CNGA4
protein-codingcyclic nucleotide gated channel subunit alpha 4, the group of Cyclic nucleotide gated channels
Gene summary
CNGA4 is a modulatory subunit of vertebrate cyclic nucleotide-gated membrane channels that transduce odorant signals (Munger et al., 2001 [PubMed 11739959]).[supplied by OMIM, Mar 2008]
- CNCA2
- CNGB2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CNGA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001037329.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 92 | 3 | 2 | 97 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 93 | 5 | 2 | 100 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001032406.1 | 6 | MANE Select | |
| Ensembl | ENSP00000369268.2 | 6 | MANE Select | |
| Ensembl | ENSP00000433399.1 | 4 | Standard | |
| Ensembl | ENSP00000542264.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- cAMP signaling pathway - Homo sapiens (human)
- Olfactory transduction - Homo sapiens (human)
- NO-cGMP-PKG mediated Neuroprotection
- VxPx cargo-targeting to cilium
- Cargo trafficking to the periciliary membrane
Biological Process
- sensory perception of smell
- response to stimulus
- cation transmembrane transport
Molecular Function
- intracellular cAMP-activated cation channel activity
- intracellular cGMP-activated cation channel activity
- cAMP binding
- cGMP binding
Cellular Component
- Golgi membrane
- integral component of membrane
- Golgi-associated vesicle membrane
- ciliary membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379936
- Coding exons
- 6
- Length
- 9665
- Individuals with no LoFs
- 125494
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 253
- Defined
- 125748
- p
- 0.00101
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0116 | 348 | 349 | 0.998 | 0.0000235 | 3728 |
| Missense (PolyPhen) | 116 | 128.26 | 0.90442 | 1405 | ||
| Synonymous | 1.03 | 129 | 145 | 0.891 | 0.00000958 | 1192 |
| Loss of Function | 1.71 | 14 | 22.8 | 0.614 | 0.00000126 | 241 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00064 | 0.00064 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0011 | 0.0011 | notable |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00099 | 0.00098 | rare |
| South Asian | 0.0028 | 0.0028 | notable |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Second messenger, cAMP, causes the opening of cation- selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.153
- RVIS EVS
- 0.18
- RVIS percentile EVS
- 66.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.224
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |