Incidental Mutation 'R1446:Grk2'
| ID |
158913 |
| 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 |
039501-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1446 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
19 |
| Chromosomal Location |
4336029-4356250 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 4337437 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Cysteine
at position 617
(R617C)
|
| 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: R575C
PolyPhen 2
Score 0.928 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: R575C
| 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: R617C
PolyPhen 2
Score 0.928 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: R617C
| 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: ENSMUST00000167172
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000169991
|
| 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: 99.0%
- 3x: 98.0%
- 10x: 95.3%
- 20x: 89.6%
|
| 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: 72 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aasdh |
C |
T |
5: 77,034,136 (GRCm39) |
A472T |
probably benign |
Het |
| Adcy4 |
A |
T |
14: 56,007,480 (GRCm39) |
|
probably null |
Het |
| Ahcyl2 |
T |
C |
6: 29,891,239 (GRCm39) |
S448P |
probably damaging |
Het |
| Anks1b |
A |
G |
10: 90,346,935 (GRCm39) |
Y745C |
probably benign |
Het |
| Anxa1 |
A |
T |
19: 20,351,103 (GRCm39) |
L339Q |
probably damaging |
Het |
| Apoa4 |
A |
G |
9: 46,153,591 (GRCm39) |
D64G |
probably benign |
Het |
| Arpc1a |
A |
G |
5: 145,037,896 (GRCm39) |
|
probably null |
Het |
| Bank1 |
C |
T |
3: 135,769,904 (GRCm39) |
G727R |
probably damaging |
Het |
| Best2 |
T |
C |
8: 85,734,593 (GRCm39) |
Q375R |
probably benign |
Het |
| Cacna1b |
T |
A |
2: 24,596,189 (GRCm39) |
M501L |
probably benign |
Het |
| Col27a1 |
T |
A |
4: 63,143,040 (GRCm39) |
Y243N |
probably damaging |
Het |
| Cyp11a1 |
A |
T |
9: 57,922,560 (GRCm39) |
Q80L |
possibly damaging |
Het |
| Dnah10 |
T |
A |
5: 124,866,860 (GRCm39) |
W2260R |
probably damaging |
Het |
| Dnajc19 |
T |
C |
3: 34,112,128 (GRCm39) |
H139R |
probably benign |
Het |
| Dppa5a |
T |
A |
9: 78,275,071 (GRCm39) |
N77I |
probably benign |
Het |
| Edc4 |
T |
C |
8: 106,614,764 (GRCm39) |
S125P |
probably damaging |
Het |
| Eid2 |
T |
C |
7: 27,968,014 (GRCm39) |
I212T |
possibly damaging |
Het |
| Fam234b |
T |
A |
6: 135,186,328 (GRCm39) |
|
probably null |
Het |
| Frem2 |
T |
C |
3: 53,562,017 (GRCm39) |
E830G |
probably benign |
Het |
| Fyb1 |
A |
T |
15: 6,681,947 (GRCm39) |
I765L |
probably benign |
Het |
| Fyn |
T |
G |
10: 39,398,775 (GRCm39) |
S124A |
probably benign |
Het |
| Gal3st3 |
T |
A |
19: 5,356,939 (GRCm39) |
F105I |
probably damaging |
Het |
| Gpr146 |
A |
G |
5: 139,379,177 (GRCm39) |
I326M |
probably benign |
Het |
| Gsn |
A |
G |
2: 35,196,598 (GRCm39) |
K669R |
probably benign |
Het |
| H2-T10 |
A |
T |
17: 36,430,266 (GRCm39) |
I225N |
possibly damaging |
Het |
| Il12rb2 |
T |
C |
6: 67,286,127 (GRCm39) |
H106R |
probably benign |
Het |
| Kat14 |
A |
G |
2: 144,215,638 (GRCm39) |
E41G |
probably damaging |
Het |
| Kcnma1 |
G |
T |
14: 23,361,792 (GRCm39) |
T1006K |
probably damaging |
Het |
| Kif18b |
G |
A |
11: 102,805,525 (GRCm39) |
T244I |
probably damaging |
Het |
| Klb |
A |
T |
5: 65,506,338 (GRCm39) |
H195L |
probably damaging |
Het |
| Lrriq4 |
T |
C |
3: 30,704,727 (GRCm39) |
F252L |
probably benign |
Het |
| Lum |
C |
T |
