CRLF1 Gene

HGNC Family	Fibronectin type III domain containing
Name	cytokine receptor-like factor 1
Description	This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cytokine receptor–like factor 1 (CRLF1) is a multifunctional soluble protein that modulates cytokine signaling in diverse tissues. In neuronal cells, for example, upregulation of CRLF1 enhances resistance to oxidative stress by a cell‐autonomous mechanism independent of its traditional role as a co‐ligand for the ciliary neurotrophic factor receptor complex, thereby promoting motor neuron survival and neuroprotection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, mutations in the CRLF1 gene cause disorders such as Crisponi syndrome and cold‐induced sweating syndrome, with evidence suggesting that the kinetics of CRLF1 secretion largely determine disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the kidney, when CRLF1 forms a heterodimer with cardiotrophin‐like cytokine factor 1 (CLCF1), this complex can attenuate increases in glomerular albumin permeability by regulating STAT3 phosphorylation, thereby protecting the glomerular filtration barrier."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In joint tissues, elevated expression of CRLF1 in damaged cartilage has been implicated in osteoarthritis. The CRLF1/CLCF1 complex appears to disrupt cartilage homeostasis by promoting chondrocyte proliferation while suppressing the production of key extracellular matrix components, a mechanism that may contribute to disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, particularly papillary thyroid carcinoma, overexpression of CRLF1 is associated with more aggressive tumor behavior. CRLF1 enhances cell proliferation, migration, invasion, and epithelial–mesenchymal transition by activating the ERK1/2 and AKT pathways, and its interaction with MYH9 further supports these oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CRLF1 has been shown to bind directly to the endocytic receptor sorLA, a connection that appears to facilitate formation, turnover, and downstream signaling of the tripartite complex that includes CLCF1 and the ciliary neurotrophic factor receptor α."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, CRLF1 functions as a critical modulator of cytokine signaling, with roles spanning neural protection, regulation of glomerular permeability, cartilage degeneration, and tumor progression. Its diverse activities and involvement in multiple signaling networks underscore its potential as a therapeutic target in a range of pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brendan D Looyenga, James Resau, Jeffrey P MacKeigan "}, {"type": "b", "children": [{"type": "t", "text": "Cytokine receptor-like factor 1 (CRLF1) protects against 6-hydroxydopamine toxicity independent of the gp130/JAK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0066548"}], "href": "https://doi.org/10.1371/journal.pone.0066548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23818941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23818941"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jana Herholz, Alessandra Meloni, Mara Marongiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2010.253"}], "href": "https://doi.org/10.1038/ejhg.2010.253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21326283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21326283"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Natalie A Sims "}, {"type": "b", "children": [{"type": "t", "text": "Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytokine Growth Factor Rev (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cytogfr.2015.07.014"}], "href": "https://doi.org/10.1016/j.cytogfr.2015.07.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26198769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26198769"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mukut Sharma, Jianping Zhou, Jean-François Gauchat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Janus kinase 2/signal transducer and activator of transcription 3 inhibitors attenuate the effect of cardiotrophin-like cytokine factor 1 and human focal segmental glomerulosclerosis serum on glomerular filtration barrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.trsl.2015.03.002"}], "href": "https://doi.org/10.1016/j.trsl.2015.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25843671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25843671"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "John F Bateman, Lynn Rowley, Daniele Belluoccio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptomics of wild-type mice and mice lacking ADAMTS-5 activity identifies genes involved in osteoarthritis initiation and cartilage destruction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.37900"}], "href": "https://doi.org/10.1002/art.37900"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23436205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23436205"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shi-Tong Yu, Qian Zhong, Ren-Hui Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0352-0"}], "href": "https://doi.org/10.1038/s41419-018-0352-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29515111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29515111"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shi-Tong Yu, Bai-Hui Sun, Jun-Na Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRLF1-MYH9 Interaction Regulates Proliferation and Metastasis of Papillary Thyroid Carcinoma Through the ERK/ETV4 Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Endocrinol (Lausanne) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fendo.2020.00535"}], "href": "https://doi.org/10.3389/fendo.2020.00535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32982961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32982961"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jakob Vejby Larsen, Anders Mejer Kristensen, Lone Tjener Pallesen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytokine-Like Factor 1, an Essential Facilitator of Cardiotrophin-Like Cytokine:Ciliary Neurotrophic Factor Receptor α Signaling and sorLA-Mediated Turnover."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00917-15"}], "href": "https://doi.org/10.1128/MCB.00917-15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26858303"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26858303"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura Crisponi, Insa Buers, Frank Rutsch "}, {"type": "b", "children": [{"type": "t", "text": "CRLF1 and CLCF1 in Development, Health and Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23020992"}], "href": "https://doi.org/10.3390/ijms23020992"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35055176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35055176"}]}]}]}
Synonyms	CISS1, NR6, CLF-1, CISS, ZCYTOR5
Proteins	CRLF1_HUMAN
NCBI Gene ID	9244
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CRLF1 has 6,514 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for CRLF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CRLF1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRLF1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRLF1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CRLF1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CRLF1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CRLF1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CRLF1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CRLF1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRLF1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CRLF1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CRLF1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRLF1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CRLF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CRLF1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRLF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CRLF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CRLF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CRLF1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CRLF1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CRLF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CRLF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CRLF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CRLF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CRLF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CRLF1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CRLF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CRLF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CRLF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CRLF1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CRLF1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CRLF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CRLF1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CRLF1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CRLF1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CRLF1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CRLF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CRLF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CRLF1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CRLF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CRLF1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CRLF1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.