CHRM5
protein-codingcholinergic receptor muscarinic 5, the group of Cholinergic receptors muscarinic
Gene summary
The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~99.0 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 CHRM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012125.4. 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 | 2 | |||
| missense | 55 | 3 | 1 | 59 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 56 | 3 | 2 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036257.1 | 1 | MANE Select | |
| Ensembl | ENSP00000372750.5 | 1 | MANE Select | |
| RefSeq | NP_001307846.1 | 1 | Standard | |
| Ensembl | ENSP00000453745.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Cholinergic synapse - Homo sapiens (human)
- GPCRs, Class A Rhodopsin-like
Biological Process
- gastric acid secretion
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
- G protein-coupled acetylcholine receptor signaling pathway
Molecular Function
- phosphatidylinositol phospholipase C activity
- G protein-coupled receptor activity
- G protein-coupled serotonin receptor activity
- G protein-coupled acetylcholine receptor activity
- neurotransmitter receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell junction
- dendrite
- postsynaptic membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000383263
- Coding exons
- 1
- Length
- 96371
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125747
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.20 | 235 | 293 | 0.802 | 0.0000158 | 3475 |
| Missense (PolyPhen) | 83 | 134.93 | 0.61513 | 1651 | ||
| Synonymous | -0.125 | 114 | 112 | 1.01 | 0.00000571 | 1088 |
| Loss of Function | 2.36 | 7 | 17.7 | 0.395 | 0.00000118 | 188 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.;
Recessive Scores
- pRec
- 0.0829
Intolerance Scores
- LoFtool
- 0.586
- RVIS EVS
- 0.38
- RVIS percentile EVS
- 75.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.185
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |