CLCF1

This gene is a member of the glycoprotein (gp)130 cytokine family and encodes cardiotrophin-like cytokine factor 1 (CLCF1). CLCF1 forms a heterodimer complex with cytokine receptor-like factor 1 (CRLF1). This dimer competes with ciliary neurotrophic factor (CNTF) for binding to the ciliary neurotrophic factor receptor (CNTFR) complex, and activates the Jak-STAT signaling cascade. CLCF1 can be actively secreted from cells by forming a complex with soluble type I CRLF1 or soluble CNTFR. CLCF1 is a potent neurotrophic factor, B-cell stimulatory agent and neuroendocrine modulator of pituitary corticotroph function. Defects in CLCF1 cause cold-induced sweating syndrome 2 (CISS2). This syndrome is characterized by a profuse sweating after exposure to cold as well as congenital physical abnormalities of the head and spine. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Full Name

Cardiotrophin Like Cytokine Factor 1

Function

In complex with CRLF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development (Probable). Also stimulates B-cells. Binds to and activates the ILST/gp130 receptor.

Biological Process

B cell differentiation Source: BHF-UCL
Cell surface receptor signaling pathway Source: BHF-UCL
Cytokine-mediated signaling pathway Source: Reactome
Negative regulation of neuron apoptotic process Source: BHF-UCL
Positive regulation of astrocyte differentiation Source: BHF-UCL
Positive regulation of B cell proliferation Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of immunoglobulin production Source: BHF-UCL
Positive regulation of isotype switching to IgE isotypes Source: BHF-UCL
Positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
Receptor signaling pathway via JAK-STAT Source: BHF-UCL

Cellular Location

Secreted

Involvement in disease

Crisponi/Cold-induced sweating syndrome 2 (CISS2):
An autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Patients manifest, in the neonatal period, orofacial weakness with impaired sucking and swallowing, resulting in poor feeding. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. These features are referred to as Crisponi syndrome and can result in early death in infancy. Patients who survive into childhood have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Additional abnormalities include a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis.