CNGA4: Cyclic Nucleotide Gated Channel Subunit Alpha 4
A key component of olfactory signal transduction and cyclic nucleotide-gated ion channels.
Gene Information Card
| Symbol | CNGA4 |
|---|---|
| Full Name | Cyclic Nucleotide Gated Channel Subunit Alpha 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 1262 ncbi.nlm.nih.gov/gene/1262 |
| Ensembl ID | ENSG00000132259 |
| UniProt ID | Q8IV77 |
| OMIM ID | 600638 |
| HGNC ID | 2150 |
| Aliases | CNG4, CNG-4, OCNC2, OCNCb |
Description
CNGA4 encodes the alpha-4 subunit of cyclic nucleotide-gated (CNG) channels, which are nonselective cation channels activated by cyclic nucleotides such as cAMP and cGMP. This subunit is primarily expressed in olfactory sensory neurons, where it forms heteromeric channels essential for olfactory signal transduction. CNGA4 modulates channel gating and contributes to the adaptation and sensitivity of olfactory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinitis Pigmentosa (rare association) | Altered CNG channel function in photoreceptors may contribute to retinal degeneration. | ClinVar; limited evidence; case reports. |
| Olfactory dysfunction | Loss-of-function mutations in CNGA4 impair olfactory signal transduction, leading to anosmia or hyposmia. | OMIM; functional studies in animal models. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Olfactory mucosa | 12.5 | High |
| Testis | 3.2 | Low |
| Brain (cerebellum) | 1.8 | Low |
| Retina | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Olfactory sensory neurons | 15.0 | Primary cell type |
| HEK293 | 0.5 | Overexpression studies |
| Retinal pigment epithelium | 0.8 | Low endogenous |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.1546G>A (p.Gly516Arg) | Missense | <0.01% | Altered channel gating; reduced cAMP sensitivity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or unstable protein, impairing olfactory signal transduction.
Gain of Function (GOF)
Not reported for CNGA4.
Dominant Negative (DN)
Missense mutations that disrupt heteromeric channel assembly may exert dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • ion channel activity (GO:0005216) | • voltage-gated potassium channel complex (GO:0008076) |
| • protein binding (GO:0005515) | • integral component of membrane (GO:0016021) |
| • cAMP binding (GO:0030552) | • cGMP binding (GO:0030553) |
| • sensory perception of chemical stimulus (GO:0007606) | • sensory perception of smell (GO:0007608) |
Pathways
• Olfactory transduction (KEGG: hsa04740)
• Cyclic nucleotide-gated channel signaling
Protein Summary
CNGA4 is a 575-amino acid protein with six transmembrane domains, a pore-forming region, and a cyclic nucleotide-binding domain (CNBD) in the C-terminus. It functions as a subunit of heterotetrameric CNG channels, typically co-assembling with CNGA2 and CNGB1b in olfactory neurons. The protein is essential for channel gating by cyclic nucleotides and mediates calcium influx, leading to depolarization and action potential generation in response to odorants.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNGA4 Knockout HEK293 Cell Line | EDJ-KQ1803 | Human | 1262 | Details Get a Quote |
| CNGA4 Knockout HeLa Cell Line | EDJ-KQ52944 | Human | 1262 | Details Get a Quote |
| CNGA4 Knockout A-549 Cell Line | EDJ-KQ61410 | Human | 1262 | Details Get a Quote |
| CNGA4 Knockout HCT 116 Cell Line | EDJ-KQ69904 | Human | 1262 | Details Get a Quote |
