CNGA2: Cyclic Nucleotide Gated Channel Subunit Alpha 2
Key regulator of olfactory signal transduction and potential implications in cancer and sensory disorders
Gene Information Card
| Symbol | CNGA2 |
|---|---|
| Full Name | Cyclic Nucleotide Gated Channel Subunit Alpha 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq26.3 |
| NCBI Gene ID | 1260 ncbi.nlm.nih.gov/gene/1260 |
| Ensembl ID | ENSG00000183862 |
| UniProt ID | Q16280 |
| OMIM ID | 300338 |
| HGNC ID | 2149 |
| Aliases | CNG2, CNCA, CNG-2, OCNC1, OCNCalpha |
Description
CNGA2 encodes the alpha-2 subunit of cyclic nucleotide-gated (CNG) channels, which are nonselective cation channels activated by cyclic nucleotides such as cAMP and cGMP. This subunit is essential for olfactory signal transduction, where it mediates the depolarizing current in response to odorant-induced cAMP production. CNGA2 is primarily expressed in olfactory sensory neurons but also found in other tissues including brain, testis, and certain cancer cell lines. Mutations in CNGA2 are associated with olfactory dysfunction and have been implicated in tumorigenesis through altered calcium signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Olfactory dysfunction (anosmia/hyposmia) | Loss-of-function mutations impair CNG channel activity, preventing odorant-induced depolarization in olfactory neurons. | ClinVar, OMIM |
| Colorectal cancer | Altered CNGA2 expression may disrupt calcium homeostasis and promote proliferation. | COSMIC, NCBI Gene |
| Breast cancer | CNGA2 overexpression linked to poor prognosis; potential role in cAMP-mediated signaling. | COSMIC, literature |
| Prostate cancer | Somatic mutations and copy number alterations observed; functional impact under investigation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Olfactory mucosa | 12.5 | High |
| Brain (cerebellum) | 3.2 | Medium |
| Testis | 2.8 | Medium |
| Lung | 0.9 | Low |
| Colon | 0.5 | Low |
| Breast | 0.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.1 | Low endogenous expression |
| SH-SY5Y (neuroblastoma) | 1.5 | Moderate expression |
| HCT116 (colorectal) | 2.0 | Moderate expression |
| MCF7 (breast) | 3.5 | High expression |
| PC3 (prostate) | 1.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1645C>T (p.Arg549*) | Nonsense | <0.01% | Loss of function; truncated protein lacking C-terminal domain |
| c.1012G>A (p.Gly338Arg) | Missense | <0.01% | Impaired channel gating; reduced cAMP sensitivity |
| c.1780_1781del (p.Leu594fs) | Frameshift | <0.01% | Loss of function; premature stop codon |
| c.1234A>G (p.Ile412Val) | Missense | 0.02% | Likely benign; no functional change reported |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg549*, p.Leu594fs) lead to truncated or unstable protein, abolishing channel activity. Missense variants (e.g., p.Gly338Arg) impair cAMP-induced gating.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CNGA2 to date.
Dominant Negative (DN)
Heterozygous missense mutations may exert dominant-negative effects by co-assembling with wild-type subunits, reducing overall channel conductance.
View complete mutation data：
Gene Ontology (GO)
| • ion channel activity (GO:0005216) | • voltage-gated potassium channel complex (GO:0008076) |
| • integral component of membrane (GO:0016021) | • cAMP binding (GO:0030552) |
| • cGMP binding (GO:0030553) | • sensory perception of smell (GO:0007608) |
| • ion transport (GO:0006811) | • calcium ion transmembrane transport (GO:0070588) |
Pathways
• Olfactory transduction (KEGG: hsa04740)
• cGMP-PKG signaling pathway (KEGG: hsa04022)
• cAMP signaling pathway (KEGG: hsa04024)
• Ion channel transport (Reactome: R-HSA-983712)
Protein Summary
CNGA2 encodes a 664-amino acid protein that forms the pore-forming subunit of cyclic nucleotide-gated (CNG) channels. The protein contains six transmembrane domains, a cyclic nucleotide-binding domain (CNBD) in the C-terminus, and a pore loop region. It functions as a homotetramer or heterotetramer with other CNG subunits (e.g., CNGB1b) to form a nonselective cation channel permeable to Na+, K+, and Ca2+. Activation by cAMP or cGMP leads to membrane depolarization, critical for olfactory signal transduction. Post-translational modifications include N-glycosylation and phosphorylation, which modulate channel trafficking and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNGA2 Knockout HEK293 Cell Line | EDJ-KQ1801 | Human | 1260 | Details Get a Quote |
| CNGA2 Knockout HeLa Cell Line | EDJ-KQ52942 | Human | 1260 | Details Get a Quote |
| CNGA2 Knockout A-549 Cell Line | EDJ-KQ61408 | Human | 1260 | Details Get a Quote |
| CNGA2 Knockout HCT 116 Cell Line | EDJ-KQ69902 | Human | 1260 | Details Get a Quote |
