CRLF1: Cytokine Receptor Like Factor 1
Key regulator of neuropoietic cytokine signaling and cold-induced sweating syndrome
Gene Information Card
| Symbol | CRLF1 |
|---|---|
| Full Name | Cytokine Receptor Like Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 9244 ncbi.nlm.nih.gov/gene/9244 |
| Ensembl ID | ENSG00000105711 |
| UniProt ID | O75462 |
| OMIM ID | 604237 |
| HGNC ID | 2364 |
| Aliases | CLF-1, CLF1, NR6, zcytor5 |
Description
CRLF1 encodes a cytokine receptor-like factor that forms a heterodimeric complex with cardiotrophin-like cytokine factor 1 (CLCF1). This complex acts as a ligand for the ciliary neurotrophic factor receptor (CNTFR) and is essential for neuropoietic cytokine signaling, including survival of motor neurons and regulation of immune responses. Mutations in CRLF1 cause cold-induced sweating syndrome (CISS) and Crisponi syndrome, characterized by impaired thermoregulation and autonomic dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cold-induced sweating syndrome 1 (CISS1) | Loss-of-function mutations in CRLF1 disrupt CNTFR signaling, leading to defective sympathetic neuron development and aberrant sweating upon cold exposure. | OMIM #272430; ClinVar |
| Crisponi syndrome (CISS2) | Similar loss-of-function mechanism; mutations impair neuropoietic cytokine signaling, causing hyperthermia, facial anomalies, and autonomic dysregulation. | OMIM #272430; ClinVar |
| Cold-induced sweating syndrome 2 (CISS2) | Mutations in CLCF1 (ligand partner) produce a phenotypically similar disorder, highlighting the shared pathway. | OMIM #610313; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 8.7 | Low |
| Lung | 6.2 | Low |
| Liver | 4.1 | Not detected |
| Kidney | 9.5 | Low |
| Testis | 15.8 | Medium |
| Skeletal muscle | 3.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.2 | Cervical adenocarcinoma |
| K562 | 7.8 | Leukemia |
| HepG2 | 5.1 | Hepatocellular carcinoma |
| A549 | 6.4 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.713G>A (p.Arg238His) | Missense | Rare | Loss of function; disrupts CNTFR binding |
| c.226C>T (p.Arg76*) | Nonsense | Rare | Premature stop; loss of function |
| c.832_833del (p.Leu278Glufs*12) | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most CRLF1 mutations are loss-of-function, impairing heterodimer formation with CLCF1 and subsequent CNTFR activation, leading to CISS/Crisponi syndrome.
Gain of Function (GOF)
No gain-of-function mutations reported in CRLF1.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Neuropoietic cytokine signaling pathway (CNTFR)
• JAK-STAT signaling pathway
• PI3K-Akt signaling pathway
Protein Summary
CRLF1 (CLF-1) is a secreted glycoprotein that forms a soluble heterodimeric complex with CLCF1. This complex binds to CNTFR and activates downstream JAK/STAT and MAPK pathways, critical for neuronal survival, thermoregulation, and immune modulation. The protein contains a cytokine-binding domain and a fibronectin type III domain. Defects in CRLF1 lead to cold-induced sweating syndrome and Crisponi syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRLF1 Knockout HEK293 Cell Line | EDJ-KQ5861 | Human | 9244 | Details Get a Quote |
| CRLF1 Knockout A-549 Cell Line | EDJ-KQ30682 | Human | 9244 | Details Get a Quote |
| CRLF1 Knockout HCT 116 Cell Line | EDJ-KQ30683 | Human | 9244 | Details Get a Quote |
| CRLF1 Knockout HeLa Cell Line | EDJ-KQ30684 | Human | 9244 | Details Get a Quote |
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