GRK6

G protein-coupled receptor kinase 6, the group of AGC family kinases

Basic information

Region (hg38): 5:177403204-177442901

Previous symbols: [ "GPRK6" ]

Links

ENSG00000198055 ∙ NCBI:2870 ∙ OMIM:600869 ∙ HGNC:4545 ∙ Uniprot:P43250 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRK6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRK6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			17	2		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	17	2	0

Variants in GRK6

This is a list of pathogenic ClinVar variants found in the GRK6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-177403242-A-G			Benign (Nov 11, 2022)
5-177403255-C-G		Hereditary angioedema type 3	Uncertain significance (-)
5-177403267-G-T			Likely benign (Jul 30, 2022)
5-177403267-GC-G		Factor XII deficiency disease	Likely pathogenic (-)
5-177403293-T-C			Uncertain significance (Nov 01, 2022)
5-177403300-G-C			Likely benign (Dec 01, 2023)
5-177403311-C-T		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
5-177403323-G-A		Factor XII deficiency disease	Uncertain significance (Mar 29, 2024)
5-177403325-A-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
5-177403348-C-A			Benign (Feb 08, 2023)
5-177403350-A-G			Uncertain significance (Dec 20, 2023)
5-177403357-C-T			Likely benign (Oct 26, 2023)
5-177403367-C-T		Inborn genetic diseases	Uncertain significance (Dec 02, 2021)
5-177403432-G-A			Benign (Nov 11, 2018)
5-177403477-G-C		Factor XII deficiency disease • Hereditary angioedema type 3	Conflicting classifications of pathogenicity (Jul 01, 2023)
5-177403514-C-T			Uncertain significance (Sep 12, 2022)
5-177403525-C-T			Uncertain significance (Nov 24, 2023)
5-177403526-G-A		Hereditary angioneurotic edema • Factor XII deficiency disease • Nephrolithiasis/osteoporosis, hypophosphatemic • Hereditary angioedema type 3 • F12-related disorder	Benign/Likely benign (Jan 22, 2024)
5-177403539-G-A			Likely benign (Jul 13, 2023)
5-177403554-C-T			Likely benign (May 12, 2022)
5-177403569-G-A		Nephrolithiasis/osteoporosis, hypophosphatemic • Factor XII deficiency disease • Hereditary angioneurotic edema • Hereditary angioedema type 3 • F12-related disorder	Benign/Likely benign (Dec 01, 2023)
5-177403596-C-G		Nephrolithiasis/osteoporosis, hypophosphatemic • Hereditary angioneurotic edema • Factor XII deficiency disease • Hereditary angioedema type 3 • Factor XII deficiency disease;Hereditary angioedema type 3 • F12-related disorder	Benign/Likely benign (Nov 17, 2023)
5-177403612-G-A		Thrombus	Uncertain significance (-)
5-177403621-CG-C		F12-related disorder	Likely benign (Jun 06, 2019)
5-177403621-C-CG		F12-related disorder	Benign/Likely benign (Nov 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRK6	protein_coding	protein_coding	ENST00000528793	16	39698

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000487	0.999	125732	0	12	125744	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.81	234	390	0.600	0.0000266	3824
Missense in Polyphen		70	160.75	0.43547		1671
Synonymous	0.165	159	162	0.983	0.0000113	1137
Loss of Function	3.50	12	34.1	0.352	0.00000163	375

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000919	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.0000632	0.0000615
Middle Eastern	0.0000546	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor: LRP6 during Wnt signaling (in vitro). {ECO:0000250, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20048153}.
• Pathway: Endocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Morphine addiction - Homo sapiens (human);HH-Ncore;Follicle Stimulating Hormone (FSH) signaling pathway;Corticotropin-releasing hormone signaling pathway;Myometrial Relaxation and Contraction Pathways;Chemokine signaling pathway;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;CRH;IL-7 signaling;CXCR4-mediated signaling events;JAK STAT pathway and regulation;EPO signaling;VEGF;GPCR downstream signalling;FSH (Consensus)

Recessive Scores

• pRec: 0.207

Intolerance Scores

• loftool: 0.549
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• pHI: 0.506
• hipred: Y
• hipred_score: 0.704
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Grk6
• Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype; immune system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein phosphorylation;G protein-coupled receptor signaling pathway;regulation of G protein-coupled receptor signaling pathway;Wnt signaling pathway
• Cellular component: plasma membrane;membrane
• Molecular function: G protein-coupled receptor kinase activity;protein binding;ATP binding;beta-adrenergic receptor kinase activity