Incidental Mutation 'R4945:Grk2'
| ID |
381343 |
| 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 |
042542-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R4945 (G1)
|
| Quality Score |
224 |
|
Status
|
Not validated
|
| Chromosome |
19 |
| Chromosomal Location |
4336029-4356250 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 4340475 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Threonine
at position 302
(I302T)
|
| 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: I260T
PolyPhen 2
Score 0.884 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: I260T
| 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 |
possibly damaging
Transcript: ENSMUST00000088737
AA Change: I302T
PolyPhen 2
Score 0.803 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: I302T
| 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 |
possibly damaging
Transcript: ENSMUST00000165954
AA Change: I12T
PolyPhen 2
Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000128177
Gene: ENSMUSG00000024858
AA Change: I12T
| 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: I302T
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
AA Change: I302T
| 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 |
|
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.9%
- 20x: 94.3%
|
| 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: 70 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adamts13 |
G |
A |
2: 26,876,622 (GRCm39) |
R512H |
probably damaging |
Het |
| Adgrl2 |
T |
A |
3: 148,528,672 (GRCm39) |
M1158L |
probably damaging |
Het |
| Adgrl3 |
C |
A |
5: 81,659,895 (GRCm39) |
H153Q |
probably damaging |
Het |
| Aldh1a2 |
C |
A |
9: 71,123,198 (GRCm39) |
Q24K |
probably benign |
Het |
| Atp1b1 |
A |
G |
1: 164,265,867 (GRCm39) |
V298A |
probably damaging |
Het |
| Casp8ap2 |
T |
A |
4: 32,631,163 (GRCm39) |
N74K |
possibly damaging |
Het |
| Cep135 |
A |
G |
5: 76,745,275 (GRCm39) |
D229G |
probably benign |
Het |
| Cerk |
C |
G |
15: 86,040,802 (GRCm39) |
D186H |
probably benign |
Het |
| Cmtr2 |
T |
C |
8: 110,948,065 (GRCm39) |
F125S |
probably damaging |
Het |
| Col6a1 |
A |
G |
10: 76,548,106 (GRCm39) |
V650A |
unknown |
Het |
| Cuzd1 |
A |
G |
7: 130,918,350 (GRCm39) |
F196L |
probably damaging |
Het |
| Esm1 |
T |
G |
13: 113,346,679 (GRCm39) |
|
probably null |
Het |
| Fbn2 |
T |
A |
18: 58,183,325 (GRCm39) |
I1787F |
possibly damaging |
Het |
| Gm1110 |
T |
C |
9: 26,831,891 (GRCm39) |
M87V |
possibly damaging |
Het |
| Gpr179 |
T |
C |
11: 97,240,544 (GRCm39) |
H293R |
probably damaging |
Het |
| Hoxb6 |
A |
G |
11: 96,190,085 (GRCm39) |
Y28C |
possibly damaging |
Het |
| Ift27 |
A |
G |
15: 78,048,454 (GRCm39) |
V110A |
probably damaging |
Het |
| Igfbp7 |
T |
C |
5: 77,499,104 (GRCm39) |
D267G |
probably benign |
Het |
| Ighv1-49 |
C |
A |
12: 115,019,028 (GRCm39) |
V56L |
possibly damaging |
Het |
| Ighv8-8 |
C |
T |
12: 115,257,881 (GRCm39) |
M53I |
probably benign |
Het |
| Kcnj3 |
T |
A |
2: 55,327,590 (GRCm39) |
N126K |
probably damaging |
Het |
| Kif12 |
C |
T |
4: 63,086,730 (GRCm39) |
|
probably null |
Het |
| Lrif1 |
A |
C |
3: 106,643,069 (GRCm39) |
I725L |
probably damaging |
Het |
| Lrrk2 |
T |
C |
15: 91,689,123 (GRCm39) |
V2265A |
probably benign |
Het |
| Med25 |
T |
C |
7: 44,532,526 (GRCm39) |
N438S |
possibly damaging |
Het |
| Mex3b |
A |
T |
7: 82,519,382 (GRCm39) |
T566S |
probably benign |
Het |
| Mkx |
T |
C |
18: 7,000,657 (GRCm39) |
N95S |
possibly damaging |
Het |
| Morc3 |
A |
T |
16: 93,668,082 (GRCm39) |
D820V |
