Incidental Mutation 'R1664:Grk2'
| ID |
187072 |
| 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 |
039700-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1664 (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 C
at 4337268 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Lysine to Glutamic Acid
at position 644
(K644E)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000086114
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025791]
[ENSMUST00000056888]
[ENSMUST00000088737]
[ENSMUST00000113837]
[ENSMUST00000163858]
[ENSMUST00000171123]
[ENSMUST00000167215]
|
| AlphaFold |
Q99MK8 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000025791
AA Change: K602E
PolyPhen 2
Score 0.483 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: K602E
| 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 benign
Transcript: ENSMUST00000056888
|
| SMART Domains |
Protein: ENSMUSP00000053783
Gene: ENSMUSG00000005986
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
39 |
68 |
2.77e-3 |
SMART |
|
ANK
|
72 |
101 |
9.75e1 |
SMART |
|
Pfam:GPCR_chapero_1
|
155 |
469 |
1.2e-111 |
PFAM |
|
UIM
|
482 |
501 |
3.2e-2 |
SMART |
|
UIM
|
528 |
547 |
1.92e2 |
SMART |
|
UIM
|
564 |
583 |
8.18e0 |
SMART |
|
UIM
|
589 |
605 |
6e2 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000088737
AA Change: K644E
PolyPhen 2
Score 0.483 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: K644E
| 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 |
probably benign
Transcript: ENSMUST00000163858
|
| SMART Domains |
Protein: ENSMUSP00000128932
Gene: ENSMUSG00000005986
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
39 |
68 |
2.77e-3 |
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: ENSMUST00000169991
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000167172
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000169653
|
| 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 |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000171123
|
| SMART Domains |
Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
| 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 |
probably benign
Transcript: ENSMUST00000167215
|
| SMART Domains |
Protein: ENSMUSP00000128037
Gene: ENSMUSG00000005986
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
39 |
68 |
2.77e-3 |
SMART |
|
ANK
|
72 |
101 |
9.75e1 |
SMART |
|
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.4%
- 10x: 96.5%
- 20x: 93.0%
|
| 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: 81 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930596D02Rik |
T |
A |
14: 35,533,772 (GRCm39) |
T45S |
probably benign |
Het |
| Ackr1 |
A |
G |
1: 173,160,433 (GRCm39) |
F29L |
probably benign |
Het |
| Adgrf2 |
T |
A |
17: 43,025,305 (GRCm39) |
S60C |
possibly damaging |
Het |
| Alpk2 |
A |
G |
18: 65,482,944 (GRCm39) |
C355R |
probably damaging |
Het |
| Ankmy1 |
A |
C |
1: 92,812,913 (GRCm39) |
D465E |
probably benign |
Het |
| Ankrd27 |
T |
A |
7: 35,306,551 (GRCm39) |
D310E |
probably damaging |
Het |
