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

Summary

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Official Symbol: CLCF1provided by HGNC
Official Full Name: cardiotrophin-like cytokine factor 1provided by HGNC
Primary source: HGNC:17412
See related: Ensembl:ENSG00000175505; HPRD:09643; MIM:607672; Vega:OTTHUMG00000167669
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]

Genomic context

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Location :: 11q13.3

Sequence :: Chromosome: 11; NC_000011.9 (67131639..67141648, complement)

See CLCF1 in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin share a conserved binding site on the ciliary neurotrophic factor receptor alpha chain
Title: Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin share a conserved binding site on the ciliary neurotrophic factor receptor alpha chain.
activation of the Jak-STAT cascade is essential for corticotroph NNT-1/BSF-3 signaling.
Title: Novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) stimulates corticotroph function via a signal transducer and activator of transcription-dependent mechanism negatively regulated by suppressor of cytokine signaling-3.
Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRalpha.
Title: Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient.

Submit: New GeneRIF Correction

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Cold-induced sweating syndrome 2

MIM: 610313

Genetic Testing Registry

Summary from GeneReviews: Cold-Induced Sweating Syndrome including Crisponi Syndrome

Crisponi syndrome, the infantile presentation of cold-induced sweating syndrome (CISS), is characterized by dysmorphic features (distinctive facies; lower facial weakness; flexion deformity at the elbows; camptodactyly with fisted hands; misshapen feet and overriding toes); poor suck reflex and severely impaired swallowing; and often temperature spikes with increased risk of seizures and sudden death. During the first decade of life, children with CISS develop profuse sweating of their face, arms, and chest with ambient temperatures below 18 masculine to 22 masculine C and often with other stimuli including apprehension or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. In the second decade, progressive thoracolumbar kyphoscoliosis requires intervention.

Diagnosis Testing

The diagnosis of CISS/Crisponi syndrome is based on clinical findings and family history. Mutations in CRLF1 account for about 90% and mutations in CLCF1 account for about 10% of CISS and Crisponi syndrome. Molecular genetic testing of these two genes is available on a research basis only.

Genetic Counseling

Cold-induced sweating syndrome (CISS) and Crisponi syndrome are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. No laboratories listed in the GeneTests Laboratory Directory offer molecular genetic testing for prenatal diagnosis of CISS/Crisponi syndrome; however, prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutations have been identified.

References

PMID: 21370513

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q9UBD9	Q9UBD9	CLCF1	HPRD	PubMed
Q9UBD9	P26992	CNTFR	HPRD	PubMed
Q9UBD9	O75462	CRLF1	HPRD	PubMed
BioGRID:117075	BioGRID:107671	CNTFR	BioGRID	PubMed	Affinity Capture-Western; Co-purification
BioGRID:117075	BioGRID:114670	CRLF1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:117075	BioGRID:116446	PARK7	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Jak-STAT signaling pathway, conserved biosystem (from KEGG)
Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...

General gene information

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Markers

RH68115 (e-PCR)
- UniSTS:37379

CLC_34 (e-PCR)
- UniSTS:277100

Genotypes

See CLCF1 SNP Geneview Report
See CLCF1 SNP Genotype Report
See CLCF1 SNP Variation Viewer Report

Potential readthrough

Included gene: POLD4

Homology

Homologs of the CLCF1 gene: The CLCF1 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
JAK-STAT cascade	ISS Inferred from Sequence or Structural Similarity more info
cell surface receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
cytokine-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed
negative regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
negative regulation of neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of B cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of astrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of immunoglobulin production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of isotype switching to IgE isotypes	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of tyrosine phosphorylation of Stat3 protein	IDA Inferred from Direct Assay more info	PubMed
positive regulation of tyrosine phosphorylation of Stat3 protein	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
CNTFR-CLCF1 complex	IDA Inferred from Direct Assay more info	PubMed
CRLF-CLCF1 complex	IDA Inferred from Direct Assay more info	PubMed
extracellular region	IDA Inferred from Direct Assay more info	PubMed
extracellular region	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: cardiotrophin-like cytokine factor 1

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

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

5001..15010

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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

Conserved Domains (1) summary

cl17072
Location:46 – 202
Blast Score: 148

PRF; Plethodontid receptivity factor PRF
NM_013246.2 → NP_037378.1 cardiotrophin-like cytokine factor 1 isoform 1 precursor

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

Q9UBD9

Related

ENSP00000309338, OTTHUMP00000236394, ENST00000312438, OTTHUMT00000395478

Conserved Domains (1) summary

cl17072
Location:56 – 212
Blast Score: 150

PRF; Plethodontid receptivity factor PRF

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p10 Primary Assembly

Range

67131639..67141648, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

63460623..63470003, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018922.1 Alternate CHM1_1.0

Range

67051114..67061126, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01024038.1	None
genomic	ABBA01024039.1	None
genomic	AF176912.1	AAF00992.1
genomic	AMYH01003744.1 (16515..24977)	None
genomic	AMYH01003745.1	None
genomic	AP003419.3 (44632..54199)	None
genomic	CH471076.1	EAW74601.1
		EAW74602.1
genomic	GM662943.1	CAV33841.1
mRNA	AF172854.1	AAD54284.1
mRNA	AF176911.1	AAF00991.1
mRNA	AK298052.1	BAG60346.1
mRNA	AY049779.1	AAL15436.1
mRNA	BC012939.1	AAH12939.1
mRNA	BC066229.1	AAH66229.1
mRNA	BC066230.1	AAH66230.1
mRNA	BC066231.1	AAH66231.1
mRNA	BM846622.1	None
mRNA	DC393345.1	None
other-genetic	DQ891525.2	ABM82451.1
other-genetic	DQ894715.2	ABM85641.1