probably damaging |
Het |
| Mroh4 |
G |
T |
15: 74,483,857 (GRCm39) |
N562K |
probably benign |
Het |
| Ndst3 |
A |
T |
3: 123,346,201 (GRCm39) |
I276N |
probably damaging |
Het |
| Notch2 |
A |
G |
3: 98,019,037 (GRCm39) |
N733S |
probably benign |
Het |
| Or10a5 |
A |
T |
7: 106,635,526 (GRCm39) |
M55L |
probably benign |
Het |
| Or2l13b |
C |
A |
16: 19,349,307 (GRCm39) |
R121L |
probably benign |
Het |
| Or51k1 |
G |
A |
7: 103,661,585 (GRCm39) |
T108I |
possibly damaging |
Het |
| Or5ak24 |
T |
C |
2: 85,260,895 (GRCm39) |
T93A |
probably benign |
Het |
| Or5m13 |
T |
A |
2: 85,748,917 (GRCm39) |
I216N |
possibly damaging |
Het |
| Or8b38 |
G |
T |
9: 37,973,068 (GRCm39) |
G151C |
probably damaging |
Het |
| Or8b44 |
A |
T |
9: 38,410,585 (GRCm39) |
I207F |
probably damaging |
Het |
| Or8k37 |
T |
C |
2: 86,469,833 (GRCm39) |
Y73C |
probably damaging |
Het |
| Patj |
A |
T |
4: 98,383,301 (GRCm39) |
N268Y |
probably damaging |
Het |
| Pbrm1 |
T |
A |
14: 30,774,173 (GRCm39) |
D446E |
probably damaging |
Het |
| Pcdhga11 |
A |
G |
18: 37,891,085 (GRCm39) |
T698A |
probably benign |
Het |
| Pde6a |
T |
C |
18: 61,367,790 (GRCm39) |
V266A |
probably damaging |
Het |
| Phax |
G |
T |
18: 56,709,063 (GRCm39) |
R209L |
probably damaging |
Het |
| Pld2 |
T |
A |
11: 70,446,524 (GRCm39) |
M20K |
probably damaging |
Het |
| Rabl3 |
T |
C |
16: 37,362,220 (GRCm39) |
S20P |
probably damaging |
Het |
| Rad51 |
T |
A |
2: 118,957,629 (GRCm39) |
V174E |
probably damaging |
Het |
| Rb1cc1 |
A |
G |
1: 6,319,851 (GRCm39) |
E1090G |
probably benign |
Het |
| Rfc3 |
T |
C |
5: 151,566,450 (GRCm39) |
E333G |
probably damaging |
Het |
| Rfx6 |
T |
G |
10: 51,602,947 (GRCm39) |
Y821* |
probably null |
Het |
| Riok3 |
A |
G |
18: 12,261,972 (GRCm39) |
D2G |
probably damaging |
Het |
| Rtn1 |
G |
T |
12: 72,264,258 (GRCm39) |
A183E |
probably damaging |
Het |
| Skint8 |
T |
C |
4: 111,796,805 (GRCm39) |
L303P |
probably damaging |
Het |
| Slc36a2 |
C |
A |
11: 55,065,520 (GRCm39) |
V162L |
probably benign |
Het |
| Sorcs3 |
T |
C |
19: 48,752,587 (GRCm39) |
V794A |
possibly damaging |
Het |
| Sspo |
A |
G |
6: 48,444,021 (GRCm39) |
|
probably null |
Het |
| Tbk1 |
T |
C |
10: 121,387,174 (GRCm39) |
N707S |
probably damaging |
Het |
| Tchhl1 |
A |
T |
3: 93,378,883 (GRCm39) |
H529L |
probably benign |
Het |
| Tgfbr2 |
A |
T |
9: 115,960,633 (GRCm39) |
H106Q |
probably benign |
Het |
| Trim8 |
A |
G |
19: 46,491,214 (GRCm39) |
E111G |
probably benign |
Het |
| Tshz2 |
A |
G |
2: 169,725,794 (GRCm39) |
Y130C |
probably damaging |
Het |
| Txndc15 |
T |
A |
13: 55,865,978 (GRCm39) |
D147E |
probably benign |
Het |
| Vmn1r172 |
T |
A |
7: 23,359,745 (GRCm39) |
L210H |
possibly damaging |
Het |
| Vmn1r55 |
A |
G |
7: 5,150,105 (GRCm39) |
V106A |
probably damaging |
Het |
| Vmn2r49 |
T |
A |
7: 9,720,214 (GRCm39) |
K426* |
probably null |
Het |
| Wnk2 |
C |
T |
13: 49,210,722 (GRCm39) |
R206Q |
probably damaging |
Het |
| Zfp1007 |
A |
T |
5: 109,824,941 (GRCm39) |
C170S |
possibly damaging |
Het |
| Zfp473 |
T |
C |
7: 44,383,988 (GRCm39) |
N115S |
probably benign |
Het |
| Zfp536 |
G |
T |
7: 37,269,161 (GRCm39) |
A85D |
probably damaging |
Het |
| Zfp853 |
C |
A |
5: 143,274,584 (GRCm39) |
Q345H |
unknown |
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 |
|
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'- AGGGAACTACATGGTTTTGGGAC -3'
(R):5'- TCATCCTGGACCTCATGAACG -3'
Sequencing Primer
(F):5'- ACAAGGCCCCAGGTAGG -3'
(R):5'- ACCTCATGAACGGTGAGCTC -3'
|
| Posted On |
2016-04-27 |
Incidental Mutation