GRK6: G Protein-Coupled Receptor Kinase 6
A key regulator of GPCR desensitization and signaling in cancer and neurological disorders
Gene Information Card
| Symbol | GRK6 |
|---|---|
| Full Name | G protein-coupled receptor kinase 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 2870 ncbi.nlm.nih.gov/gene/2870 |
| Ensembl ID | ENSG00000113558 |
| UniProt ID | P43250 |
| OMIM ID | 600869 |
| HGNC ID | 4544 |
| Aliases | GPRK6, G protein-coupled receptor kinase 6 |
Description
GRK6 (G protein-coupled receptor kinase 6) encodes a member of the G protein-coupled receptor kinase (GRK) subfamily of the AGC (protein A, G, and C) serine/threonine kinases. GRK6 specifically phosphorylates agonist-occupied GPCRs, initiating receptor desensitization and internalization. It is widely expressed and implicated in dopaminergic signaling, immune cell chemotaxis, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | GRK6 overexpression or mutation alters GPCR signaling, promoting tumor growth and metastasis | COSMIC, ClinVar |
| Parkinson disease | GRK6 regulates dopamine receptor desensitization; altered expression linked to motor dysfunction | OMIM, NCBI |
| Immune disorders | GRK6 modulates chemokine receptor signaling in lymphocytes; dysregulation affects immune response | UniProt, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 10.1 | Medium |
| Liver | 6.7 | Low |
| Kidney | 9.4 | Medium |
| Spleen | 15.2 | High |
| Testis | 18.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.3 | High expression |
| K562 | 11.8 | Moderate expression |
| HeLa | 9.5 | Low expression |
| Jurkat | 16.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Trp) | Missense | <0.01% | Altered kinase activity; potential loss of function |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01% | Unknown effect; rare variant |
| c.1789_1791del (p.Phe597del) | Deletion | <0.01% | In-frame deletion; may affect C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
p.Arg338Trp reduces catalytic activity, impairing GPCR phosphorylation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GRK6.
Dominant Negative (DN)
Not established for GRK6.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor kinase activity | • protein serine/threonine kinase activity |
| • ATP binding | • receptor internalization |
| • signal transduction | • desensitization of G protein-coupled receptor signaling pathway |
Pathways
• GPCR downstream signaling
• Class A/1 (Rhodopsin-like receptors)
• Beta-arrestin-mediated desensitization
Protein Summary
GRK6 is a 576-amino acid serine/threonine kinase with an N-terminal RGS-like domain, a central catalytic kinase domain, and a C-terminal lipid-binding domain. It phosphorylates activated GPCRs, promoting beta-arrestin recruitment and receptor desensitization. GRK6 is highly expressed in brain, spleen, and testis, and its dysregulation is associated with cancer, Parkinson disease, and immune dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRK6 Knockout HEK293 Cell Line | EDJ-KQ4786 | Human | 2870 | Details Get a Quote |
| GRK6 Knockout A-549 Cell Line | EDJ-KQ26322 | Human | 2870 | Details Get a Quote |
| GRK6 Knockout HCT 116 Cell Line | EDJ-KQ27546 | Human | 2870 | Details Get a Quote |
| GRK6 Knockout HeLa Cell Line | EDJ-KQ27547 | Human | 2870 | Details Get a Quote |
| GRK6 Knockout HAP1 Cell Line | EDC08082 | Human | 2870 | Details Get a Quote |
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