C11orf73

C11orf73 is a gene located on chromosome 11 in humans, encoding a protein of unknown biological function. Despite its classification as a “protein of unknown function,” research has highlighted its potential relevance, especially in cancer studies. 

This article provides a concise overview of C11orf73, focusing on its potential as a cancer biomarker and its current clinical significance.

What is C11orf73?

C11orf73 refers both to a gene and the protein it encodes. The term "orf" stands for "open reading frame," meaning the gene has a segment of DNA that codes for a protein. 

Also known as HIKESHI, the C11orf73 gene is located on chromosome 11. It plays a critical role in cellular stress management, particularly in response to heat shock, by facilitating the nuclear import of heat shock proteins (HSP70). These proteins stabilize cellular proteins and prevent aggregation under stress conditions. 

Mutations or dysfunction in C11orf73 impair this process, leading to HIKESHI-related hypomyelinating leukodystrophy, a severe neurological disorder.

HIKESHI-Related Hypomyelinating Leukodystrophy

HIKESHI-related hypomyelinating leukodystrophy is characterized by progressive loss of myelin in the brain and spinal cord, resulting in motor dysfunction, cognitive decline, hypotonia, dystonia, spasticity, and nystagmus. 

Symptoms often begin in infancy, with delayed or regressed motor skills and cognitive impairment. HIKESHI-related leukodystrophy is most commonly observed in individuals of Ashkenazi Jewish descent, with the c.160G>C mutation being a frequent cause. The disorder follows an autosomal recessive inheritance pattern, and genetic testing is essential for diagnosis.

Neuropathologically, affected individuals show near-total absence of myelin and reactive astrocytes and microglia, which indicate neuroinflammation. Brain MRIs typically reveal hypomyelination and a thin corpus callosum. Genetic testing to detect C11orf73 mutations, particularly the c.160G>C variant, is essential, especially for high-risk populations.

Though there is no cure, early diagnosis aids in symptom management and supportive care. Patients are at increased risk of severe morbidity or death, particularly during febrile illnesses. Management primarily focuses on symptom relief, with multidisciplinary care often needed to address neurological impairments.

C11orf73 and Cancer

While C11orf73's involvement in cellular stress responses has been well-studied, its potential role in cancer research is still under investigation. 

Research has observed changes in C11orf73 expression levels, both increases and decreases, across various cancer types, such as breast and lung cancers. These findings suggest that C11orf73 may influence cancer development or progression, although its clinical relevance remains uncertain. 

Additionally, genetic variations, including single nucleotide polymorphisms (SNPs) in the C11orf73 gene, have been associated with cancer risk in some studies. However, more research is needed to validate these associations and determine whether C11orf73 can be reliably used as a biomarker for cancer in clinical practice.

When to Assess C11orf73 Expression or Genetic Variation

Genetic testing for HIKESHI-related hypomyelinating leukodystrophy should be considered in individuals, particularly those of Ashkenazi Jewish descent, presenting with early-onset motor dysfunction, developmental regression, and signs of myelin abnormalities on MRI. 

It is also recommended for individuals with a family history of neurodevelopmental disorders or those with unexplained symptoms during febrile illnesses.

C11orf73 is being studied in various cancer types, including but not limited to breast and lung cancers. However, findings are not consistent across all cancer types, and the results are still considered preliminary.

Test Procedure and Interpretation

The following section outlines the typical test procedure and interpretation for C11orf73 genetic testing:

Testing Procedure

C11orf73 testing involves genetic testing, typically requiring blood, saliva, or cheek swab samples, although specialized laboratories may recommend different sample types. 

A cheek swab or saliva sample is easily obtained from the comfort of home, while blood samples typically require a blood draw.

Normal Reference Ranges

Normal reference ranges for C11orf73 genetic testing are considered to be without mutations that can alter the activity of the C11orf73 proteins.

Clinical Implications of Positive C11orf73 Mutations

The clinical implications of a positive C11orf73 mutation test result will vary by individual, although C11orf73 mutations in symptomatic patients signal an immediate need for further assessment and possibly treatment. 

Patients or practitioners with questions about the clinical implications of C11orf73 mutations should seek further assessment with a genetic counselor or expert. 

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