Details for: CNTFR

Gene ID: 1271

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CNTFR

Ensembl ID: ENSG00000122756

Description: ciliary neurotrophic factor receptor

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • progenitor cell CL0011026
    CSI 13.49
    rCSI 28.69%
    PRS 68.82
  • peripheral nervous system neuron CL2000032
    CSI 8.04
    rCSI 10.96%
    PRS 64.4
  • forebrain radial glial cell CL0013000
    CSI 4.84
    rCSI 15.52%
    PRS 76.31
  • melanocyte CL0000148
    CSI 3.7
    rCSI 2.74%
    PRS 66.04
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.26
    rCSI 3.9%
    PRS 54.33
  • subcutaneous adipocyte CL0002521
    CSI 2.82
    rCSI 14.46%
    PRS 77.11
  • myofibroblast cell CL0000186
    CSI 2.71
    rCSI 3.75%
    PRS 71.82
  • interstitial cell of Cajal CL0002088
    CSI 2.48
    rCSI 3.15%
    PRS 78.76
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.3
    rCSI 4.07%
    PRS 53.58
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.27
    rCSI 3.66%
    PRS 56.22
  • interneuron CL0000099
    CSI 2.25
    rCSI 4.53%
    PRS 62.58
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.2
    rCSI 2.54%
    PRS 65.37
  • skin fibroblast CL0002620
    CSI 2.16
    rCSI 1.86%
    PRS 75.83
  • neural crest cell CL0011012
    CSI 2.14
    rCSI 1.69%
    PRS 60.67
  • adipocyte CL0000136
    CSI 2.13
    rCSI 2.73%
    PRS 63.83
  • alveolar adventitial fibroblast CL4028006
    CSI 2.07
    rCSI 3.27%
    PRS 75.12
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.01
    rCSI 2.59%
    PRS 55.78
  • Bergmann glial cell CL0000644
    CSI 1.94
    rCSI 2.65%
    PRS 65.17
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.92
    rCSI 2.47%
    PRS 69.56
  • radial glial cell CL0000681
    CSI 1.91
    rCSI 2.65%
    PRS 71.76
  • keratocyte CL0002363
    CSI 1.79
    rCSI 4.3%
    PRS 78.1
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.78
    rCSI 2.22%
    PRS 52.44
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.7
    rCSI 5.03%
    PRS 74.83
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.66
    rCSI 2.78%
    PRS 54.46
  • Schwann cell CL0002573
    CSI 1.58
    rCSI 4.5%
    PRS 69.64
  • glioblast CL0000030
    CSI 1.57
    rCSI 2.5%
    PRS 64.8
  • amacrine cell CL0000561
    CSI 1.39
    rCSI 4.03%
    PRS 62.23
  • smooth muscle cell CL0000192
    CSI 1.26
    rCSI 3%
    PRS 72.17
  • mesodermal cell CL0000222
    CSI 1.13
    rCSI 1.36%
    PRS 71.21
  • glial cell CL0000125
    CSI 1.13
    rCSI 4.29%
    PRS 63.51
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.06
    rCSI 2.37%
    PRS 55.05
  • mesenchymal cell CL0008019
    CSI 1.02
    rCSI 2.58%
    PRS 66.71
  • cardiac neuron CL0010022
    CSI 0.91
    rCSI 2.92%
    PRS 70.24
  • stromal cell CL0000499
    CSI 0.87
    rCSI 2.46%
    PRS 68.77
  • neural progenitor cell CL0011020
    CSI 0.85
    rCSI 3.72%
    PRS 61.93
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.75
    rCSI 2.16%
    PRS 73.48
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.74
    rCSI 2.32%
    PRS 56.23
  • neuroplacodal cell CL0000032
    CSI 0.58
    rCSI 5.38%
    PRS 77.76
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.48
    rCSI 1.74%
    PRS 52.54
  • enteric neuron CL0007011
    CSI 0.42
    rCSI 6.25%
    PRS 82.33
  • mesenchymal stem cell CL0000134
    CSI 0.16
    rCSI 1.74%
    PRS 81.34

