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Genetics Home Reference: your guide to understanding genetic conditions
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CRLF1

Reviewed August 2012

What is the official name of the CRLF1 gene?

The official name of this gene is “cytokine receptor-like factor 1.”

CRLF1 is the gene's official symbol. The CRLF1 gene is also known by other names, listed below.

What is the normal function of the CRLF1 gene?

The CRLF1 gene provides instructions for making a protein called cytokine receptor-like factor 1 (CRLF1). This protein partners with a similar protein called cardiotrophin-like cytokine factor 1 (CLCF1), which is produced from the CLCF1 gene. Together, these two proteins form a unit known as the CRLF1/CLCF1 protein complex. This complex attaches (binds) to a receptor protein known as the ciliary neurotrophic factor receptor (CNTFR) on the surface of many types of cells. When the CRLF1/CLCF1 protein complex is bound to CNTFR, it triggers signaling inside the cell that affects cell development and function.

The CNTFR signaling pathway is primarily involved in the development and maintenance of the nervous system. It promotes the survival of nerve cells (neurons), particularly nerve cells that control muscle movement (motor neurons). The CNTFR pathway also plays a role in a part of the nervous system called the sympathetic nervous system, specifically in the regulation of sweating in response to temperature changes and other factors. This signaling pathway appears to be critical for the normal development and maturation of nerve cells that control the activity of sweat glands.

Studies suggest that the CNTFR signaling pathway also has functions outside the nervous system. It may be involved in the body's inflammatory response, which helps fight infection and facilitate tissue repair following an injury. This pathway may also be important for the development and maintenance of bone tissue. However, little is known about the role of CNTFR signaling in these processes.

Does the CRLF1 gene share characteristics with other genes?

The CRLF1 gene belongs to a family of genes called fibronectin type III domain containing (fibronectin type III domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the CRLF1 gene related to health conditions?

cold-induced sweating syndrome - caused by mutations in the CRLF1 gene

At least 10 mutations in the CRLF1 gene have been reported to cause cold-induced sweating syndrome, a rare condition characterized by problems with regulating body temperature and other abnormalities affecting many parts of the body. When this condition is caused by CRLF1 gene mutations, it is known as CISS1.

Mutations in the CRLF1 gene lead to the production of a nonfunctional version of the CRLF1 protein or greatly reduce the production of functional CRLF1 protein. Consequently, CRLF1 is unavailable to interact with the CLCF1 protein and bind to CNTFR, which disables the CNTFR signaling pathway.

Researchers believe that a failure of CNTFR signaling underlies the major features of cold-induced sweating syndrome. A loss of this signaling pathway during sympathetic nervous system development may help explain the abnormal sweating that is characteristic of this condition, including unusual sweating patterns and related problems with body temperature regulation. The CNTFR pathway's involvement in motor neuron development and bone development provides clues to some of the other signs and symptoms of the disorder, including distinctive facial features, facial muscle weakness, and skeletal abnormalities. However, little is known about how a lack of CNTFR signaling leads to these varied features.

Where is the CRLF1 gene located?

Cytogenetic Location: 19p12

Molecular Location on chromosome 19: base pairs 18,593,224 to 18,606,849

The CRLF1 gene is located on the short (p) arm of chromosome 19 at position 12.

The CRLF1 gene is located on the short (p) arm of chromosome 19 at position 12.

More precisely, the CRLF1 gene is located from base pair 18,593,224 to base pair 18,606,849 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about CRLF1?

You and your healthcare professional may find the following resources about CRLF1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the CRLF1 gene or gene products?

  • CISS
  • CISS1
  • class I cytokine receptor
  • CLF
  • CLF-1
  • CRLF1_HUMAN
  • cytokine-like factor 1
  • cytokine type 1 receptor CRLP-1
  • zcytor5

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding CRLF1?

cell ; class ; cytokine ; gene ; infection ; injury ; leukemia ; motor ; motor neuron ; nervous system ; neuron ; protein ; receptor ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Crisponi L, Crisponi G, Meloni A, Toliat MR, Nurnberg G, Usala G, Uda M, Masala M, Hohne W, Becker C, Marongiu M, Chiappe F, Kleta R, Rauch A, Wollnik B, Strasser F, Reese T, Jakobs C, Kurlemann G, Cao A, Nurnberg P, Rutsch F. Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1. Am J Hum Genet. 2007 May;80(5):971-81. Epub 2007 Mar 30. (http://www.ncbi.nlm.nih.gov/pubmed/17436252?dopt=Abstract)
  • Dagoneau N, Bellais S, Blanchet P, Sarda P, Al-Gazali LI, Di Rocco M, Huber C, Djouadi F, Le Goff C, Munnich A, Cormier-Daire V. Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes. Am J Hum Genet. 2007 May;80(5):966-70. Epub 2007 Mar 13. (http://www.ncbi.nlm.nih.gov/pubmed/17436251?dopt=Abstract)
  • Elson GC, Graber P, Losberger C, Herren S, Gretener D, Menoud LN, Wells TN, Kosco-Vilbois MH, Gauchat JF. Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family. J Immunol. 1998 Aug 1;161(3):1371-9. (http://www.ncbi.nlm.nih.gov/pubmed/9686600?dopt=Abstract)
  • Hahn AF, Jones DL, Knappskog PM, Boman H, McLeod JG. Cold-induced sweating syndrome: a report of two cases and demonstration of genetic heterogeneity. J Neurol Sci. 2006 Dec 1;250(1-2):62-70. Epub 2006 Sep 6. (http://www.ncbi.nlm.nih.gov/pubmed/16952376?dopt=Abstract)
  • Hahn AF, Waaler PE, Kvistad PH, Bamforth JS, Miles JH, McLeod JG, Knappskog PM, Boman H. Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood. Four new cases. J Neurol Sci. 2010 Jun 15;293(1-2):68-75. doi: 10.1016/j.jns.2010.02.028. Epub 2010 Apr 18. (http://www.ncbi.nlm.nih.gov/pubmed/20400119?dopt=Abstract)
  • Herholz J, Meloni A, Marongiu M, Chiappe F, Deiana M, Herrero CR, Zampino G, Hamamy H, Zalloum Y, Waaler PE, Crisponi G, Crisponi L, Rutsch F. Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders. Eur J Hum Genet. 2011 May;19(5):525-33. doi: 10.1038/ejhg.2010.253. Epub 2011 Feb 16. (http://www.ncbi.nlm.nih.gov/pubmed/21326283?dopt=Abstract)
  • Kass DJ. Cytokine-like factor 1 (CLF1): life after development? Cytokine. 2011 Sep;55(3):325-9. doi: 10.1016/j.cyto.2011.05.021. Epub 2011 Jun 28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21715184?dopt=Abstract)
  • Knappskog PM, Majewski J, Livneh A, Nilsen PT, Bringsli JS, Ott J, Boman H. Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene. Am J Hum Genet. 2003 Feb;72(2):375-83. Epub 2002 Dec 31. (http://www.ncbi.nlm.nih.gov/pubmed/12509788?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9244)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2012
Published: August 18, 2014