Incidental Mutation 'R2021:Grk2'
ID 224052
Institutional Source Beutler Lab
Gene Symbol Grk2
Ensembl Gene ENSMUSG00000024858
Gene Name G protein-coupled receptor kinase 2
Synonyms betaARK1, Bark-1, Adrbk-1, beta ARK1, Adrbk1, beta-AR kinase-1, beta-adrenergic receptor kinase-1, beta ARK
MMRRC Submission 040030-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2021 (G1)
Quality Score 225
Status Not validated
Chromosome 19
Chromosomal Location 4336029-4356250 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 4340698 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 254 (I254F)
Ref Sequence ENSEMBL: ENSMUSP00000126930 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025791] [ENSMUST00000088737] [ENSMUST00000113837] [ENSMUST00000171123] [ENSMUST00000167511]
AlphaFold Q99MK8
Predicted Effect probably damaging
Transcript: ENSMUST00000025791
AA Change: I212F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: I212F

DomainStartEndE-ValueType
RGS 12 133 3.17e-30 SMART
S_TKc 149 411 2.43e-86 SMART
S_TK_X 412 491 5.3e-9 SMART
PH 517 612 2.79e-12 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000088737
AA Change: I254F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: I254F

DomainStartEndE-ValueType
RGS 54 175 3.17e-30 SMART
S_TKc 191 453 2.43e-86 SMART
S_TK_X 454 533 5.3e-9 SMART
PH 559 654 2.79e-12 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000113837
SMART Domains Protein: ENSMUSP00000109468
Gene: ENSMUSG00000024858

DomainStartEndE-ValueType
RGS 54 175 3.17e-30 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000164427
Predicted Effect probably benign
Transcript: ENSMUST00000165954
SMART Domains Protein: ENSMUSP00000128177
Gene: ENSMUSG00000024858

DomainStartEndE-ValueType
Pfam:Pkinase 1 169 5.8e-46 PFAM
Pfam:Pkinase_Tyr 2 155 9.3e-20 PFAM
S_TK_X 170 208 3.39e-1 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000167172
Predicted Effect probably damaging
Transcript: ENSMUST00000171123
AA Change: I254F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
AA Change: I254F

DomainStartEndE-ValueType
RGS 54 175 3.17e-30 SMART
Pfam:Pkinase_Tyr 191 378 1.1e-21 PFAM
Pfam:Pkinase 191 381 4.9e-50 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000169991
Predicted Effect probably benign
Transcript: ENSMUST00000168594
SMART Domains Protein: ENSMUSP00000126025
Gene: ENSMUSG00000024858

DomainStartEndE-ValueType
Blast:S_TKc 2 38 2e-18 BLAST
S_TK_X 39 85 2.95e-2 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000167511
SMART Domains Protein: ENSMUSP00000129839
Gene: ENSMUSG00000024858

