CRLF1 explained

Cytokine receptor-like factor 1 is a protein that in humans is encoded by the CRLF1 gene.^{[1] [2]}

Function

This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells.^[2]

Clinical significance

Mutations in this gene are associated with two conditions, both rare:

• Cold-induced sweating syndrome, characterized by profuse hyperhidrosis in cold environmental temperature and characteristic craniofacial and skeletal features)^{[3] [4]}
• Crisponi syndrome (CS), characterized by neonatal-onset paroxysmal muscular contractions, abnormal function of the autonomic nervous system and craniofacial and skeletal manifestations such as thick and arched eyebrows, a short nose with anteverted nostrils, full cheeks, an inverted upper lip and a small mouth.^[3]

It is unknown whether the two conditions are distinct clinical entities or a single clinical entity with variable expressions.^[3] Other characteristic features in CRLF1 mutation include marfanoid habitus with progressive kyphoscoliosis and craniofacial characteristics including dolichocephaly, a slender face with poor expression, a nose with hypoplastic nares, malar hypoplasia and prognathism.^[3]

Further reading

• Elson GC, Lelièvre E, Guillet C . CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. . Nat. Neurosci. . 3 . 9 . 867–72 . 2000 . 10966616 . 10.1038/78765 . 25766998 . etal.
• Lelièvre E, Plun-Favreau H, Chevalier S . Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component. . J. Biol. Chem. . 276 . 25 . 22476–84 . 2001 . 11294841 . 10.1074/jbc.M101681200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Knappskog PM, Majewski J, Livneh A . Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene. . Am. J. Hum. Genet. . 72 . 2 . 375–83 . 2003 . 12509788 . 10.1086/346120 . 379230 . etal.
• Clark HF, Gurney AL, Abaya E . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 . etal.
• Heese K, Yamada T, Akatsu H . Characterizing the new transcription regulator protein p60TRP. . J. Cell. Biochem. . 91 . 5 . 1030–42 . 2005 . 15034937 . 10.1002/jcb.20010 . 28107229 . etal.
• Zhang Z, Henzel WJ . Signal peptide prediction based on analysis of experimentally verified cleavage sites. . Protein Sci. . 13 . 10 . 2819–24 . 2005 . 15340161 . 10.1110/ps.04682504 . 2286551 .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Dagoneau N, Bellais S, Blanchet P . Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes. . Am. J. Hum. Genet. . 80 . 5 . 966–70 . 2007 . 17436251 . 10.1086/513608 . 1852726 . etal.
• Crisponi L, Crisponi G, Meloni A . Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1. . Am. J. Hum. Genet. . 80 . 5 . 971–81 . 2007 . 17436252 . 10.1086/516843 . 1852730 . etal.

External links

• Hahn, Angelika F. Knappskog, Per Morten (March 3, 2011 [Updated August 12, 2021]). "Cold-Induced Sweating Syndrome Including Crisponi Syndrome". GeneReviews.
• "Search: '601559 193700 601680 272430 601378 604237 607672 610313 272430 601378 604237 607672 610313 (Search in: MIM number). Online Mendelian Inheritance in Man entries about cold-induced sweating syndrome including Crisponi syndrome.

Notes and References

1. 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 . 161 . 3 . 1371–9 . Aug 1998 . 10.4049/jimmunol.161.3.1371 . 9686600 .
2. Web site: Entrez Gene: CRLF1 cytokine receptor-like factor 1.
3. Yamazaki M, Kosho T, Kawachi S, Mikoshiba M, Takahashi J, Sano R, Oka K, Yoshida K, Watanabe T, Kato H, Komatsu M, Kawamura R, Wakui K, Knappskog PM, Boman H, Fukushima Y . Cold-induced sweating syndrome with neonatal features of Crisponi syndrome: longitudinal observation of a patient homozygous for a CRLF1 mutation . Am. J. Med. Genet. A . 152A . 3 . 764–9 . March 2010 . 20186812 . 10.1002/ajmg.a.33315 . 19694775 .
4. Rousseau F, Gauchat JF, McLeod JG, Chevalier S, Guillet C, Guilhot F, Cognet I, Froger J, Hahn AF, Knappskog PM, Gascan H, Boman H . Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient . Proc. Natl. Acad. Sci. U.S.A. . 103 . 26 . 10068–73 . June 2006 . 16782820 . 1502507 . 10.1073/pnas.0509598103 . 2006PNAS..10310068R . free .