CHRNA9
protein-codingcholinergic receptor nicotinic alpha 9 subunit, the group of Cholinergic receptors nicotinic subunits
Gene summary
This gene is a member of the ligand-gated ionic channel family and nicotinic acetylcholine receptor gene superfamily. It encodes a plasma membrane protein that forms homo- or hetero-oligomeric divalent cation channels. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea. [provided by RefSeq, Feb 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.9 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 CHRNA9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017581.4. 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 | 2 | 2 | ||||
| missense | 73 | 4 | 77 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 73 | 6 | 0 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060051.2 | 5 | MANE Select | |
| Ensembl | ENSP00000312663.2 | 5 | MANE Select | |
| Ensembl | ENSP00000806291.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Neuronal System
- Neurotransmitter receptors and postsynaptic signal transmission
- Transmission across Chemical Synapses
- Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
Biological Process
- signal transduction
- positive regulation of cytosolic calcium ion concentration
- chemical synaptic transmission
- ion transmembrane transport
- regulation of membrane potential
Molecular Function
- transmembrane signaling receptor activity
- extracellular ligand-gated ion channel activity
- calcium channel activity
- protein binding
- acetylcholine-gated cation-selective channel activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- acetylcholine-gated channel complex
- cell junction
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310169
- Coding exons
- 5
- Length
- 19889
- Individuals with no LoFs
- 125642
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 105
- Defined
- 125747
- p
- 0.000418
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.102 | 276 | 271 | 1.02 | 0.0000154 | 3180 |
| Missense (PolyPhen) | 143 | 133.87 | 1.0682 | 1602 | ||
| Synonymous | -0.379 | 117 | 112 | 1.05 | 0.00000720 | 916 |
| Loss of Function | 1.63 | 11 | 18.6 | 0.592 | 9.66e-7 | 215 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00043 | 0.00043 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00052 | 0.00052 | rare |
| South Asian | 0.00052 | 0.00052 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the opening of an ion-conducting channel across the plasma membrane (PubMed:11752216, PubMed:25282151). The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane (PubMed:11752216, PubMed:25282151). In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion (PubMed:11021840). {ECO:0000269|PubMed:11021840, ECO:0000269|PubMed:11752216, ECO:0000269|PubMed:25282151, ECO:0000305}.;
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- LoFtool
- 0.300
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.103
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |