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Aliases for CLCF1 Gene

Aliases for CLCF1 Gene

  • Cardiotrophin Like Cytokine Factor 1 2 3 5
  • Novel Neurotrophin-1 2 3 4
  • CRLF1 Associated Cytokine-Like Factor 1 2 3
  • B-Cell-Stimulating Factor 3 3 4
  • BSF-3 3 4
  • NNT-1 3 4
  • BSF3 3 4
  • NNT1 3 4
  • CLC 3 4
  • Neurotrophin-1/B-Cell Stimulating Factor-3 3
  • Cardiotrophin-Like Cytokine Factor 1 3
  • Cold-Induced Sweating Syndrome 2 2
  • B-Cell Stimulatory Factor 3 3
  • B-Cell Stimulating Factor 3 2
  • CISS2 3
  • NR6 3

External Ids for CLCF1 Gene

Previous GeneCards Identifiers for CLCF1 Gene

  • GC11M066890
  • GC11M067131
  • GC11M063460

Summaries for CLCF1 Gene

Entrez Gene Summary for CLCF1 Gene

  • 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.[provided by RefSeq, Oct 2009]

GeneCards Summary for CLCF1 Gene

CLCF1 (Cardiotrophin Like Cytokine Factor 1) is a Protein Coding gene. Diseases associated with CLCF1 include Crisponi/Cold-Induced Sweating Syndrome 2 and Cold-Induced Sweating Syndrome. Among its related pathways are Interleukin-6 family signaling and Regulation of lipid metabolism Insulin signaling-generic cascades. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and cytokine activity.

UniProtKB/Swiss-Prot for CLCF1 Gene

  • Cytokine with B-cell stimulating capability. Binds to and activates the ILST/gp130 receptor.

Gene Wiki entry for CLCF1 Gene

Additional gene information for CLCF1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLCF1 Gene

Genomics for CLCF1 Gene

GeneHancer (GH) Regulatory Elements for CLCF1 Gene

Promoters and enhancers for CLCF1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J066965 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 17.3 +405.1 405125 6.8 HDGF FOXA2 MLX ARID4B SIN3A DMAP1 YY1 SLC30A9 FOS DEK RAD9A EIF1AD CLCF1 ENSG00000258297 KDM2A PC RBM4 RBM14 RPS6KB2 RCE1
GH11J068210 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 11.1 -838.9 -838930 4.7 HDGF ARNT ARID4B SIN3A DMAP1 IRF4 YY1 POLR2B ZNF766 ZNF213 KMT5B PPP6R3 TPCN2 RAD9A ENSG00000255031 IGHMBP2 ENSG00000260808 C11orf24 CLCF1 CORO1B
GH11J066957 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 11.1 +416.2 416237 2.9 HDGF PKNOX1 CLOCK MLX ARID4B NEUROD1 SIN3A DMAP1 YY1 SLC30A9 PC KDM2A RBM14 RBM4 EIF1AD RAB1B ENSG00000255320 SART1 ENSG00000258297 LOC105369352
GH11J066636 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 11.1 +735.8 735841 3.8 HDGF PKNOX1 SMAD1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 RBM4 ACTN3 EIF1AD RBM14 KDM2A SART1 ENSG00000255320 ENSG00000258297 CORO1B RELA
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CLCF1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CLCF1 gene promoter:
  • STAT3
  • Sp1
  • GATA-2
  • Nkx2-5

Genomic Locations for CLCF1 Gene

Genomic Locations for CLCF1 Gene
10,010 bases
Minus strand
10,010 bases
Minus strand

Genomic View for CLCF1 Gene

Genes around CLCF1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLCF1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLCF1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLCF1 Gene

Proteins for CLCF1 Gene

  • Protein details for CLCF1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Cardiotrophin-like cytokine factor 1
    Protein Accession:
    Secondary Accessions:
    • B4DNT4
    • Q6NZA4

    Protein attributes for CLCF1 Gene

    225 amino acids
    Molecular mass:
    25176 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for CLCF1 Gene


neXtProt entry for CLCF1 Gene

Post-translational modifications for CLCF1 Gene

  • Glycosylation at Asn29
  • Modification sites at PhosphoSitePlus

Other Protein References for CLCF1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Protein Products

  • Abcam proteins for CLCF1

No data available for DME Specific Peptides for CLCF1 Gene

Domains & Families for CLCF1 Gene

Gene Families for CLCF1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for CLCF1 Gene

Suggested Antigen Peptide Sequences for CLCF1 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the IL-6 superfamily.
  • Belongs to the IL-6 superfamily.
genes like me logo Genes that share domains with CLCF1: view

Function for CLCF1 Gene

Molecular function for CLCF1 Gene

UniProtKB/Swiss-Prot Function:
Cytokine with B-cell stimulating capability. Binds to and activates the ILST/gp130 receptor.

