Incidental Mutation 'R6026:Grk2'
| ID |
480082 |
| 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 |
044198-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6026 (G1)
|
| Quality Score |
215.009 |
|
Status
|
Validated
|
| Chromosome |
19 |
| Chromosomal Location |
4336029-4356250 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 4340811 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Isoleucine
at position 246
(V246I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000126930
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025791]
[ENSMUST00000088737]
[ENSMUST00000113837]
[ENSMUST00000167511]
[ENSMUST00000171123]
|
| AlphaFold |
Q99MK8 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000025791
AA Change: V204I
PolyPhen 2
Score 0.940 (Sensitivity: 0.80; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: V204I
| Domain | Start | End | E-Value | Type |
|---|
|
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: V246I
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: V246I
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000167511
|
| SMART Domains |
Protein: ENSMUSP00000129839
Gene: ENSMUSG00000024858
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:RGS
|
74 |
134 |
4.5e-10 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000171123
AA Change: V246I
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
AA Change: V246I
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:S_TKc
|
2 |
38 |
2e-18 |
BLAST |
|
S_TK_X
|
39 |
85 |
2.95e-2 |
SMART |
|
| Meta Mutation Damage Score |
0.2367 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 97.9%
- 20x: 93.5%
|
| Validation Efficiency |
97% (73/75) |
| 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: 74 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1810065E05Rik |
A |
G |
11: 58,316,581 (GRCm39) |
D187G |
probably benign |
Het |
| 4933421I07Rik |
A |
T |
7: 42,095,708 (GRCm39) |
M180K |
probably benign |
Het |
| Aatk |
T |
C |
11: 119,903,190 (GRCm39) |
H345R |
possibly damaging |
Het |
| Abcc8 |
T |
C |
7: 45,816,424 (GRCm39) |
T239A |
probably benign |
Het |
| Abcf3 |
A |
G |
16: 20,369,320 (GRCm39) |
E234G |
probably damaging |
Het |
| Actrt2 |
T |
C |
4: 154,751,047 (GRCm39) |
D363G |
possibly damaging |
Het |
| Adam1a |
A |
T |
5: 121,657,425 (GRCm39) |
C623S |
probably damaging |
Het |
| Afg3l2 |
G |
T |
18: 67,554,329 (GRCm39) |
L458M |
probably damaging |
Het |
| Ash1l |
T |
C |
3: 88,892,326 (GRCm39) |
Y1402H |
probably damaging |
Het |
| Barhl2 |
T |
A |
5: 106,603,474 (GRCm39) |
K228N |
probably benign |
Het |
| Blvrb |
A |
G |
7: 27,162,115 (GRCm39) |
H153R |
probably damaging |
Het |
| Capn9 |
A |
G |
8: 125,332,601 (GRCm39) |
D480G |
probably damaging |
Het |
| Cct3 |
T |
C |
3: 88,219,029 (GRCm39) |
I182T |
possibly damaging |
Het |
| Clasp2 |
A |
G |
9: 113,740,646 (GRCm39) |
N1208D |
probably benign |
Het |
| Col26a1 |
A |
G |
5: 136,876,354 (GRCm39) |
C89R |
probably damaging |
Het |
| Cops4 |
T |
A |
5: 100,690,194 (GRCm39) |
|
probably benign |
Het |
| Cpox |
T |
A |
16: 58,491,298 (GRCm39) |
W170R |
probably damaging |
Het |
| Ddx27 |
A |
G |
2: 166,875,560 (GRCm39) |
K656E |
probably benign |
Het |
| Eif4e |
T |
C |
3: 138,256,661 (GRCm39) |
I66T |
probably damaging |
Het |
| Ercc3 |
T |
C |
18: 32,378,974 (GRCm39) |
|
probably null |
Het |
| Esp38 |
G |
A |
17: 40,266,032 (GRCm39) |
C47Y |
probably damaging |
Het |
| Fancd2 |
T |
C |
6: 113,528,731 (GRCm39) |
V380A |
possibly damaging |
Het |
| Fbxw7 |
T |
A |
3: 84,859,948 (GRCm39) |
|
probably null |
Het |
| Fryl |
T |
G |
5: 73,257,340 (GRCm39) |
R736S |
probably benign |
Het |
| Gad2 |
G |
A |
2: 22,513,748 (GRCm39) |
V62M |
probably benign |
Het |
| Gigyf2 |
A |
G |
1: 87,368,454 (GRCm39) |
T1045A |
probably damaging |
Het |
| Gm13090 |
T |
A |
4: 151,175,157 (GRCm39) |
L78* |
probably null |
Het |
| Gm19410 |
G |
A |
8: 36,279,580 (GRCm39) |
S1815N |
probably benign |
Het |
| Gm28051 |
A |
T |
