CLCF1
Cardiotrophin-like Cytokine Factor 1
Gene Information Card
| Symbol | CLCF1 |
|---|---|
| Full Name | Cardiotrophin-like cytokine factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 23529 ncbi.nlm.nih.gov/gene/23529 |
| Ensembl ID | ENSG00000175592 |
| UniProt ID | Q9UBD9 |
| OMIM ID | 607672 |
| HGNC ID | 13522 |
| Aliases | BBS3, CLC, CLCF1, NR6, NNT-1, BSF-3 |
Description
CLCF1 encodes cardiotrophin-like cytokine factor 1, a member of the IL-6 family of cytokines. It forms a heterodimer with cytokine receptor-like factor 1 (CRLF1) to activate the JAK/STAT signaling pathway. CLCF1 is involved in neurotrophism, B-cell stimulation, and regulation of immune responses. Mutations in CLCF1 are associated with cold-induced sweating syndrome and Crisponi syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cold-induced sweating syndrome | Loss-of-function mutations in CLCF1 impair neurotrophic signaling, leading to defective sympathetic innervation of sweat glands. | OMIM #272430 |
| Crisponi syndrome | Homozygous or compound heterozygous mutations in CLCF1 disrupt CRLF1/CLCF1 complex formation, causing dysautonomia and muscle contractions. | OMIM #607672 |
| Congenital insensitivity to pain with anhidrosis (CIPA)-like phenotype | CLCF1 mutations may mimic NTRK1 defects, though evidence is limited. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.2 | Medium |
| Brain | 6.5 | Medium |
| Lung | 4.1 | Low |
| Liver | 2.3 | Low |
| Skeletal muscle | 3.7 | Low |
| Placenta | 12.1 | High |
| Testis | 9.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression in recombinant systems |
| HeLa | 7.2 | Moderate expression |
| K562 | 4.5 | Low expression |
| HepG2 | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.676C>T (p.Arg226*) | Nonsense | Rare | Loss of function; truncation of CLCF1 protein |
| c.731G>A (p.Arg244His) | Missense | Rare | Impaired heterodimerization with CRLF1 |
| c.832C>T (p.Arg278Cys) | Missense | Rare | Reduced secretion and signaling activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that disrupt protein folding, secretion, or receptor binding lead to loss of function, causing cold-induced sweating syndrome and Crisponi syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLCF1.
Dominant Negative (DN)
Dominant-negative effects are not established; most pathogenic mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IL-6 family signaling pathway (Reactome: R-HSA-447115)
• JAK-STAT signaling pathway (KEGG: hsa04630)
• Neurotrophin signaling pathway (KEGG: hsa04722)
Protein Summary
CLCF1 is a secreted cytokine of 225 amino acids (UniProt Q9UBD9) that forms a complex with CRLF1 and soluble IL-6 receptor beta (gp130) to activate STAT3. It is essential for the development of sympathetic neurons and regulation of B-cell responses. The protein contains a typical four-helix bundle cytokine fold. Mutations cause autosomal recessive disorders affecting thermoregulation and nociception.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCF1 Knockout HEK293 Cell Line | EDJ-KQ8046 | Human | 23529 | Details Get a Quote |
| CLCF1 Knockout A-549 Cell Line | EDJ-KQ32510 | Human | 23529 | Details Get a Quote |
| CLCF1 Knockout HCT 116 Cell Line | EDJ-KQ33854 | Human | 23529 | Details Get a Quote |
| CLCF1 Knockout HeLa Cell Line | EDJ-KQ33855 | Human | 23529 | Details Get a Quote |
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