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CNTFR](/details-gene/1271) (ciliary neurotrophic factor receptor) encodes the alpha subunit of the receptor for ciliary neurotrophic factor (CNTF), a potent survival factor for various neuronal populations. As a component of the IL-6-type cytokine receptor family, [CNTFR](/details-gene/1271) is essential for mediating CNTF signaling, which plays a crucial role in the development, survival, and differentiation of cells within the nervous system. **Overall**, expression data reveals that [CNTFR](/details-gene/1271) is a highly significant marker for diverse neural cell types, including [progenitor cell](/details-cell/CL0011026)s and [peripheral nervous system neuron](/details-cell/CL2000032)s, underscoring its foundational role in neurodevelopment and neuronal maintenance. ## Cellular Roles and Expression Landscape The expression profile of [CNTFR](/details-gene/1271) firmly establishes its identity as a key gene in the nervous system, particularly in developing and mature neuronal populations. **Overall**, it shows the highest significance in [progenitor cell](/details-cell/CL0011026)s (CSI: 13.49), [peripheral nervous system neuron](/details-cell/CL2000032)s (CSI: 8.04), and [forebrain radial glial cell](/details-cell/CL0013000)s (CSI: 4.84), which are critical precursor cells in cortical development. Its consistent high expression in various interneuron subtypes, such as [VIP GABAergic cortical interneuron](/details-cell/CL4023016)s and [sncg GABAergic cortical interneuron](/details-cell/CL4023015)s, further highlights its importance in the establishment and function of neural circuits. Beyond the nervous system, [CNTFR](/details-gene/1271) is also significantly expressed in several non-neuronal cell types. These include [melanocyte](/details-cell/CL0000148)s, [subcutaneous adipocyte](/details-cell/CL0002521)s, [myofibroblast cell](/details-cell/CL0000186)s, and [skin fibroblast](/details-cell/CL0002620)s. This broader expression pattern suggests that CNTF signaling may have pleiotropic effects, potentially influencing tissue development, metabolic regulation, or repair processes in mesenchymal and ectodermal lineages. ## Pathways and Molecular Function [CNTFR](/details-gene/1271) functions as the ligand-binding alpha subunit of a heterotrimeric receptor complex, which also includes the signal-transducing components LIFR and gp130 ([Link](https://pubmed.ncbi.nlm.nih.gov/1648265/)). Its primary molecular function is defined as `ciliary neurotrophic factor receptor activity` ([GO:0004897](https://www.ebi.ac.uk/QuickGO/term/GO:0004897)) and more broadly as `cytokine receptor activity` ([GO:0004896](https://www.ebi.ac.uk/QuickGO/term/GO:0004896)). The gene's involvement in biological processes is strongly tied to its role in neurodevelopment and cell survival. It is a key component of the `ciliary neurotrophic factor-mediated signaling pathway` ([GO:0070120](https://www.ebi.ac.uk/QuickGO/term/GO:0070120)) and plays a critical role in `nervous system development` ([GO:0007399](https://www.ebi.ac.uk/QuickGO/term/GO:0007399)) and the `negative regulation of motor neuron apoptotic process` ([GO:2000672](https://www.ebi.ac.uk/QuickGO/term/GO:2000672)). This anti-apoptotic function is consistent with its established role as a neurotrophic factor receptor. Pathway analysis places [CNTFR](/details-gene/1271) within the `Interleukin-6 family signaling` ([R-HSA-6783589](https://reactome.org/content/detail/R-HSA-6783589)) and `Cytokine signaling in immune system` ([R-HSA-1280215](https://reactome.org/content/detail/R-HSA-1280215)) cascades. While its expression is predominantly neural, its participation in these pathways highlights the conserved signaling architecture shared between the nervous and immune systems. Cellularly, the encoded protein is localized to the `external side of plasma membrane` ([GO:0009897](https://www.ebi.ac.uk/QuickGO/term/GO:0009897)) where it forms the `ciliary neurotrophic factor receptor complex` ([GO:0070110](https://www.ebi.ac.uk/QuickGO/term/GO:0070110)). ## Research Directions The well-defined role of [CNTFR](/details-gene/1271) in neuronal survival and development presents several avenues for future research, particularly concerning its function in specific cell populations and its therapeutic potential. **Proposed Hypotheses:** 1. Given its high significance in [progenitor cell](/details-cell/CL0011026)s and [forebrain radial glial cell](/details-cell/CL0013000)s, [CNTFR](/details-gene/1271) signaling may be essential for regulating the balance between self-renewal and neuronal differentiation in the developing cortex. Its activation could be a key signal that commits these precursors to a specific neuronal fate. 2. The notable expression of [CNTFR](/details-gene/1271) in [subcutaneous adipocyte](/details-cell/CL0002521)s suggests a potential, and less-studied, role in metabolic homeostasis. CNTF signaling in adipocytes may influence lipolysis, glucose uptake, or the secretion of adipokines, thereby linking neurotrophic pathways with systemic energy balance. **Experimental Approach:** To test the first hypothesis regarding its role in cortical development, a gain-of-function and loss-of-function approach in a human forebrain organoid model would be highly informative. CRISPR-Cas9-mediated knockout of [CNTFR](/details-gene/1271) in human induced pluripotent stem cells (iPSCs) could be performed prior to organoid differentiation. The resulting [CNTFR](/details-gene/1271)-deficient organoids would then be compared to isogenic controls. Key readouts would include single-cell RNA sequencing (scRNA-seq) to map developmental trajectories and quantify the proportions of radial glia, intermediate progenitors, and mature neurons, as well as immunofluorescence staining for markers of proliferation (Ki67), radial glia (SOX2, PAX6), and neurons (TBR1, CTIP2) to assess cytoarchitecture and cell fate decisions. **Therapeutic Potential:** [CNTFR](/details-gene/1271) represents a promising therapeutic target for neurodegenerative diseases characterized by motor neuron loss, such as amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy. The therapeutic strategy would involve **activation** of the receptor to promote neuronal survival and inhibit apoptosis. The ligand, CNTF, has been tested clinically with limited success due to poor bioavailability and side effects. Therefore, developing small molecule agonists that specifically target and activate the [CNTFR](/details-gene/1271) complex or gene therapies to enhance its expression in affected neurons could offer a more effective and targeted approach to treatment.