DomainStartEndE-ValueType
Pfam:RGS 74 134 4.5e-10 PFAM
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.0%
  • 20x: 94.2%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The product of this gene phosphorylates the beta-2-adrenergic receptor and appears to mediate agonist-specific desensitization observed at high agonist concentrations. This protein is an ubiquitous cytosolic enzyme that specifically phosphorylates the activated form of the beta-adrenergic and related G-protein-coupled receptors. Abnormal coupling of beta-adrenergic receptor to G protein is involved in the pathogenesis of the failing heart. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutation of this gene results in embryonic lethality likely due to heart failure. Homozygous mutant embryos are pale in appearance and exhibit ventricular hypoplasia. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 64 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ablim1 A T 19: 57,035,450 (GRCm39) S316T probably damaging Het
Alox8 C T 11: 69,077,114 (GRCm39) V460I probably damaging Het
Aoc1l2 T C 6: 48,908,385 (GRCm39) S462P probably damaging Het
Arvcf G A 16: 18,218,482 (GRCm39) A491T probably damaging Het
Asnsd1 A G 1: 53,386,386 (GRCm39) S414P possibly damaging Het
Btbd7 A G 12: 102,756,968 (GRCm39) L706P probably damaging Het
Camk2d T A 3: 126,574,105 (GRCm39) W171R probably damaging Het
Casc3 T A 11: 98,712,332 (GRCm39) S124T probably benign Het
Casp8ap2 T C 4: 32,644,560 (GRCm39) V1211A probably benign Het
Ccdc182 T C 11: 88,184,962 (GRCm39) V14A possibly damaging Het
Ccdc80 A T 16: 44,943,275 (GRCm39) Q795L probably damaging Het
Ccdc88a T G 11: 29,453,480 (GRCm39) S1614R probably damaging Het
Cemip2 G A 19: 21,822,114 (GRCm39) A1170T possibly damaging Het
Clcn6 A G 4: 148,095,109 (GRCm39) probably null Het
Cubn A G 2: 13,313,360 (GRCm39) V3070A probably benign Het
Dst G A 1: 34,205,372 (GRCm39) V1025I possibly damaging Het
Dynlt4 A G 4: 116,985,504 (GRCm39) E109G possibly damaging Het
Elk3 T A 10: 93,101,539 (GRCm39) I71F probably damaging Het
Flt3 A T 5: 147,306,300 (GRCm39) I276N probably damaging Het
Frem1 G T 4: 82,831,795 (GRCm39) T1988K probably benign Het
Golph3l T A 3: 95,524,668 (GRCm39) D306E probably benign Het
Hgf C T 5: 16,781,919 (GRCm39) T214I probably benign Het
Hoxc5 C A 15: 102,922,814 (GRCm39) probably null Het
Hsd11b1 T C 1: 192,922,686 (GRCm39) T124A probably benign Het
Ipp A G 4: 116,372,565 (GRCm39) Y198C probably benign Het
Ism1 T A 2: 139,582,047 (GRCm39) probably null Het
Klhl42 A G 6: 146,993,394 (GRCm39) Y122C possibly damaging Het
Klk1b21 A T 7: 43,755,418 (GRCm39) K206* probably null Het
Lcn11 A G 2: 25,668,097 (GRCm39) K85R probably benign Het
Macf1 G T 4: 123,366,523 (GRCm39) A2746E probably damaging Het
Matn4 A G 2: 164,242,573 (GRCm39) V175A probably damaging Het
Myh2 A T 11: 67,082,545 (GRCm39) N1372Y probably damaging Het
Ncl A G 1: 86,284,677 (GRCm39) probably null Het
Nudt2 A G 4: 41,480,255 (GRCm39) D46G probably damaging Het
Obscn C T 11: 58,958,000 (GRCm39) D3567N probably benign Het
Or1j17 G C 2: 36,578,487 (GRCm39) V158L probably benign Het
Or2z9 G T 8: 72,853,930 (GRCm39) V109F possibly damaging Het
Or4a72 A T 2: 89,405,305 (GRCm39) M255K possibly damaging Het
Pamr1 T A 2: 102,464,880 (GRCm39) M343K probably benign Het
Pcdh15 T G 10: 74,467,025 (GRCm39) S1684A possibly damaging Het
Ppm1h T A 10: 122,714,433 (GRCm39) L324* probably null Het
Ppp3r2 T C 4: 49,681,723 (GRCm39) I76V probably benign Het
Prkdc G A 16: 15,494,873 (GRCm39) V748I probably benign Het
Prss47 A G 13: 65,199,591 (GRCm39) V96A probably benign Het
Rsbn1 C T 3: 103,821,789 (GRCm39) T8I probably benign Het
Rsf1 GGCG GGCGACGGCGGCG 7: 97,229,113 (GRCm39) probably benign Het
Serpinb3d A G 1: 107,006,182 (GRCm39) V302A probably benign Het
Sfrp4 A T 13: 19,816,496 (GRCm39) I177F probably benign Het
Sh3bp2 A G 5: 34,701,569 (GRCm39) probably benign Het
Slc7a12 A G 3: 14,562,393 (GRCm39) T257A probably damaging Het
