GRK1

Chr 13

G protein-coupled receptor kinase 1

Also known as: GPRK1, RHOK, RK

NCBI Gene: 6011 ENSG00000185974 UniProt: Q15835

The protein is a retina-specific kinase that phosphorylates rhodopsin to terminate phototransduction signaling, which is essential for scotopic vision and rapid adaptation to changes in illumination. Mutations cause Oguchi disease-2, a form of congenital stationary night blindness with autosomal recessive inheritance. The gene shows low constraint against loss-of-function variants, consistent with its recessive disease pattern.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates rhodopsin and initiates its deactivation. Defects in GRK1 are known to cause Oguchi disease 2 (also known as stationary night blindness Oguchi type-2). [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNight blindness, congenital stationary, Oguchi type 2

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Oguchi disease · AR · ClinGen 2021

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.22

OE 0.49 (0.31–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.43Z-score

OE missense 0.93 (0.85–1.02)

314 obs / 336.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.31–0.82)

0≤0.351.4

Missense OE?0.93 (0.85–1.02)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 11 / 22.3Missense obs/exp: 314 / 336.3Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in GRK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

760 rare PASS variants

Rare truncating (LoF)

1 in 660

95 rare PASS variants

Rare synonymous (reference)

1 in 96

346 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GRK1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 71	1 in 770
South Asian	~43k	1 in 48	1 in 520
Remaining (unassigned)	~30k	1 in 41	1 in 530
European (Finnish)	~27k	1 in 240	≈ 1 in 7,200
Admixed American	~22k	1 in 45	1 in 1,600
African / African American	~21k	1 in 64	1 in 1,600
East Asian	~20k	1 in 78	1 in 680
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 72	1 in 470

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 7 coding exons well covered in gnomAD exomes; exons 3, 4 poorly covered. Genomes: 6 of 7 (exon 4 below).? see exons ↓