| Ap3d1 |
G |
A |
10: 80,553,571 (GRCm39) |
Q559* |
probably null |
Het |
| C4b |
T |
C |
17: 34,951,952 (GRCm39) |
T1298A |
probably damaging |
Het |
| Casr |
T |
A |
16: 36,330,327 (GRCm39) |
K336* |
probably null |
Het |
| Ccdc116 |
A |
T |
16: 16,960,492 (GRCm39) |
D108E |
probably benign |
Het |
| Ccdc168 |
T |
A |
1: 44,098,387 (GRCm39) |
I904F |
possibly damaging |
Het |
| Ccr7 |
A |
T |
11: 99,036,517 (GRCm39) |
I135N |
possibly damaging |
Het |
| Cd96 |
A |
G |
16: 45,938,364 (GRCm39) |
Y34H |
possibly damaging |
Het |
| Cdan1 |
T |
A |
2: 120,550,987 (GRCm39) |
D1135V |
probably damaging |
Het |
| Cecr2 |
C |
A |
6: 120,738,987 (GRCm39) |
T1210K |
probably damaging |
Het |
| Cep152 |
C |
A |
2: 125,408,174 (GRCm39) |
A1390S |
probably benign |
Het |
| Chd9 |
T |
G |
8: 91,749,418 (GRCm39) |
|
probably null |
Het |
| Cntnap5c |
G |
T |
17: 58,600,985 (GRCm39) |
W776L |
probably benign |
Het |
| Col24a1 |
G |
A |
3: 145,095,355 (GRCm39) |
|
probably null |
Het |
| Cpa2 |
G |
T |
6: 30,554,314 (GRCm39) |
M311I |
probably damaging |
Het |
| Cpz |
A |
G |
5: 35,664,087 (GRCm39) |
F483L |
probably damaging |
Het |
| Ddx19a |
A |
C |
8: 111,716,130 (GRCm39) |
V90G |
probably damaging |
Het |
| Fabp3 |
C |
T |
4: 130,206,180 (GRCm39) |
T57I |
probably benign |
Het |
| Fbxw7 |
A |
G |
3: 84,876,478 (GRCm39) |
D213G |
possibly damaging |
Het |
| Fgd2 |
T |
C |
17: 29,588,273 (GRCm39) |
F362L |
probably damaging |
Het |
| Fryl |
A |
G |
5: 73,216,778 (GRCm39) |
Y2171H |
probably damaging |
Het |
| Gba2 |
T |
C |
4: 43,578,080 (GRCm39) |
R90G |
probably benign |
Het |
| Gm10073 |
T |
C |
8: 107,299,864 (GRCm39) |
E40G |
probably damaging |
Het |
| Grhl3 |
T |
C |
4: 135,279,861 (GRCm39) |
I398V |
probably benign |
Het |
| Grip2 |
T |
A |
6: 91,742,233 (GRCm39) |
H899L |
probably damaging |
Het |
| Iars1 |
A |
T |
13: 49,865,251 (GRCm39) |
T576S |
probably damaging |
Het |
| Kif26b |
G |
A |
1: 178,759,704 (GRCm39) |
V2084M |
probably damaging |
Het |
| Kirrel1 |
C |
T |
3: 86,996,458 (GRCm39) |
M380I |
probably null |
Het |
| Lrrc69 |
G |
A |
4: 14,775,079 (GRCm39) |
T63M |
probably damaging |
Het |
| Lrrn4 |
A |
T |
2: 132,711,886 (GRCm39) |
C646S |
probably damaging |
Het |
| Mtf2 |
C |
T |
5: 108,252,342 (GRCm39) |
T457M |
probably damaging |
Het |
| Ncln |
A |
T |
10: 81,323,555 (GRCm39) |
C531S |
probably benign |
Het |
| Ntn4 |
C |
T |
10: 93,543,215 (GRCm39) |
R314W |
probably damaging |
Het |
| Or14j8 |
T |
C |
17: 38,263,784 (GRCm39) |
I44V |
probably benign |
Het |
| Or5v1 |
C |
T |
17: 37,810,316 (GRCm39) |
T258M |
possibly damaging |
Het |
| Or8c11 |
A |
T |
9: 38,289,548 (GRCm39) |
M124L |
possibly damaging |
Het |
| Otogl |
A |
G |
10: 107,642,437 (GRCm39) |
V1331A |
probably benign |
Het |
| Palb2 |
A |
G |
7: 121,723,615 (GRCm39) |
|
probably benign |
Het |
| Pcdh20 |
T |
C |
14: 88,705,758 (GRCm39) |
E514G |
possibly damaging |
Het |
| Pclaf |
A |
G |
9: 65,797,730 (GRCm39) |
N7S |
probably benign |
Het |
| Pdrg1 |
C |
T |
2: 152,857,248 (GRCm39) |
|
