CNTFR

Chr 9

ciliary neurotrophic factor receptor

NCBI Gene: 1271ENSG00000122756UniProt: P26992

This gene encodes a member of the type 1 cytokine receptor family. The encoded protein is the ligand-specific component of a tripartite receptor for ciliary neurotrophic factor, which plays a critical role in neuronal cell survival, differentiation and gene expression. Binding of ciliary neurotrophic factor to the encoded protein recruits the transmembrane components of the receptor, gp130 and leukemia inhibitory factor receptor, facilitating signal transduction. Single nucleotide polymorphisms in this gene may be associated with variations in muscle strength, as well as early onset of eating disorders. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

126
ClinVar variants
70
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CNTFR
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 53 VUS of 126 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.955
Z-score 3.56
OE 0.11 (0.04–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.60Z-score
OE missense 0.71 (0.62–0.80)
166 obs / 235.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.04–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.62–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 2 / 18.6Missense obs/exp: 166 / 235.0Syn Z: 0.44

ClinVar Variant Classifications

126 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic8
VUS53
Likely Benign2
62
Pathogenic
8
Likely Pathogenic
53
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
8
0
8
VUS
0
43
10
0
53
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total045800125

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CNTFR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts.
Buers I et al.·Clin Genet
2020Review
Potential Risk Factors and Therapeutic Targets for Dilated Cardiomyopathy Identified Through Mendelian Randomization Analysis.
Wang H et al.·J Am Heart Assoc
2026
Engineered interleukin-6-derived cytokines recruit artificial receptor complexes and disclose CNTF signaling via the OSMR.
Rafii P et al.·J Biol Chem
2024
The amino acid exchange R28E in ciliary neurotrophic factor (CNTF) abrogates interleukin-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR).
Wagener EM et al.·J Biol Chem
2014
RNA-Seq analysis reveals sex-dependent transcriptomic profiles of human subacromial bursa stratified by tear etiology.
Rai MF et al.·J Orthop Res
2022
Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL.
Li X et al.·Pediatr Blood Cancer
2013
Expanding the mutational spectrum of CRLF1 in Crisponi/CISS1 syndrome.
Piras R et al.·Hum Mutat
2014
Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women.
Khanal P et al.·Genes (Basel)
2022Functional
microRNA-146a Promotes Growth of Acute Leukemia Cells by Downregulating Ciliary Neurotrophic Factor Receptor and Activating JAK2/STAT3 Signaling.
Wang L et al.·Yonsei Med J
2019
Cancer Stemness-Based Prognostic Immune-Related Gene Signatures in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.
Li N et al.·Front Endocrinol (Lausanne)
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The Anti-Obesogenic Effects of Muscadine Grapes through Ciliary Neurotrophic Factor Receptor (Cntfr) and Histamine Receptor H1 (Hrh1) Genes in 3T3-L1 Differentiated Mouse Cells.
Messeha SS et al.·Nutrients
2024Functional
Transcription factor TP63 mediates LncRNA CNTFR-AS1 to promote DNA damage induced by neodymium oxide nanoparticles via homologous recombination repair.
Gao L et al.·Environ Pollut
2023
Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma.
Kim JW et al.·Nat Med
2019
CNTFR Genotype and Sprint/power Performance: Case-control Association and Functional Studies.
Miyamoto-Mikami E et al.·Int J Sports Med
2016Functional
clc is co-expressed with clf or cntfr in developing mouse muscles.
de Bovis B et al.·Cell Commun Signal
2005🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools