GRK4

G protein-coupled receptor kinase 4, the group of AGC family kinases

Basic information

Region (hg38): 4:2963570-3040760

Previous symbols: [ "GPRK2L" ]

Links

ENSG00000125388 ∙ NCBI:2868 ∙ OMIM:137026 ∙ HGNC:4543 ∙ Uniprot:P32298 ∙ 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 GRK4 gene.

• Inborn genetic diseases (26 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRK4 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	1	3
missense			26			26
nonsense					1	1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	2	2

Variants in GRK4

This is a list of pathogenic ClinVar variants found in the GRK4 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-2984569-C-A		not specified	Uncertain significance (Sep 14, 2021)
4-2984578-A-C		not specified	Uncertain significance (Dec 16, 2023)
4-2988771-C-T		not specified	Uncertain significance (May 18, 2022)
4-2988819-A-G		not specified	Uncertain significance (Jul 19, 2022)
4-2988829-T-C		not specified	Uncertain significance (May 26, 2023)
4-2992275-A-C			Likely benign (Dec 01, 2022)
4-2992276-G-A		not specified	Uncertain significance (Jul 30, 2023)
4-3004299-G-T		not specified	Uncertain significance (Aug 19, 2023)
4-3004303-C-T		not specified	Uncertain significance (Jul 09, 2021)
4-3007744-A-G		not specified	Uncertain significance (Oct 29, 2021)
4-3007764-C-G		not specified	Uncertain significance (Aug 04, 2023)
4-3007809-C-T			Benign (Oct 30, 2018)
4-3009655-G-A		not specified	Uncertain significance (May 25, 2022)
4-3009659-C-G		not specified	Uncertain significance (Jun 29, 2023)
4-3013694-G-A		not specified	Uncertain significance (Aug 30, 2021)
4-3013731-G-T		not specified	Uncertain significance (Jun 28, 2023)
4-3013764-G-A		not specified	Uncertain significance (May 31, 2023)
4-3013815-A-G		not specified	Uncertain significance (Jul 19, 2022)
4-3019664-A-C		not specified	Uncertain significance (Aug 12, 2021)
4-3019675-C-G		not specified	Uncertain significance (Dec 08, 2023)
4-3019722-C-T		not specified	Uncertain significance (Apr 27, 2022)
4-3019746-G-A		not specified	Uncertain significance (Dec 17, 2023)
4-3019748-C-T			Benign (Mar 29, 2018)
4-3019800-G-A		not specified	Uncertain significance (Sep 16, 2021)
4-3022431-A-C		not specified	Uncertain significance (Sep 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRK4	protein_coding	protein_coding	ENST00000398052	16	77140

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.63e-15	0.172	125573	2	173	125748	0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.580	344	315	1.09	0.0000160	3796
Missense in Polyphen		132	125.05	1.0556		1518
Synonymous	-0.861	132	120	1.10	0.00000674	1016
Loss of Function	1.15	27	34.3	0.788	0.00000160	439

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00102	0.00101
Ashkenazi Jewish	0.00450	0.00437
East Asian	0.000381	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000380	0.000378
Middle Eastern	0.000381	0.000381
South Asian	0.00146	0.00141
Other	0.00132	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2. {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8626439}.
• Pathway: Endocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;Chemokine signaling pathway;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;attenuation of gpcr signaling;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;G alpha (i) signalling events;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;VEGF;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.965
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.87

Haploinsufficiency Scores

• pHI: 0.466
• hipred: N
• hipred_score: 0.218
• ghis: 0.452

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Grk4
• Phenotype: normal phenotype

Gene ontology

• Biological process: G protein-coupled receptor internalization;protein phosphorylation;signal transduction;regulation of G protein-coupled receptor signaling pathway;regulation of rhodopsin mediated signaling pathway;receptor internalization
• Cellular component: cytosol;cell cortex;dendrite;neuronal cell body;photoreceptor disc membrane
• Molecular function: G protein-coupled receptor kinase activity;ATP binding;rhodopsin kinase activity