probably benign |
Het |
| Phf8-ps |
T |
A |
17: 33,285,492 (GRCm39) |
I437F |
probably damaging |
Het |
| Pik3r6 |
T |
A |
11: 68,426,932 (GRCm39) |
D464E |
probably benign |
Het |
| Pkp3 |
A |
G |
7: 140,667,560 (GRCm39) |
N454D |
probably damaging |
Het |
| Plekha7 |
C |
A |
7: 115,734,269 (GRCm39) |
|
probably null |
Het |
| Ppip5k1 |
A |
G |
2: 121,167,663 (GRCm39) |
V784A |
probably benign |
Het |
| Ppp1r36 |
T |
A |
12: 76,483,028 (GRCm39) |
D205E |
possibly damaging |
Het |
| Prss35 |
A |
T |
9: 86,637,700 (GRCm39) |
T157S |
probably benign |
Het |
| Ptprn2 |
T |
C |
12: 117,125,329 (GRCm39) |
L621P |
probably damaging |
Het |
| Rasgrp3 |
A |
G |
17: 75,831,172 (GRCm39) |
K524R |
probably damaging |
Het |
| Rasgrp4 |
T |
A |
7: 28,839,688 (GRCm39) |
H133Q |
probably benign |
Het |
| Reln |
A |
T |
5: 22,134,084 (GRCm39) |
Y2615N |
probably damaging |
Het |
| Rpf1 |
T |
A |
3: 146,217,903 (GRCm39) |
T204S |
probably benign |
Het |
| Scgb2b3 |
T |
A |
7: 31,058,464 (GRCm39) |
*113L |
probably null |
Het |
| Scn5a |
A |
C |
9: 119,350,243 (GRCm39) |
L877R |
possibly damaging |
Het |
| Sh3pxd2a |
A |
T |
19: 47,256,821 (GRCm39) |
D632E |
probably benign |
Het |
| Slc39a10 |
T |
C |
1: 46,865,269 (GRCm39) |
H522R |
probably damaging |
Het |
| Spink2 |
A |
T |
5: 77,354,855 (GRCm39) |
C19S |
probably damaging |
Het |
| Spsb4 |
A |
G |
9: 96,878,266 (GRCm39) |
L19P |
possibly damaging |
Het |
| St7l |
T |
C |
3: 104,778,214 (GRCm39) |
V117A |
probably damaging |
Het |
| Stac2 |
C |
T |
11: 97,933,420 (GRCm39) |
S174N |
probably damaging |
Het |
| Sult4a1 |
A |
G |
15: 83,970,818 (GRCm39) |
Y196H |
probably benign |
Het |
| Tex2 |
C |
T |
11: 106,458,608 (GRCm39) |
|
probably benign |
Het |
| Tprg1l |
A |
T |
4: 154,243,862 (GRCm39) |
V98D |
possibly damaging |
Het |
| Ttn |
G |
A |
2: 76,548,369 (GRCm39) |
H31978Y |
probably damaging |
Het |
| Ttn |
T |
C |
2: 76,658,853 (GRCm39) |
|
probably benign |
Het |
| Tyk2 |
C |
A |
9: 21,031,649 (GRCm39) |
R447L |
probably damaging |
Het |
| Ucn3 |
T |
C |
13: 3,991,634 (GRCm39) |
Y6C |
possibly damaging |
Het |
| Urb1 |
A |
T |
16: 90,584,970 (GRCm39) |
|
probably null |
Het |
| Vmn2r94 |
G |
C |
17: 18,464,406 (GRCm39) |
A628G |
probably damaging |
Het |
| Wdr95 |
C |
A |
5: 149,518,752 (GRCm39) |
T389K |
probably damaging |
Het |
| Wrn |
A |
T |
8: 33,770,794 (GRCm39) |
|
probably null |
Het |
| Xab2 |
T |
A |
8: 3,669,068 (GRCm39) |
|
probably null |
Het |
| Zfp458 |
A |
T |
13: 67,406,144 (GRCm39) |
N95K |
possibly damaging |
Het |
| Zfp672 |
T |
C |
11: 58,208,138 (GRCm39) |
H61R |
probably damaging |
Het |
| Zfp942 |
C |
T |
17: 22,147,420 (GRCm39) |
G403E |
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 |
|
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 |
|
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'- TCAAGTAGTACCCTGTGTTGCCCC -3'
(R):5'- CGCAAGTGTCTCCTGCTTAAGATCC -3'
Sequencing Primer
(F):5'- TCCGCTTTGCGGGAAAAC -3'
(R):5'- CTCCTGCTTAAGATCCGAGGTG -3'
|
| Posted On |
2014-05-09 |
Incidental Mutation