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CLCF1
cardiotrophin like cytokine factor 1
The CLCF1 gene provides instructions for the cardiotrophin like cytokine factor 1 protein, which is critical for the proper development and maintenance of the nervous system, including motor neurons and sweat gland regulation. The CLCF1 gene, or cardiotrophin like cytokine factor 1, plays an important role in cellular signalling pathways, particularly those involved in nervous system development and maintenance.
CLCF1 is located on the long (q) arm of chromosome 11, at band 11q13.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The CLCF1 gene encodes the protein known as cardiotrophin like cytokine factor 1. This protein functions in partnership with cytokine receptor-like factor 1 (CRLF1) to create a complex integral to cell signalling. This complex then interacts with the ciliary neurotrophic factor receptor (CNTFR) on cell surfaces, initiating signals that affect cell development and function.
The CNTFR signalling pathway, primarily modulated by the CLCF1 protein complex, is crucial for the healthy development and ongoing function of the nervous system. It supports the survival of nerve cells, particularly those that control muscle movement, and influences sweat regulation in response to environmental factors like temperature.
What the gene does
The CLCF1 gene directs the production of cardiotrophin like cytokine factor 1 (CLCF1) protein. This protein forms a crucial partnership with cytokine receptor-like factor 1 (CRLF1), establishing the CRLF1/CLCF1 protein complex. This complex then binds to the ciliary neurotrophic factor receptor (CNTFR) found on the surface of various cell types.
Upon binding, the CRLF1/CLCF1 complex initiates intracellular signalling cascades that are vital for cell development and function. This pathway is particularly significant for the nervous system, promoting the survival of neurons, especially motor neurons. It also contributes to the regulation of sweating via the sympathetic nervous system and is involved in the maturation of nerve cells that control sweat gland activity. Beyond the nervous system, this signalling pathway may also contribute to the body's inflammatory response and bone tissue development, though these roles are less well understood.
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Chromosome location
The CLCF1 gene is situated on chromosome 11, specifically at band 11q13.2. This genomic location positions the gene within a region that is systematically categorised within the human genome.
Protein structure
The CLCF1 protein comprises 225 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variations within the CLCF1 gene can impact the structure and function of the encoded protein. These genetic changes can range from small alterations, such as single nucleotide substitutions, to larger rearrangements, potentially leading to the production of a non-functional or abnormally functioning CLCF1 protein. The inheritance pattern for conditions associated with CLCF1 variants can vary.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Mutations in the CLCF1 gene are linked to conditions that affect body temperature regulation and other systemic abnormalities. One notable condition is cold-induced sweating syndrome, specifically referred to as CISS2 when caused by CLCF1 gene variants. This rare disorder is characterised by issues with thermoregulation.
No disease links recorded for this gene in our reference set.
UK clinical status
Frequently asked questions
What is the CLCF1 gene responsible for?
The CLCF1 gene provides instructions for making the cardiotrophin like cytokine factor 1 protein. This protein is essential for nervous system development and maintenance, including the survival of motor neurons and the regulation of sweat glands.
What happens if there is a mutation in the CLCF1 gene?
Mutations in the CLCF1 gene can lead to the production of a non-functional CLCF1 protein. This can result in conditions like cold-induced sweating syndrome (CISS2), which is characterised by problems with body temperature regulation.
How does the CLCF1 protein work with other proteins?
The CLCF1 protein partners with another protein called cytokine receptor-like factor 1 (CRLF1) to form a complex. This complex then binds to the ciliary neurotrophic factor receptor (CNTFR) on cell surfaces, triggering internal cell signalling that influences cell development and function.
References
- Hahn AF, Waaler PE, Kvistad PH. Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood. Four new cases. Journal of the neurological sciences. 2010. PMID: 20400119
- Rousseau F, Gauchat JF, McLeod JG. Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient. Proceedings of the National Academy of Sciences of the United States of America. 2006. PMID: 16782820
- Hahn AF, Jones DL, Knappskog PM. Cold-induced sweating syndrome: a report of two cases and demonstration of genetic heterogeneity. Journal of the neurological sciences. 2006. PMID: 16952376
- Vlotides G, Zitzmann K, Stalla GK. Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3)/cardiotrophin-like cytokine (CLC)--a novel gp130 cytokine with pleiotropic functions. Cytokine & growth factor reviews. 2004. PMID: 15450249
- Shi Y, Wang W, Yourey PA. Computational EST database analysis identifies a novel member of the neuropoietic cytokine family. Biochemical and biophysical research communications. 1999. PMID: 10448081
- Senaldi G, Varnum BC, Sarmiento U. Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. Proceedings of the National Academy of Sciences of the United States of America. 1999. PMID: 10500198