GNAT3
protein-codingG protein subunit alpha transducin 3, the group of G protein subunits alpha, group i
Gene summary
Sweet, bitter, and umami tastes are transmitted from taste receptors by a specific guanine nucleotide binding protein. The protein encoded by this gene is the alpha subunit of this heterotrimeric G protein, which is found not only in the oral epithelium but also in gut tissues. Variations in this gene have been linked to metabolic syndrome. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.4 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 GNAT3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001102386.3. 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 | 1 | ||||
| missense | 47 | 47 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 48 | 0 | 1 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001095856.1 | 8 | MANE Select | |
| Ensembl | ENSP00000381339.3 | 8 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Carbohydrate digestion and absorption - Homo sapiens (human)
- Taste transduction - Homo sapiens (human)
- Signaling by GPCR
- Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
- Signal Transduction
Biological Process
- detection of chemical stimulus involved in sensory perception of bitter taste
- protein folding
- G protein-coupled receptor signaling pathway
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Molecular Function
- G protein-coupled receptor binding
- GTPase activity
- GTP binding
- G-protein beta/gamma-subunit complex binding
- metal ion binding
Cellular Component
- acrosomal vesicle
- photoreceptor outer segment
- photoreceptor inner segment
- heterotrimeric G-protein complex
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398291
- Coding exons
- 8
- Length
- 53350
- Individuals with no LoFs
- 124838
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 94
- Defined
- 124933
- p
- 0.000380
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.257 | 157 | 166 | 0.944 | 0.00000776 | 2328 |
| Missense (PolyPhen) | 62 | 70.714 | 0.87677 | 1034 | ||
| Synonymous | 0.0858 | 58 | 58.8 | 0.986 | 0.00000285 | 624 |
| Loss of Function | 1.49 | 10 | 16.5 | 0.605 | 8.70e-7 | 227 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00027 | 0.00026 | rare |
| Latino/Admixed American | 0.000091 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00028 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00067 | 0.00063 | rare |
| South Asian | 0.00030 | 0.00026 | rare |
| Other | 0.00070 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide- 1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity. {ECO:0000269|PubMed:11917125, ECO:0000269|PubMed:17724330}.;
Intolerance Scores
- LoFtool
- 0.431
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.677
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |