GRK1

G protein-coupled receptor kinase 1, the group of AGC family kinases

Basic information

Region (hg38): 13:113667218-113737736

Previous symbols: [ "RHOK" ]

Links

ENSG00000185974 ∙ NCBI:6011 ∙ OMIM:180381 ∙ HGNC:10013 ∙ Uniprot:Q15835 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Oguchi disease (Supportive), mode of inheritance: AR
• Oguchi disease-2 (Definitive), mode of inheritance: AR
• Oguchi disease (Definitive), mode of inheritance: AR
• Oguchi disease-2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oguchi disease 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	14281981; 9020843; 17070587; 17765441; 19753316; 22959359

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRK1 gene.

• Inborn genetic diseases (16 variants)
• not provided (11 variants)
• Oguchi disease-2 (3 variants)
• not specified (1 variants)
• Oguchi disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRK1 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				1		1
missense	1		18	3		22
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					4	4
Total	1	1	18	4	4

Highest pathogenic variant AF is 0.0000396

Variants in GRK1

This is a list of pathogenic ClinVar variants found in the GRK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-113667441-C-T		Oguchi disease-2	Likely pathogenic (Dec 19, 2019)
13-113667478-G-A		Oguchi disease	Uncertain significance (Apr 27, 2019)
13-113667525-TGTGA-T		Oguchi disease-2	Likely pathogenic (Feb 20, 2019)
13-113667528-G-C		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
13-113667537-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
13-113667548-C-T		Oguchi disease-2 • not specified • GRK1-related disorder	Benign/Likely benign (Oct 16, 2019)
13-113667564-A-C		Inborn genetic diseases	Uncertain significance (Feb 04, 2022)
13-113667620-G-A		GRK1-related disorder	Likely benign (Aug 12, 2019)
13-113667650-C-T		GRK1-related disorder	Likely benign (Mar 25, 2019)
13-113667675-A-C		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
13-113667683-C-G		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
13-113667748-T-C		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
13-113667754-G-A		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
13-113667781-C-T		Inborn genetic diseases	Likely benign (May 09, 2022)
13-113667798-C-A		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
13-113667816-G-T		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
13-113667817-G-C		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
13-113667849-G-T		Inborn genetic diseases	Uncertain significance (Feb 24, 2022)
13-113667850-C-T		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
13-113667853-A-T		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
13-113667856-T-C		Oguchi disease-2	Likely pathogenic (Dec 17, 2019)
13-113667889-GCCTGTACTT-G		Oguchi disease-2	Likely pathogenic (Sep 01, 2022)
13-113667958-T-A		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
13-113667981-G-C		Oguchi disease-2	Likely pathogenic (Feb 20, 2019)
13-113668000-C-A		Oguchi disease-2	Likely pathogenic (Feb 20, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRK1	protein_coding	protein_coding	ENST00000335678	7	119239

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000307	0.987	124632	1	41	124674	0.000168

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.432	314	336	0.934	0.0000210	3702
Missense in Polyphen		125	149.79	0.83448		1572
Synonymous	0.275	154	158	0.972	0.0000116	1088
Loss of Function	2.22	11	22.3	0.493	0.00000111	254

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000392	0.000380
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000545	0.0000531
Middle Eastern	0.000111	0.000111
South Asian	0.000866	0.000817
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade. This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination. {ECO:0000269|PubMed:15946941}.
• Disease: DISEASE: Night blindness, congenital stationary, Oguchi type 2 (CSNBO2) [MIM:613411]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is associated with fundus discoloration and abnormally slow dark adaptation. {ECO:0000269|PubMed:17070587, ECO:0000269|PubMed:9020843}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Phototransduction - Homo sapiens (human);Chemokine signaling pathway;Signaling by GPCR;Signal Transduction;visual signal transduction;Visual signal transduction: Rods;G alpha (i) signalling events;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR downstream signalling;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.180

Haploinsufficiency Scores

• pHI: 0.178
• hipred: N
• hipred_score: 0.322
• ghis: 0.461

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.809

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grk1
• Phenotype: cellular phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: visual perception;regulation of G protein-coupled receptor signaling pathway;rhodopsin mediated signaling pathway;regulation of rhodopsin mediated signaling pathway;protein autophosphorylation
• Cellular component: photoreceptor disc membrane
• Molecular function: protein kinase activity;G protein-coupled receptor kinase activity;ATP binding;rhodopsin kinase activity