GRK2

G protein-coupled receptor kinase 2, the group of AGC family kinases|Pleckstrin homology domain containing

Basic information

Region (hg38): 11:67266473-67286556

Previous symbols: [ "ADRBK1" ]

Links

ENSG00000173020 ∙ NCBI:156 ∙ OMIM:109635 ∙ HGNC:289 ∙ Uniprot:P25098 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Jeune syndrome (Moderate), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRK2 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				2	2	4
missense			4	1		5
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	4	3	2

Variants in GRK2

This is a list of pathogenic ClinVar variants found in the GRK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-67279515-C-T		not specified	Uncertain significance (Oct 06, 2021)
11-67279866-C-T		Jeune thoracic dystrophy	Pathogenic (-)
11-67280784-G-A		Jeune thoracic dystrophy	Likely pathogenic (-)
11-67282482-C-T			Likely benign (Jan 01, 2023)
11-67282535-C-T			Likely benign (May 13, 2018)
11-67283204-G-A		not specified	Uncertain significance (Jul 26, 2021)
11-67283721-AAG-A		Jeune thoracic dystrophy	Likely pathogenic (-)
11-67283899-G-A		not specified	Uncertain significance (Oct 29, 2021)
11-67284206-T-A			Likely benign (Aug 16, 2018)
11-67284302-C-T		not specified	Uncertain significance (Aug 02, 2021)
11-67284851-C-T			Benign (Jul 31, 2018)
11-67285185-C-T			Likely benign (Jan 01, 2023)
11-67285449-G-A			Benign (Jul 06, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRK2	protein_coding	protein_coding	ENST00000308595	21	20147

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000203	125654	0	4	125658	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.22	254	445	0.571	0.0000306	4536
Missense in Polyphen		73	174.8	0.41762		1743
Synonymous	-1.03	205	187	1.10	0.0000136	1269
Loss of Function	5.70	3	43.7	0.0687	0.00000224	479

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925, PubMed:19715378). Positively regulates ciliary smoothened (SMO)- dependent Hedgehog (Hh) signaling pathway by faciltating the trafficking of SMO into the cilium and the stimulation of SMO activity (By similarity). {ECO:0000250|UniProtKB:P21146, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:19715378}.
• Pathway: 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);Hedgehog signaling pathway - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Chemokine signaling pathway;Hedgehog Signaling Pathway;Hedgehog Signaling Pathway;Signaling by GPCR;Signal Transduction;Vesicle-mediated transport;regulation of ck1/cdk5 by type 1 glutamate receptors;role of -arrestins in the activation and targeting of map kinases;Membrane Trafficking;Hedgehog;Activation of SMO;Hedgehog;G alpha (s) signalling events;Calmodulin induced events;CaM pathway;roles of arrestin dependent recruitment of src kinases in gpcr signaling;IL-7 signaling;Hedgehog ,on, state;Signaling by Hedgehog;Clathrin-mediated endocytosis;EGFR1;Signaling events mediated by HDAC Class II;CXCR4-mediated signaling events;-arrestins in gpcr desensitization;DAG and IP3 signaling;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;EPO signaling;Cargo recognition for clathrin-mediated endocytosis;Ca-dependent events;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;VEGF;G alpha (q) signalling events;GPCR downstream signalling;Intracellular signaling by second messengers;IL8- and CXCR1-mediated signaling events;Signaling events mediated by the Hedgehog family (Consensus)

Recessive Scores

• pRec: 0.452

Intolerance Scores

• rvis_EVS: -1.16
• rvis_percentile_EVS: 6.17

Haploinsufficiency Scores

• pHI: 0.655
• hipred: Y
• hipred_score: 0.793
• ghis: 0.701

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Grk2
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; immune system phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: desensitization of G protein-coupled receptor signaling pathway;negative regulation of the force of heart contraction by chemical signal;G protein-coupled receptor signaling pathway;G protein-coupled acetylcholine receptor signaling pathway;tachykinin receptor signaling pathway;heart development;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;viral genome replication;receptor internalization;positive regulation of catecholamine secretion;negative regulation of striated muscle contraction;viral entry into host cell;cardiac muscle contraction
• Cellular component: cytoplasm;cytosol;plasma membrane;cilium;membrane
• Molecular function: protein kinase activity;G protein-coupled receptor kinase activity;protein binding;ATP binding;alpha-2A adrenergic receptor binding;Edg-2 lysophosphatidic acid receptor binding;beta-adrenergic receptor kinase activity