Phenotypes From GWAS Catalog for CLCF1 Gene

Gene Ontology (GO) - Molecular Function for CLCF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IPI 15272019
GO:0005125 cytokine activity IDA,NAS 10500198
GO:0005127 contributes_to ciliary neurotrophic factor receptor binding IDA 10966616
GO:0005515 protein binding IPI 10966616
GO:0008083 growth factor activity TAS 14632778
genes like me logo Genes that share ontologies with CLCF1: view
genes like me logo Genes that share phenotypes with CLCF1: view

Human Phenotype Ontology for CLCF1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CLCF1 Gene

MGI Knock Outs for CLCF1:
  • Clcf1 Clcf1<tm1Zou>
  • Clcf1 Clcf1<tm1.1(KOMP)Vlcg>

Animal Model Products

  • Taconic Biosciences Mouse Models for CLCF1

CRISPR Products

miRNA for CLCF1 Gene

miRTarBase miRNAs that target CLCF1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLCF1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CLCF1 Gene

Localization for CLCF1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLCF1 Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CLCF1 gene
Compartment Confidence
extracellular 5
mitochondrion 2
nucleus 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CLCF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IDA,TAS --
GO:0005615 extracellular space IEA --
GO:0005622 intracellular IEA --
GO:0070062 extracellular exosome HDA --
GO:0097058 CRLF-CLCF1 complex IDA 10966616
genes like me logo Genes that share ontologies with CLCF1: view

Pathways & Interactions for CLCF1 Gene

genes like me logo Genes that share pathways with CLCF1: view

Pathways by source for CLCF1 Gene

SIGNOR curated interactions for CLCF1 Gene


Gene Ontology (GO) - Biological Process for CLCF1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002639 positive regulation of immunoglobulin production ISS --
GO:0007166 cell surface receptor signaling pathway ISS --
GO:0007259 JAK-STAT cascade ISS --
GO:0008284 positive regulation of cell proliferation IDA 10966616
GO:0010469 regulation of signaling receptor activity IEA --
genes like me logo Genes that share ontologies with CLCF1: view

Drugs & Compounds for CLCF1 Gene

(1) Drugs for CLCF1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for CLCF1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CLCF1: view

Transcripts for CLCF1 Gene

mRNA/cDNA for CLCF1 Gene

(2) REFSEQ mRNAs :
(8) Additional mRNA sequences :
(411) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CLCF1 Gene

Cardiotrophin-like cytokine factor 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLCF1

Alternative Splicing Database (ASD) splice patterns (SP) for CLCF1 Gene

No ASD Table

Relevant External Links for CLCF1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CLCF1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CLCF1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CLCF1 Gene

This gene is overexpressed in Monocytes (19.4), Urine (15.9), and Tlymphocyte (13.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CLCF1 Gene

NURSA nuclear receptor signaling pathways regulating expression of CLCF1 Gene:


SOURCE GeneReport for Unigene cluster for CLCF1 Gene:


mRNA Expression by UniProt/SwissProt for CLCF1 Gene:

Tissue specificity: Expressed predominantly in lymph nodes, spleen, peripheral blood lymphocytes, bone marrow, and fetal liver.

