GRK3
protein-codingG protein-coupled receptor kinase 3, the group of Pleckstrin homology domain containing|AGC family kinases
Gene summary
The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function. [provided by RefSeq, Jul 2008]
- ADRBK2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~164.6 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 GRK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005160.4. 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 | ||||
| missense | 6 | 6 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 11 | 0 | 1 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005151.2 | 21 | MANE Select | |
| Ensembl | ENSP00000317578.4 | 21 | MANE Select | |
| RefSeq | NP_001349707.1 | 18 | Standard | |
| Ensembl | ENSP00000393688.2 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| grk3 | Danio rerio | Structure: slow muscle cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutamatergic synapse - Homo sapiens (human)
- Endocytosis - Homo sapiens (human)
- Chemokine signaling pathway - Homo sapiens (human)
- Olfactory transduction - Homo sapiens (human)
- Morphine addiction - Homo sapiens (human)
Biological Process
- protein phosphorylation
- signal transduction
- G protein-coupled receptor signaling pathway
- receptor internalization
Molecular Function
- protein kinase activity
- G protein-coupled receptor kinase activity
- ATP binding
- beta-adrenergic receptor kinase activity
Cellular Component
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324198
- Coding exons
- 21
- Length
- 164446
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 51
- Defined
- 125748
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.63 | 234 | 378 | 0.619 | 0.0000208 | 4581 |
| Missense (PolyPhen) | 77 | 141.72 | 0.54333 | 1679 | ||
| Synonymous | 1.60 | 109 | 132 | 0.823 | 0.00000771 | 1186 |
| Loss of Function | 4.86 | 9 | 43.6 | 0.206 | 0.00000225 | 530 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000090 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.0013 | 0.0013 | notable |
| European (Non-Finnish) | 0.000098 | 0.000097 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors.;
Recessive Scores
- pRec
- 0.250
Intolerance Scores
- RVIS EVS
- -0.73
- RVIS percentile EVS
- 14.02
Essentials
- Essential (gene trap)
- N