CLCF1 cardiotrophin like cytokine factor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLCF1provided by HGNC
Official Full Name: cardiotrophin like cytokine factor 1provided by HGNC
Primary source: HGNC:HGNC:17412
See related: Ensembl:ENSG00000175505 MIM:607672; AllianceGenome:HGNC:17412
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CLC; NR6; BSF3; NNT1; BSF-3; CISS2; NNT-1
Summary: 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]
Expression: Broad expression in gall bladder (RPKM 9.3), endometrium (RPKM 7.5) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (67364168..67374177, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (67358280..67368294, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (67131639..67141648, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Intrahepatic paracrine signaling by cardiotrophin-like cytokine factor 1 ameliorates diet-induced NASH in mice.
Title: Intrahepatic paracrine signaling by cardiotrophin-like cytokine factor 1 ameliorates diet-induced NASH in mice.
CLCF1 Is a Novel Potential Immune-Related Target With Predictive Value for Prognosis and Immunotherapy Response in Glioma.
Title: CLCF1 Is a Novel Potential Immune-Related Target With Predictive Value for Prognosis and Immunotherapy Response in Glioma.
CRLF1 and CLCF1 in Development, Health and Disease.
Title: CRLF1 and CLCF1 in Development, Health and Disease.
Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-kappaB signaling pathway.
Title: Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway.
Association of cardiotrophin-like cytokine factor 1 levels in peripheral blood mononuclear cells with bone mineral density and osteoporosis in postmenopausal women.
Title: Association of cardiotrophin-like cytokine factor 1 levels in peripheral blood mononuclear cells with bone mineral density and osteoporosis in postmenopausal women.
Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts.
Title: Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts.
we nominate blockade of CLCF1-CNTFR signaling as a novel therapeutic opportunity for lung adenocarcinoma and potentially for other tumor types in which CLCF1 is present in the tumor microenvironment.
Title: Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma.
Very low-density lipoproteins (VLDL)- and LDL-CLCF1 binding was confirmed using proximity and ligand blots assays. CLCF1-induced STAT3 phosphorylation was significantly reduced when the cytokine was complexed with VLDL.
Title: Effect of human very low-density lipoproteins on cardiotrophin-like cytokine factor 1 (CLCF1) activity.
CLF-1, based on its binding site for CLC and on two additional and independent sites for CNTFRalpha and sorLA, is a key player in CLC and CNTFRalpha signaling and turnover.
Title: Cytokine-Like Factor 1, an Essential Facilitator of Cardiotrophin-Like Cytokine:Ciliary Neurotrophic Factor Receptor α Signaling and sorLA-Mediated Turnover.
Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders.
Title: Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cold-induced sweating syndrome 2 MedGen: C1853198 OMIM: 610313 GeneReviews: Cold-Induced Sweating Syndrome including Crisponi Syndrome	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH68115 (e-PCR)
- UniSTS:37379

CLC_34 (e-PCR)
- UniSTS:277100

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to ciliary neurotrophic factor receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables ciliary neurotrophic factor receptor binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables cytokine activity	NAS Non-traceable Author Statement more info	PubMed
enables growth factor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell surface receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell surface receptor signaling pathway via JAK-STAT	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor signaling pathway via JAK-STAT	ISS Inferred from Sequence or Structural Similarity more info
involved_in cytokine-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of B cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of B cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of astrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of immunoglobulin production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of isotype switching to IgE isotypes	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tyrosine phosphorylation of STAT protein	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tyrosine phosphorylation of STAT protein	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of CNTFR-CLCF1 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CNTFR-CLCF1 complex	IDA Inferred from Direct Assay more info	PubMed
part_of CRLF-CLCF1 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CRLF-CLCF1 complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in extracellular region	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: cardiotrophin-like cytokine factor 1

Names: B-cell stimulatory factor 3; B-cell-stimulating factor 3; CRLF1 associated cytokine-like factor 1; neurotrophin-1/B-cell stimulating factor-3; novel neurotrophin-1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013377.1 RefSeqGene

Range

5580..15010

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166212.2 → NP_001159684.1 cardiotrophin-like cytokine factor 1 isoform 2 precursor

See identical proteins and their annotated locations for NP_001159684.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (2) has a shorter N-terminus when compared to isoform 1.

Source sequence(s)

AK298052, BC012939, DC393345

Consensus CDS

CCDS53666.1

UniProtKB/Swiss-Prot

Q9UBD9

Related

ENSP00000434122.1, ENST00000533438.1

Conserved Domains (1) summary

cl21565
Location:46 → 202

LIF_OSM; LIF / OSM family
NM_013246.3 → NP_037378.1 cardiotrophin-like cytokine factor 1 isoform 1 precursor

See identical proteins and their annotated locations for NP_037378.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Though this isoform has a predicted signal peptide at amino acids 1-27, experiments show it is retained within the cell.

Source sequence(s)

BC012939, BM846622

Consensus CDS

CCDS31617.1

UniProtKB/Swiss-Prot

B4DNT4, Q6NZA4, Q9UBD9

Related

ENSP00000309338.7, ENST00000312438.8

Conserved Domains (1) summary

cl21565
Location:56 → 212

LIF_OSM; LIF / OSM family