Incidental Mutation 'F5426:Grk4'
ID584
Institutional Source Beutler Lab
Gene Symbol Grk4
Ensembl Gene ENSMUSG00000052783
Gene NameG protein-coupled receptor kinase 4
SynonymsGprk2l, A830025H08Rik
Accession Numbers

Genbank: NM_019497.2, NM_001080743.1

Is this an essential gene? Probably non essential (E-score: 0.169) question?
Stock #F5426 (G1) of strain 24G1
Quality Score
Status Validated
Chromosome5
Chromosomal Location34660379-34755305 bp(+) (GRCm38)
Type of Mutationsplice site
DNA Base Change (assembly) G to A at 34745159 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000001112 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001112]
Predicted Effect probably benign
Transcript: ENSMUST00000001112
SMART Domains Protein: ENSMUSP00000001112
Gene: ENSMUSG00000052783

DomainStartEndE-ValueType
RGS 51 171 1.61e-31 SMART
S_TKc 186 448 7.78e-85 SMART
S_TK_X 449 528 2.98e-3 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000134217
Predicted Effect noncoding transcript
Transcript: ENSMUST00000153323
Coding Region Coverage
  • 1x: 78.1%
  • 3x: 56.4%
Het Detection Efficiency35.2%
Validation Efficiency 91% (29/32)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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 the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
PHENOTYPE: Mice heterozygous for a knock-out allele are viable, fertile and overtly normal. [provided by MGI curators]
Allele List at MGI

All alleles(4) : Targeted, knock-out(1) Targeted, other(1) Gene trapped(2)

Other mutations in this stock
Total: 10 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Cdk5rap2 A T 4: 70,254,803 V1344E probably benign Het
D16Ertd472e C T 16: 78,548,001 C73Y probably damaging Het
Odc1 G A 12: 17,549,423 probably null Het
Olfr110 A C 17: 37,499,536 K295T probably damaging Het
Prss12 T C 3: 123,506,472 V744A probably damaging Het
Pudp A T 18: 50,568,541 N40K probably benign Het
Rab30 T C 7: 92,829,668 I107T possibly damaging Het
Ryr3 T A 2: 112,766,338 probably benign Het
Sh2d1b1 C A 1: 170,279,781 probably null Het
Tmc5 T A 7: 118,623,323 V82D probably benign Het
Other mutations in Grk4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00509:Grk4 APN 5 34716290 missense probably damaging 0.99
IGL00574:Grk4 APN 5 34694818 missense probably benign 0.00
IGL02127:Grk4 APN 5 34710186 missense probably benign 0.00
IGL02191:Grk4 APN 5 34755189 missense probably benign 0.27
IGL02227:Grk4 APN 5 34694782 missense probably benign 0.06
IGL03152:Grk4 APN 5 34745357 missense probably damaging 1.00
IGL03214:Grk4 APN 5 34752209 missense probably benign
R0110:Grk4 UTSW 5 34716213 missense probably damaging 0.97
R0469:Grk4 UTSW 5 34716213 missense probably damaging 0.97
R0671:Grk4 UTSW 5 34748267 missense probably benign 0.04
R1466:Grk4 UTSW 5 34694750 missense probably benign 0.02
R1466:Grk4 UTSW 5 34694750 missense probably benign 0.02
R1584:Grk4 UTSW 5 34694750 missense probably benign 0.02
R1605:Grk4 UTSW 5 34674557 missense probably damaging 0.98
R1607:Grk4 UTSW 5 34731538 missense probably benign 0.01
R1903:Grk4 UTSW 5 34676187 splice site probably null
R2352:Grk4 UTSW 5 34669176 missense probably benign 0.04
R4561:Grk4 UTSW 5 34694813 missense probably benign 0.00
R4580:Grk4 UTSW 5 34660981 missense probably damaging 1.00
R4807:Grk4 UTSW 5 34752208 missense probably benign
R5412:Grk4 UTSW 5 34745268 missense probably benign 0.00
R5905:Grk4 UTSW 5 34711730 missense probably damaging 1.00
R6360:Grk4 UTSW 5 34674537 missense probably damaging 1.00
R6604:Grk4 UTSW 5 34719864 missense probably damaging 1.00
R6865:Grk4 UTSW 5 34731550 missense probably damaging 1.00
R7265:Grk4 UTSW 5 34716264 missense probably damaging 0.96
R7394:Grk4 UTSW 5 34751618 missense probably benign
X0064:Grk4 UTSW 5 34719884 missense possibly damaging 0.76
Nature of Mutation

DNA sequencing using the SOLiD technique identified a G to A transition at base pair 35087808 in the Genbank genomic region NC_000071 for the Grk4 gene on chromosome 5 (TGTTATGTAG ->TGTTATATAG). Multiple transcripts of the Grk4 gene are displayed on Ensembl and Vega. The mutation is located within intron 11 from the ATG exon, four nucleotides to the previous exon. The Grk4 gene contains 17 total exons using Genbank record NM_019497.2. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Grk4 gene encodes a 574 amino acid  kinase that specifically phosphorylates the activated forms of G protein-coupled receptors (GPCRs). GPCR kinases are a family of serine/threonine kinases that appear to play a role in receptor desensitization. They increase the ability of GPCRs to interact with arrestins, which then blocks further activation of signal transduction pathways. The protein contains an RGS (regulator of G protein signaling) domain at residues 51-171, a kinase domain at residues 186-488, and an AGC kinase C-terminal domain at residues 449-514 (Uniprot O70291). In human essential hypertension, single nucleotide polymorphisms (SNPs) of the GRK4-gamma isoform increases GRK activity and causes the serine phosphorylation and uncoupling of the D1 GPCR receptor from its G protein/effector enzyme complex in the renal proximal tubule.

Posted On2011-03-09