GNAL
protein-codingG protein subunit alpha L, the group of G protein subunits alpha, group s
Gene summary
This gene encodes a stimulatory G protein alpha subunit which mediates odorant signaling in the olfactory epithelium. This protein couples dopamine type 1 receptors and adenosine A2A receptors and is widely expressed in the central nervous system. Mutations in this gene have been associated with dystonia 25 and this gene is located in a susceptibility region for bipolar disorder and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~196.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014033
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014033
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0014033
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014033
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014033
Submitter: Genomics England PanelApp
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GNAL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182978.4. 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 | 6 | 35 | 6 | 47 | ||
| missense | 3 | 5 | 76 | 3 | 87 | |
| nonsense | 3 | 2 | 5 | |||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 2 | 2 | 4 | |||
| Total | 10 | 10 | 84 | 38 | 6 | 148 |
Highest pathogenic variant AF is 0.0000020915572
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_892023.1 | 12 | MANE Select | |
| Ensembl | ENSP00000334051.5 | 12 | MANE Select | |
| RefSeq | NP_001135811.1 | 12 | Standard | |
| RefSeq | NP_001248372.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Dopaminergic synapse - Homo sapiens (human)
- Amoebiasis - Homo sapiens (human)
- Chagas disease (American trypanosomiasis) - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Parkinson,s disease - Homo sapiens (human)
Biological Process
- signal transduction
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- sensory perception of smell
Molecular Function
- G protein-coupled receptor binding
- GTPase activity
- GTP binding
- G-protein beta/gamma-subunit complex binding
- metal ion binding
Cellular Component
- heterotrimeric G-protein complex
- plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334049
- Coding exons
- 12
- Length
- 196730
- Individuals with no LoFs
- 125048
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125049
- p
- 0.00000400
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.34 | 87 | 229 | 0.380 | 0.0000127 | 2995 |
| Missense (PolyPhen) | 23 | 123.55 | 0.18616 | 1430 | ||
| Synonymous | 0.466 | 83 | 88.6 | 0.937 | 0.00000541 | 861 |
| Loss of Function | 4.25 | 1 | 23.0 | 0.0435 | 0.00000121 | 276 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(olf) alpha mediates signal transduction within the olfactory neuroepithelium and the basal ganglia. May be involved in some aspect of visual transduction, and in mediating the effect of one or more hormones/neurotransmitters.;
Recessive Scores
- pRec
- 0.189
Intolerance Scores
- LoFtool
- 0.0256
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.743
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |