Seroatlas · Human Serome Atlas

CLCF1

Cardiotrophin-like cytokine factor 1

Also known as: BSF-3, BSF3, CISS2, CLC, CLCF1_HUMAN, NNT-1, NNT1, NR6

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q9UBD9
Gene
CLCF1
Ensembl
ENSG00000175505
Chromosome
11
Canonical length
225 aa
Protein class
Disease related genes, Human disease related genes, Metabolic proteins, Predicted secreted proteins
Subcellular location
Nuclear bodies,Vesicles
Secretome location
Secreted to blood

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

225 residues, UniProt reviewed canonical sequence.

>Q9UBD9|CLCF1
     1  MDLRAGDSWG MLACLCTVLW HLPAVPALNR TGDPGPGPSI QKTYDLTRYL EHQLRSLAGT
    61  YLNYLGPPFN EPDFNPPRLG AETLPRATVD LEVWRSLNDK LRLTQNYEAY SHLLCYLRGL
   121  NRQAATAELR RSLAHFCTSL QGLLGSIAGV MAALGYPLPQ PLPGTEPTWT PGPAHSDFLQ
   181  KMDDFWLLKE LQTWLWRSAK DFNRLKKKMQ PPAAAVTLHL GAHGF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLCF1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.37
Highest tissue expression
17 nTPM

Expression across tissuesHPA

Tissue

  • urinary bladder: 17 nTPM
  • gallbladder: 17 nTPM
  • endometrium: 17 nTPM
  • adipose tissue: 16 nTPM
  • fallopian tube: 16 nTPM
  • kidney: 16 nTPM

Single-cell type

  • endometrial glandular cells: 77 nCPM
  • fallopian secretory cells: 68 nCPM
  • endometrial luminal cells: 58 nCPM
  • epididymal efferent duct absorptive cells: 57 nCPM
  • epididymal efferent duct ciliated cells: 54 nCPM
  • schwann cells: 37 nCPM

Immune cell

  • eosinophil: 15 nTPM
  • naive B-cell: 14 nTPM
  • memory B-cell: 11 nTPM
  • gdT-cell: 11 nTPM
  • non-classical monocyte: 11 nTPM
  • memory CD8 T-cell: 8.3 nTPM

Brain region

  • thalamus: 9.6 nTPM
  • cerebral cortex: 9.2 nTPM
  • medulla oblongata: 8.9 nTPM
  • amygdala: 8.8 nTPM
  • basal ganglia: 8.5 nTPM
  • choroid plexus: 8.5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLCF1.

Disease | AllUniProt

Conditions CLCF1 is implicated in, by any mechanism.

  • Crisponi/Cold-induced sweating syndrome 2 (CISS2) MIM:610313

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 71 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Cold-induced sweating syndrome 2

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.32
gnomAD pLI
0.95
gnomAD missense Z
1.12
DepMap mean gene effect
-0.02
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CLCF1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CLCF1 as an antibody target. Whether an autoantibody or antibody against CLCF1 could matter depends on whether native CLCF1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CLCF1 is annotated as secreted, so native CLCF1 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label CLCF1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/CLCF1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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