Spata31e5 A T 1: 28,817,234 (GRCm39) V266D probably damaging Het
Specc1l T C 10: 75,103,425 (GRCm39) probably null Het
Stard9 A G 2: 120,534,716 (GRCm39) T3658A probably benign Het
Styxl2 A T 1: 165,928,392 (GRCm39) W407R probably benign Het
Tmem30c T C 16: 57,101,725 (GRCm39) T68A probably damaging Het
Tnr A G 1: 159,679,592 (GRCm39) I189V probably benign Het
Trrap A G 5: 144,790,298 (GRCm39) N3586S possibly damaging Het
Usp14 T C 18: 10,024,632 (GRCm39) T22A probably damaging Het
Vmn1r68 A G 7: 10,261,918 (GRCm39) L60P probably damaging Het
Vmn2r108 G A 17: 20,691,252 (GRCm39) H424Y probably benign Het
Wdr81 C A 11: 75,336,788 (GRCm39) E1534* probably null Het
Zc3h13 A G 14: 75,567,635 (GRCm39) E976G probably damaging Het
Zfp128 T C 7: 12,623,956 (GRCm39) L108P possibly damaging Het
Zfp644 T C 5: 106,783,548 (GRCm39) I1000V possibly damaging Het
Other mutations in Grk2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00757:Grk2 APN 19 4,339,339 (GRCm39) critical splice donor site probably null
IGL00927:Grk2 APN 19 4,337,982 (GRCm39) missense probably benign 0.09
IGL01465:Grk2 APN 19 4,340,886 (GRCm39) missense probably damaging 1.00
IGL02692:Grk2 APN 19 4,340,716 (GRCm39) splice site probably benign
IGL02870:Grk2 APN 19 4,340,430 (GRCm39) missense probably damaging 1.00
IGL03210:Grk2 APN 19 4,337,857 (GRCm39) missense probably benign 0.01
IGL03227:Grk2 APN 19 4,337,857 (GRCm39) missense probably benign 0.01
IGL03230:Grk2 APN 19 4,337,857 (GRCm39) missense probably benign 0.01
Greco UTSW 19 4,340,630 (GRCm39) critical splice donor site probably null
PIT4480001:Grk2 UTSW 19 4,337,437 (GRCm39) missense possibly damaging 0.93
R0008:Grk2 UTSW 19 4,337,262 (GRCm39) missense probably damaging 0.99
R0371:Grk2 UTSW 19 4,341,614 (GRCm39) splice site probably null
R0426:Grk2 UTSW 19 4,340,628 (GRCm39) splice site probably null
R0494:Grk2 UTSW 19 4,341,347 (GRCm39) missense probably damaging 1.00
R0833:Grk2 UTSW 19 4,339,385 (GRCm39) missense probably damaging 1.00
R1240:Grk2 UTSW 19 4,340,707 (GRCm39) missense probably damaging 1.00
R1446:Grk2 UTSW 19 4,337,437 (GRCm39) missense possibly damaging 0.93
R1499:Grk2 UTSW 19 4,337,222 (GRCm39) missense probably benign 0.11
R1664:Grk2 UTSW 19 4,337,268 (GRCm39) missense possibly damaging 0.48
R1796:Grk2 UTSW 19 4,337,968 (GRCm39) missense probably benign 0.12
R1803:Grk2 UTSW 19 4,344,911 (GRCm39) missense probably damaging 1.00
R3947:Grk2 UTSW 19 4,342,445 (GRCm39) missense possibly damaging 0.95
R4551:Grk2 UTSW 19 4,336,084 (GRCm39) missense possibly damaging 0.96
R4945:Grk2 UTSW 19 4,340,475 (GRCm39) missense probably damaging 1.00
R5299:Grk2 UTSW 19 4,342,799 (GRCm39) missense probably damaging 1.00
R5753:Grk2 UTSW 19 4,340,496 (GRCm39) missense probably damaging 1.00
R5754:Grk2 UTSW 19 4,340,496 (GRCm39) missense probably damaging 1.00
R5973:Grk2 UTSW 19 4,337,925 (GRCm39) missense possibly damaging 0.88
R6026:Grk2 UTSW 19 4,340,811 (GRCm39) missense probably damaging 0.99
R7117:Grk2 UTSW 19 4,340,630 (GRCm39) critical splice donor site probably null
R7468:Grk2 UTSW 19 4,356,063 (GRCm39) start gained probably benign
R7764:Grk2 UTSW 19 4,337,391 (GRCm39) missense probably damaging 1.00
R8250:Grk2 UTSW 19 4,339,962 (GRCm39) missense probably damaging 1.00
R8789:Grk2 UTSW 19 4,338,511 (GRCm39) missense probably damaging 1.00
R9468:Grk2 UTSW 19 4,344,952 (GRCm39) missense probably damaging 1.00
R9508:Grk2 UTSW 19 4,341,636 (GRCm39) missense probably damaging 1.00
R9526:Grk2 UTSW 19 4,340,871 (GRCm39) missense probably damaging 1.00
R9694:Grk2 UTSW 19 4,338,511 (GRCm39) missense probably damaging 1.00
X0009:Grk2 UTSW 19 4,341,617 (GRCm39) critical splice donor site probably null
Z1176:Grk2 UTSW 19 4,337,673 (GRCm39) missense probably benign 0.00
Predicted Primers PCR Primer
(F):5'- TGTCGGCTTCAGAGAAGACTC -3'
(R):5'- GTACGCCATGAAGTGTCTGGAC -3'

Sequencing Primer
(F):5'- GCTTCAGAGAAGACTCCATGCTG -3'
(R):5'- TGTCTGGACAAGAAACGCATC -3'
Posted On 2014-08-25