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9 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CNGA4
cyclic nucleotide gated channel subunit alpha 4
Chromosome 11 · 11p15.4
NCBI Gene: 1262Ensembl: ENSG00000132259.14HGNC: HGNC:2152UniProt: Q8IV77
9PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranemonoatomic cation transmembrane transportcGMP bindingnon-motile cilium membraneneurodegenerative diseasepeptic ulcer diseasemathematical abilityduodenal ulcer
✦AI Summary

CNGA4 encodes a pore-forming subunit of the olfactory cyclic nucleotide-gated (CNG) channel, a heteromeric complex also containing CNGA2 and CNGB1b in a 2:1:1 stoichiometry 1. In olfactory sensory neuron cilia, CNGA4 mediates cAMP-dependent Ca²⁺ and cation influx, converting chemical odorant stimulation into electrical signals 2. The channel conducts both cAMP- and cGMP-gated currents with permeability for monovalent and divalent cations. CNGA4 contains an IQ-type calmodulin-binding site critical for rapid odorant adaptation; Ca²⁺-bound calmodulin binds this site to inhibit channel activity, providing negative feedback that enables sensory neurons to quickly desensitize and readapt to sustained odorant exposure 34. CNGA4 also contributes a functional module that stabilizes the channel's open state at physiological cAMP concentrations 5. Additionally, the CNGA2 N-terminus, required for PIP3-mediated channel regulation, is functionally silent in heteromeric channels, suggesting CNGA4's structural context modulates regulatory mechanisms 6. Disease relevance is limited; CNGA4 hypermethylation has been observed in carcinogen-exposed cells and lung cancer tissues, though its direct pathogenic role remains unclear 7.

Sources cited
1
CNGA4 is a component of native olfactory CNG channel heterotetramer with 2:1:1 CNGA2/CNGA4/CNGB1b stoichiometry; structure shows calmodulin-mediated gating
PMID: 41131016
2
CNGA4 is a modulatory CNG channel subunit; its disruption causes profound defects in adaptation of peptide-evoked potentials in the main olfactory epithelium
PMID: 16481428
3
CNGA4 contains an IQ-type calmodulin-binding site necessary and sufficient for Ca²⁺/calmodulin-mediated feedback inhibition of native olfactory CNG channels
PMID: 15195096
4
CNGA4 is required for calmodulin-mediated negative feedback inhibition and rapid adaptation of olfactory CNG channels to odorants
PMID: 11739960
5
CNGA4 contributes a functional module that stabilizes the open state of the olfactory cAMP-gated channel at low cAMP concentrations
PMID: 19822638
6
CNGA4 is part of heteromeric olfactory CNG channels regulated by PIP3 and calmodulin through the CNGA2 N-terminus
PMID: 17032767
7
CNGA4 is differentially hypermethylated and suppressed in benzo(a)pyrene-transformed bronchial epithelial cells
PMID: 28359976
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.24Weak
peptic ulcer diseaseOpen Targets
0.08Suggestive
mathematical abilityOpen Targets
0.08Suggestive
duodenal ulcerOpen Targets
0.05Suggestive
Leber congenital amaurosis 10Open Targets
0.05Suggestive
facial morphologyOpen Targets
0.04Suggestive
Abnormality of the earOpen Targets
0.04Suggestive
Absent thumb - short stature - immunodeficiencyOpen Targets
0.03Suggestive
hypogonadotropic hypogonadismOpen Targets
0.03Suggestive
Kallmann syndromeOpen Targets
0.03Suggestive
obstructive sleep apneaOpen Targets
0.03Suggestive
Peptic ulcerOpen Targets
0.03Suggestive
gastroesophageal reflux diseaseOpen Targets
0.02Suggestive
LeishmaniasisOpen Targets
0.01Suggestive
COVID-19Open Targets
0.00Suggestive
Developmental cataractOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
viral diseaseOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
Hereditary breast cancerOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CNGA3Protein interaction100%CNGB3Protein interaction100%CALM3Protein interaction100%ADCY3Protein interaction97%CALML3Protein interaction97%CALML4Protein interaction96%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
46%
Ovary
24%
Lung
18%
Liver
10%
Heart
0%
Gene Interaction Network
Click a node to explore
CNGA4CNGA3CNGB3CALM3ADCY3CALML3CALML4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IV77
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.92LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.70 [0.53–0.92]
RankingsWhere CNGA4 stands among ~20K protein-coding genes
  • #17,302of 20,598
    Most Researched9
  • #8,514of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedCNGA4
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
Structural mechanisms of assembly, gating, and calmodulin modulation of human olfactory CNG channel.
PMID: 41131016
Nat Commun · 2025
1.00
2
Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands.
PMID: 16481428
J Neurosci · 2006
0.89
3
PMID: 28359976
Environ Pollut · 2017
0.78
4
Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits.
PMID: 11739960
Science · 2001
0.67
5
Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels.
PMID: 17032767
Proc Natl Acad Sci U S A · 2006
0.56