Evidence on tissue expression from TISSUES for CLCF1 Gene

  • Kidney(4.3)
  • Lung(4.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CLCF1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Head and neck:
  • brain
  • cheek
  • chin
  • cranial nerve
  • ear
  • face
  • forehead
  • head
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • pharynx
  • skull
  • tooth
  • vocal cord
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • pelvis
  • ankle
  • arm
  • digit
  • elbow
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shoulder
  • toe
  • ulna
  • upper limb
  • wrist
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • sweat gland
  • vertebrae
genes like me logo Genes that share expression patterns with CLCF1: view

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for CLCF1 Gene

Orthologs for CLCF1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CLCF1 Gene

Organism Taxonomy Gene Similarity Type Details
(Canis familiaris)
Mammalia CLCF1 34 33
  • 92.74 (n)
(Mus musculus)
Mammalia Clcf1 16 34 33
  • 91.7 (n)
(Rattus norvegicus)
Mammalia Clcf1 33
  • 89.54 (n)
(Bos Taurus)
Mammalia CLCF1 34 33
  • 87.19 (n)
(Ornithorhynchus anatinus)
Mammalia CLCF1 34
  • 79 (a)
(Monodelphis domestica)
Mammalia CLCF1 34
  • 31 (a)
(Pan troglodytes)
Mammalia CTF2 34
  • 29 (a)
(Gallus gallus)
Aves CLCF1 34 33
  • 74.16 (n)
(Anolis carolinensis)
Reptilia CLCF1 34
  • 63 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia clcf1 33
  • 60.9 (n)
Str.16134 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.32246 33
(Danio rerio)
Actinopterygii LOC562247 33
  • 54.74 (n)
clcf1 34
  • 24 (a)
Species where no ortholog for CLCF1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CLCF1 Gene

Gene Tree for CLCF1 (if available)
Gene Tree for CLCF1 (if available)
Evolutionary constrained regions (ECRs) for CLCF1: view image

Paralogs for CLCF1 Gene

No data available for Paralogs for CLCF1 Gene

Variants for CLCF1 Gene

Sequence variations from dbSNP and Humsavar for CLCF1 Gene

SNP ID Clin Chr 11 pos Variation AA Info Type
rs104894198 pathogenic, Cold-induced sweating syndrome 2 67,365,493(-) G/A/T coding_sequence_variant, stop_gained, synonymous_variant
rs104894203 pathogenic, Cold-induced sweating syndrome 2, Cold-induced sweating syndrome 2 (CISS2) [MIM:610313] 67,365,224(-) C/A/T coding_sequence_variant, missense_variant
rs137853934 pathogenic, Cold-induced sweating syndrome 2 67,367,597(-) A/G coding_sequence_variant, missense_variant
rs137853935 pathogenic, Cold-induced sweating syndrome 2 67,365,138(-) A/G stop_lost, terminator_codon_variant
rs1000576087 -- 67,372,004(-) G/A intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CLCF1 Gene

Variant ID Type Subtype PubMed ID
dgv52n111 CNV deletion 26073780
esv3361899 CNV duplication 20981092
nsv1070466 CNV deletion 25765185
nsv468603 CNV loss 19166990
nsv555253 CNV loss 21841781
nsv7220 OTHER inversion 18451855

Variation tolerance for CLCF1 Gene

Residual Variation Intolerance Score: 57.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.61; 45.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLCF1 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLCF1 Gene

Disorders for CLCF1 Gene

MalaCards: The human disease database

(3) MalaCards diseases for CLCF1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search CLCF1 in MalaCards View complete list of genes associated with diseases


  • Cold-induced sweating syndrome 2 (CISS2) [MIM:610313]: 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. {ECO:0000269 PubMed:16782820}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CLCF1

genes like me logo Genes that share disorders with CLCF1: view

No data available for Genatlas for CLCF1 Gene

Publications for CLCF1 Gene

  1. Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient. (PMID: 16782820) Rousseau F … Boman H (Proceedings of the National Academy of Sciences of the United States of America 2006) 2 3 4 22 58
  2. Computational EST database analysis identifies a novel member of the neuropoietic cytokine family. (PMID: 10448081) Shi Y … Alderson RF (Biochemical and biophysical research communications 1999) 2 3 4 22 58
  3. Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. (PMID: 10500198) Senaldi G … Chang MS (Proceedings of the National Academy of Sciences of the United States of America 1999) 2 3 4 58
  4. Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin share a conserved binding site on the ciliary neurotrophic factor receptor alpha chain. (PMID: 18728012) Rousseau F … Gascan H (The Journal of biological chemistry 2008) 3 22 58
  5. Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes. (PMID: 17436251) Dagoneau N … Cormier-Daire V (American journal of human genetics 2007) 3 22 58

Products for CLCF1 Gene

Sources for CLCF1 Gene

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