10: 97,404,252 (GRCm39) |
T49I |
possibly damaging |
Het |
| Map3k4 |
T |
A |
17: 12,475,681 (GRCm39) |
L84* |
probably null |
Het |
| Mindy2 |
A |
G |
9: 70,514,738 (GRCm39) |
|
probably null |
Het |
| Mpped2 |
G |
T |
2: 106,614,077 (GRCm39) |
R137L |
possibly damaging |
Het |
| Myo18b |
G |
A |
5: 112,905,425 (GRCm39) |
R2058W |
probably damaging |
Het |
| Nol8 |
T |
A |
13: 49,808,703 (GRCm39) |
L65Q |
probably damaging |
Het |
| Or11g27 |
T |
C |
14: 50,771,159 (GRCm39) |
S97P |
possibly damaging |
Het |
| Or4c108 |
A |
G |
2: 88,804,109 (GRCm39) |
I42T |
probably benign |
Het |
| Or4x6 |
A |
T |
2: 89,949,202 (GRCm39) |
L247M |
probably damaging |
Het |
| Or5b105 |
G |
A |
19: 13,080,380 (GRCm39) |
A96V |
possibly damaging |
Het |
| Or5g9 |
A |
G |
2: 85,551,917 (GRCm39) |
H56R |
probably damaging |
Het |
| Or8b3 |
T |
G |
9: 38,314,601 (GRCm39) |
C144G |
possibly damaging |
Het |
| Or9a4 |
C |
T |
6: 40,548,833 (GRCm39) |
S171L |
probably benign |
Het |
| Parp12 |
G |
T |
6: 39,079,495 (GRCm39) |
D338E |
probably benign |
Het |
| Pde6d |
T |
C |
1: 86,474,414 (GRCm39) |
E77G |
probably damaging |
Het |
| Phkg1 |
A |
C |
5: 129,902,055 (GRCm39) |
|
probably null |
Het |
| Pigw |
A |
C |
11: 84,769,186 (GRCm39) |
S48A |
probably benign |
Het |
| Pkm |
T |
A |
9: 59,576,193 (GRCm39) |
|
probably null |
Het |
| Ppp1r3f |
G |
A |
X: 7,426,602 (GRCm39) |
T553M |
probably damaging |
Het |
| Retreg2 |
T |
A |
1: 75,120,103 (GRCm39) |
F44L |
possibly damaging |
Het |
| Ryr2 |
A |
T |
13: 11,753,035 (GRCm39) |
M1762K |
probably benign |
Het |
| Sec16a |
A |
G |
2: 26,313,579 (GRCm39) |
V1927A |
probably benign |
Het |
| Sec23a |
G |
T |
12: 59,025,345 (GRCm39) |
A492E |
probably damaging |
Het |
| Skint4 |
T |
A |
4: 111,975,311 (GRCm39) |
H82Q |
probably benign |
Het |
| Srbd1 |
T |
C |
17: 86,446,580 (GRCm39) |
K60E |
probably benign |
Het |
| Stk24 |
A |
G |
14: 121,545,456 (GRCm39) |
Y101H |
probably damaging |
Het |
| Sult1e1 |
A |
T |
5: 87,726,396 (GRCm39) |
N239K |
probably damaging |
Het |
| Tgs1 |
C |
T |
4: 3,604,848 (GRCm39) |
P757S |
probably damaging |
Het |
| Tmc2 |
A |
T |
2: 130,090,650 (GRCm39) |
E665D |
probably damaging |
Het |
| Tmprss15 |
C |
A |
16: 78,875,846 (GRCm39) |
D163Y |
probably benign |
Het |
| Unc13a |
C |
A |
8: 72,101,625 (GRCm39) |
V1009L |
possibly damaging |
Het |
| Unc45b |
G |
T |
11: 82,819,496 (GRCm39) |
G490C |
probably damaging |
Het |
| Vmn1r177 |
T |
A |
7: 23,565,765 (GRCm39) |
H37L |
probably damaging |
Het |
| Vwa5a |
A |
G |
9: 38,645,264 (GRCm39) |
M450V |
possibly damaging |
Het |
| Wars2 |
T |
C |
3: 99,094,843 (GRCm39) |
I46T |
probably benign |
Het |
| Wdfy3 |
G |
T |
5: 101,999,176 (GRCm39) |
T3098K |
possibly damaging |
Het |
| Zan |
A |
T |
5: 137,387,622 (GRCm39) |
I4863N |
unknown |
Het |
| Zfp616 |
A |
G |
11: 73,974,064 (GRCm39) |
|
probably null |
Het |
| Zfp770 |
A |
T |
2: 114,027,514 (GRCm39) |
I185N |
probably damaging |
Het |
| Zfp808 |
T |
G |
13: 62,320,821 (GRCm39) |
H683Q |
probably damaging |
Het |
| Zmym4 |
A |
T |
4: 126,776,275 (GRCm39) |
W1221R |
probably 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 |
|
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 |
|
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'- TCCATTGCACCAGCTCTGGATCAC -3'
(R):5'- ATGTCCAAGATGGGCAACCCCTTC -3'
Sequencing Primer
(F):5'- AGCTCTGGATCACTCTGTAAAC -3'
(R):5'- AGCGGCGATACTTCTACTTG -3'
|
| Posted On |
2014-03-14 |
Incidental Mutation