12: 102,686,444 (GRCm39) |
L72Q |
unknown |
Het |
| Gm44511 |
T |
C |
6: 128,797,240 (GRCm39) |
T83A |
possibly damaging |
Het |
| Grm7 |
C |
T |
6: 111,478,500 (GRCm39) |
Q62* |
probably null |
Het |
| Gsdmc3 |
T |
A |
15: 63,738,600 (GRCm39) |
E154V |
probably damaging |
Het |
| Gstz1 |
A |
C |
12: 87,206,948 (GRCm39) |
Q114P |
probably damaging |
Het |
| Hax1 |
GTCATCATCATCATCATC |
GTCATCATCATCATCATCATC |
3: 89,905,247 (GRCm39) |
|
probably benign |
Het |
| Hhip |
A |
T |
8: 80,699,069 (GRCm39) |
C666S |
probably damaging |
Het |
| Hif1a |
A |
C |
12: 73,979,055 (GRCm39) |
H193P |
probably damaging |
Het |
| Hyal2 |
A |
G |
9: 107,449,398 (GRCm39) |
T385A |
probably benign |
Het |
| Ihh |
T |
C |
1: 74,985,886 (GRCm39) |
T200A |
probably benign |
Het |
| Iqgap3 |
T |
A |
3: 87,997,478 (GRCm39) |
V218E |
probably damaging |
Het |
| Lct |
A |
G |
1: 128,227,755 (GRCm39) |
I1246T |
probably benign |
Het |
| Lmo7 |
T |
C |
14: 102,118,426 (GRCm39) |
V217A |
probably benign |
Het |
| Lrp1 |
C |
T |
10: 127,409,272 (GRCm39) |
D1616N |
probably damaging |
Het |
| Lrrfip2 |
A |
T |
9: 111,043,239 (GRCm39) |
T165S |
probably damaging |
Het |
| Morc2b |
A |
G |
17: 33,356,957 (GRCm39) |
Y272H |
possibly damaging |
Het |
| Muc16 |
A |
G |
9: 18,571,154 (GRCm39) |
M455T |
unknown |
Het |
| Ncapg2 |
A |
T |
12: 116,406,641 (GRCm39) |
D939V |
possibly damaging |
Het |
| Ncbp3 |
T |
C |
11: 72,958,548 (GRCm39) |
V236A |
probably benign |
Het |
| Obscn |
T |
A |
11: 58,957,916 (GRCm39) |
T3595S |
probably damaging |
Het |
| Odf2l |
T |
C |
3: 144,854,797 (GRCm39) |
S545P |
possibly damaging |
Het |
| Or3a1 |
T |
A |
11: 74,225,914 (GRCm39) |
I48F |
probably damaging |
Het |
| Or8b36 |
ATTGCTGTTT |
ATTGCTGTTTGCTGTTT |
9: 37,937,836 (GRCm39) |
|
probably null |
Het |
| Pdzrn3 |
A |
C |
6: 101,339,105 (GRCm39) |
C269G |
probably benign |
Het |
| Pear1 |
T |
A |
3: 87,664,220 (GRCm39) |
N278Y |
probably damaging |
Het |
| Phb1 |
C |
T |
11: 95,562,245 (GRCm39) |
R41* |
probably null |
Het |
| Pikfyve |
T |
C |
1: 65,311,856 (GRCm39) |
V2031A |
probably damaging |
Het |
| Plxna2 |
A |
G |
1: 194,482,122 (GRCm39) |
I1465V |
probably damaging |
Het |
| Ppp6r2 |
A |
G |
15: 89,167,113 (GRCm39) |
N776S |
probably benign |
Het |
| Prkce |
A |
T |
17: 86,800,658 (GRCm39) |
E358V |
probably benign |
Het |
| Prl5a1 |
A |
T |
13: 28,335,247 (GRCm39) |
I219F |
probably benign |
Het |
| Prss3 |
T |
C |
6: 41,354,488 (GRCm39) |
|
probably null |
Het |
| Ptprc |
A |
T |
1: 137,998,987 (GRCm39) |
M858K |
probably damaging |
Het |
| Retreg3 |
T |
C |
11: 100,997,226 (GRCm39) |
T85A |
probably damaging |
Het |
| Rfc2 |
T |
A |
5: 134,624,185 (GRCm39) |
C265S |
probably damaging |
Het |
| Smarcd1 |
G |
T |
15: 99,603,619 (GRCm39) |
V256L |
probably damaging |
Het |
| Stat5a |
T |
C |
11: 100,771,142 (GRCm39) |
F574L |
probably damaging |
Het |
| Tcirg1 |
T |
C |
19: 3,947,487 (GRCm39) |
H624R |
probably benign |
Het |
| Tcstv1a |
C |
A |
13: 120,355,987 (GRCm39) |
|
probably benign |
Het |
| Tenm2 |
C |
T |
11: 35,963,556 (GRCm39) |
|
probably null |
Het |
| Tomm40 |
A |
G |
7: 19,444,889 (GRCm39) |
V164A |
probably benign |
Het |
| Txnl4a |
T |
C |
18: 80,250,482 (GRCm39) |
V26A |
probably damaging |
Het |
| Ugt2a3 |
A |
T |
5: 87,484,336 (GRCm39) |
F229L |
probably benign |
Het |
| Utp20 |
T |
C |
10: 88,604,541 (GRCm39) |
T1785A |
probably benign |
Het |
| Vmn1r22 |
T |
A |
6: 57,877,390 (GRCm39) |
I196L |
probably benign |
Het |
| Zfp652 |
T |
G |
11: 95,640,788 (GRCm39) |
C238G |
possibly damaging |
Het |
|
| Other mutations in Grk2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
R2021:Grk2
|
UTSW |
19 |
4,340,698 (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 |
|
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'- GTTCATGAGGTCCAGGATGAAGC -3'
(R):5'- TCCTGCGCTCTCTAAAGCAC -3'
Sequencing Primer
(F):5'- GTCCAGGATGAAGCTGAGC -3'
(R):5'- GCGCTCTCTAAAGCACTGGTTG -3'
|
| Posted On |
2017-06-26 |
Incidental Mutation