Genular Protein ID: 3441002583

Symbol: CNTFR_HUMAN

Name: Ciliary neurotrophic factor receptor subunit alpha

UniProtKB Accession Codes:

P26992 Q5U050

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 EMDB 5 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 21 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PIR 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 6 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1648265

Title: The receptor for ciliary neurotrophic factor.

PubMed ID: 1648265

DOI: 10.1126/science.1648265

PubMed ID: 7774913

Title: Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor.

PubMed ID: 7774913

DOI: 10.1016/0888-7543(95)80121-2

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 19386761

Title: Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130.

PubMed ID: 19386761

DOI: 10.1091/mbc.e09-02-0168

PubMed ID: 26858303

Title: Cytokine-like factor 1, an essential facilitator of cardiotrophin-like cytokine:ciliary neurotrophic factor receptor alpha signaling and sorLA-mediated turnover.

PubMed ID: 26858303

DOI: 10.1128/mcb.00917-15

PubMed ID: 12707266

Title: Solution structure of the C-terminal domain of the ciliary neurotrophic factor (CNTF) receptor and ligand free associations among components of the CNTF receptor complex.

PubMed ID: 12707266

DOI: 10.1074/jbc.m301976200

Sequence Information:

  • Length: 372
  • Mass: 40633
  • Checksum: B2F3F73DE8F8750E
  • Sequence:
    • MAAPVPWACC AVLAAAAAVV YAQRHSPQEA PHVQYERLGS DVTLPCGTAN WDAAVTWRVN 
GTDLAPDLLN GSQLVLHGLE LGHSGLYACF HRDSWHLRHQ VLLHVGLPPR EPVLSCRSNT 
YPKGFYCSWH LPTPTYIPNT FNVTVLHGSK IMVCEKDPAL KNRCHIRYMH LFSTIKYKVS 
ISVSNALGHN ATAITFDEFT IVKPDPPENV VARPVPSNPR RLEVTWQTPS TWPDPESFPL 
KFFLRYRPLI LDQWQHVELS DGTAHTITDA YAGKEYIIQV AAKDNEIGTW SDWSVAAHAT 
PWTEEPRHLT TEAQAAETTT STTSSLAPPP TTKICDPGEL GSGGGPSAPF LVSVPITLAL 
AAAAATASSL LI