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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CNTF
ciliary neurotrophic factor
Chromosome 11 · 11q12.1
NCBI Gene: 1270Ensembl: ENSG00000242689.3HGNC: HGNC:2169UniProt: P26441
114PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
interleukin-6 receptor bindingciliary neurotrophic factor-mediated signaling pathwaynegative regulation of oligodendrocyte progenitor proliferationcell surface receptor signaling pathway via STATopen-angle glaucomaglaucomatype 2 diabetes mellitusinjury
✦AI Summary

CNTF is a pleiotropic cytokine and member of the IL-6 cytokine family 1 that functions primarily as a survival factor for diverse neuronal cell types, including sensory, sympathetic, and motor neurons 2. The protein is not secreted via the classical endoplasmic reticulum-Golgi pathway but accumulates in the cytoplasm of myelinating Schwann cells and astrocytes 2. Mechanistically, CNTF signals through a receptor complex containing gp130 and activates JAK2/STAT3 and ERK1/2 pathways 34. In the retina, CNTF demonstrates robust neuroprotective effects, promoting both rod and cone photoreceptor survival and regeneration in degenerative models 5. CNTF also supports retinal ganglion cell survival and axon regeneration 5. Beyond photoreceptor protection, CNTF enhances retinal pigment epithelium survival, modulates polarized cytokine secretion, and increases fluid absorption through CFTR channel activation 3. Clinical relevance extends to retinal degenerative diseases, with ongoing trials investigating CNTF implants for achromatopsia patients with CNGB3 mutations 6. Emerging evidence suggests CNTF also regulates vascular function through JAK2/STAT3-dependent mechanisms in angiotensin II-induced hypertension 4. Despite these neuroprotective roles, CNTF is dispensable for embryonic development, with knockout mice showing postnatal motor neuron loss specifically 2.

Sources cited
1
CNTF promotes rod and cone photoreceptor survival and cone outer segment regeneration; supports retinal ganglion cell survival and axon regeneration
PMID: 22182585
2
Clinical trials are underway studying CNTF implants as treatment for achromatopsia patients with CNGB3 mutations
PMID: 26196097
3
CNTF is not secreted classically but accumulates in cytoplasm of Schwann cells and astrocytes; supports multiple neuronal cell types; CNTF knockout mice show postnatal motor neuron loss
PMID: 7852996
4
CNTF is a member of the IL-6 family of cytokines that share gp130 as a common receptor
PMID: 38232478
5
CNTF increases RPE survival and fluid absorption through JAK/STAT3 signaling via CFTR channel activation; modulates polarized cytokine secretion
PMID: 21912637
6
CNTF regulates blood pressure and vascular function through JAK2/STAT3-dependent mechanisms in angiotensin II-induced hypertension
PMID: 39851048
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.26Weak
glaucomaOpen Targets
0.23Weak
type 2 diabetes mellitusOpen Targets
0.21Weak
injuryOpen Targets
0.16Weak
hypertensionOpen Targets
0.10Suggestive
amyotrophic lateral sclerosisOpen Targets
0.09Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.09Suggestive
obesityOpen Targets
0.08Suggestive
heart failureOpen Targets
0.08Suggestive
diabetes mellitusOpen Targets
0.07Suggestive
familial amyotrophic lateral sclerosisOpen Targets
0.07Suggestive
hypertrophic cardiomyopathyOpen Targets
0.07Suggestive
HyperglycemiaOpen Targets
0.06Suggestive
hereditary neuropathy with liability to pressure palsiesOpen Targets
0.06Suggestive
amyotrophic lateral sclerosis type 22Open Targets
0.06Suggestive
frontotemporal dementia and/or amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
amyotrophic lateral sclerosis-parkinsonism-dementia complexOpen Targets
0.05Suggestive
type 1 diabetes mellitusOpen Targets
0.05Suggestive
sporadic amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OSMRProtein interaction100%LIFRProtein interaction100%EPOProtein interaction100%THPOProtein interaction97%LIFProtein interaction97%IL6Protein interaction96%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
24%
Liver
12%
Lung
10%
Heart
10%
Ovary
4%
Gene Interaction Network
Click a node to explore
CNTFOSMRLIFREPOTHPOLIFIL6
PROTEIN STRUCTURE
Preparing viewer…
PDB1CNT · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.55LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.02 [0.68–1.55]
RankingsWhere CNTF stands among ~20K protein-coding genes
  • #4,143of 20,598
    Most Researched114 · top quartile
  • #15,460of 17,882
    Most Constrained (LOEUF)1.55
Genes detectedCNTF
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CNTF and retina.
PMID: 22182585
Prog Retin Eye Res · 2012
1.00
2
Achromatopsia: a review.
PMID: 26196097
Curr Opin Ophthalmol · 2015
0.90
3
Ciliary neurotrophic factor.
PMID: 7852996
J Neurobiol · 1994
0.80
4
Interleukin-6 Family of Cytokines in Cancers.
PMID: 38232478
J Interferon Cytokine Res · 2024
0.70
5
Lipid Nanoparticle-Mediated Delivery of mRNA Into the Mouse and Human Retina and Other Ocular Tissues.
PMID: 38980261
Transl Vis Sci Technol · 2024
0.60