CHRNA6
protein-codingcholinergic receptor nicotinic alpha 6 subunit, the group of Cholinergic receptors nicotinic subunits
Gene summary
This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. [provided by RefSeq, Dec 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.8 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 CHRNA6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004198.3. 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 | 3 | 4 | |||
| missense | 45 | 3 | 1 | 49 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 46 | 3 | 4 | 53 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004189.1 | 6 | MANE Select | |
| Ensembl | ENSP00000276410.3 | 6 | MANE Select | |
| RefSeq | NP_001186208.1 | 5 | Standard | |
| Ensembl | ENSP00000434659.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nicotine addiction - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Cholinergic synapse - Homo sapiens (human)
- Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics
- Nicotine Activity on Dopaminergic Neurons
Biological Process
- signal transduction
- chemical synaptic transmission
- synaptic transmission, cholinergic
- neuromuscular synaptic transmission
- regulation of dopamine secretion
Molecular Function
- extracellular ligand-gated ion channel activity
- protein binding
- acetylcholine receptor activity
- acetylcholine-gated cation-selective channel activity
- acetylcholine binding
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
- ENST00000276410
- Coding exons
- 6
- Length
- 43773
- Individuals with no LoFs
- 125553
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 192
- Defined
- 125746
- p
- 0.000768
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.125 | 262 | 268 | 0.979 | 0.0000136 | 3275 |
| Missense (PolyPhen) | 125 | 136.52 | 0.91559 | 1754 | ||
| Synonymous | 0.565 | 97 | 104 | 0.930 | 0.00000586 | 954 |
| Loss of Function | 1.06 | 14 | 19.0 | 0.737 | 9.06e-7 | 229 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00038 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.00093 | 0.00092 | rare |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.353
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 12.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.178
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |