Incidental Mutation 'R1240:Grk2'
| ID |
151968 |
| 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 |
039307-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1240 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
19 |
| Chromosomal Location |
4336029-4356250 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 4340707 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Cysteine to Arginine
at position 251
(C251R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000126930
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025791]
[ENSMUST00000088737]
[ENSMUST00000113837]
[ENSMUST00000167511]
[ENSMUST00000171123]
|
| AlphaFold |
Q99MK8 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000025791
AA Change: C209R
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: C209R
| 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: C251R
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: C251R
| 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: C251R
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
AA Change: C251R
| 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: 99.1%
- 3x: 98.3%
- 10x: 96.3%
- 20x: 92.8%
|
| 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: 60 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcb9 |
T |
G |
5: 124,227,984 (GRCm39) |
I86L |
probably benign |
Het |
| Ankfn1 |
A |
G |
11: 89,282,960 (GRCm39) |
L229P |
probably damaging |
Het |
| Aoc1 |
T |
C |
6: 48,882,549 (GRCm39) |
S164P |
probably benign |
Het |
| Arhgef28 |
C |
T |
13: 98,066,000 (GRCm39) |
V1618I |
probably benign |
Het |
| Arpc3 |
T |
C |
5: 122,542,242 (GRCm39) |
F88S |
probably damaging |
Het |
| Asgr2 |
G |
T |
11: 69,987,676 (GRCm39) |
R58L |
possibly damaging |
Het |
| Bach2 |
T |
C |
4: 32,563,198 (GRCm39) |
F432S |
probably damaging |
Het |
| Brms1l |
C |
A |
12: 55,891,293 (GRCm39) |
R116S |
probably damaging |
Het |
| Casp2 |
T |
A |
6: 42,245,879 (GRCm39) |
C179S |
probably damaging |
Het |
| Ccdc73 |
A |
T |
2: 104,821,906 (GRCm39) |
E618D |
probably benign |
Het |
| Cdh6 |
T |
A |
15: 13,057,541 (GRCm39) |
D260V |
possibly damaging |
Het |
| Cenpc1 |
G |
T |
5: 86,183,369 (GRCm39) |
N473K |
probably benign |
Het |
| Chst2 |
T |
C |
9: 95,287,536 (GRCm39) |
E270G |
possibly damaging |
Het |
| Chst9 |
C |
T |
18: 15,586,231 (GRCm39) |
E111K |
probably benign |
Het |
| Cyp3a44 |
T |
G |
5: 145,711,250 (GRCm39) |
I474L |
probably benign |
Het |
| Dbr1 |
G |
T |
9: 99,466,073 (GRCm39) |
E550D |
probably benign |
Het |
| Dph6 |
T |
C |
2: 114,475,199 (GRCm39) |
|
probably null |
Het |
| Fam227b |
T |
A |
2: 125,966,505 (GRCm39) |
I136L |
possibly damaging |
Het |
| Fcgbp |
A |
G |
7: 27,819,950 (GRCm39) |
N2559S |
probably damaging |
Het |
| Fh1 |
A |
T |
1: 175,431,581 (GRCm39) |
I435N |
probably damaging |
Het |
| Gab1 |
A |
C |
8: 81,515,159 (GRCm39) |
S386R |
probably damaging |
Het |
| Gkn1 |
T |
A |
6: 87,326,098 (GRCm39) |
N31Y |
probably damaging |
Het |
| H2-DMa |
G |
T |
17: 34,357,380 (GRCm39) |
|
probably null |
Het |
| Hp1bp3 |
T |
C |
4: 137,957,009 (GRCm39) |
S63P |
probably damaging |
Het |
| Ift74 |
A |
G |
4: 94,581,174 (GRCm39) |
|
probably null |
Het |
| Inf2 |
G |
A |
12: 112,577,210 (GRCm39) |
R1018Q |
unknown |
Het |
| Kat2b |
A |
G |
17: 53,931,425 (GRCm39) |
D141G |
probably benign |
Het |
| Klhl30 |
T |
C |
1: 91,288,737 (GRCm39) |
S499P |
probably benign |
Het |
| Lama2 |
A |
C |
10: 26,917,120 (GRCm39) |
D2268E |
probably damaging |
Het |
| Lsmem1 |
GTACATACATACATACATACATACATACA |
GTACATACATACATACATACATACATACATACA |
12: 40,235,260 (GRCm39) |
|
probably null |
Het |
| Marf1 |
T |
C |
16: 13,964,626 (GRCm39) |
N258S |
possibly damaging |
Het |
| Mc1r |
T |
A |
8: 124,134,999 (GRCm39) |
C251S |
probably damaging |
Het |
| Myo15b |
C |
A |
11: 115,771,327 (GRCm39) |
Q257K |
possibly damaging |
Het |
| Nbeal2 |
A |
G |
9: 110,456,176 (GRCm39) |
F2431S |
probably damaging |
Het |
| Neb |
T |
A |
2: 52,186,321 (GRCm39) |
H917L |
possibly damaging |
Het |
| Nlrp1a |
A |
G |
11: 71,004,292 (GRCm39) |
|
probably null |
Het |
| Nr1d2 |
A |
T |
14: 18,211,891 (GRCm38) |
M404K |
probably benign |
Het |
| Or4b1d |
T |
G |
2: 89,969,157 (GRCm39) |
I109L |
possibly damaging |
Het |
| Or8u8 |
T |
G |
2: 86,012,453 (GRCm39) |
M1L |
possibly damaging |
Het |
| Otoa |
T |
C |
7: 120,755,713 (GRCm39) |
S1040P |
probably benign |
Het |
| Pctp |
T |
C |
11: 89,893,640 (GRCm39) |
D10G |
probably benign |
Het |
| Pja2 |
G |
T |
17: 64,616,613 (GRCm39) |
T94K |
probably benign |
Het |
| Plxna1 |
C |
T |
6: 89,298,032 (GRCm39) |
V1749M |
probably damaging |
Het |
| Prdm15 |
C |
T |
16: 97,638,800 (GRCm39) |
E87K |
probably damaging |
Het |
| Rgsl1 |
A |
G |
1: 153,660,937 (GRCm39) |
F1028L |
probably benign |
Het |
| Sepsecs |
T |
C |
5: 52,818,021 (GRCm39) |
N252S |
probably damaging |
Het |
| Skint5 |
A |
T |
4: 113,574,304 (GRCm39) |
L749Q |
unknown |
Het |
| Slc22a22 |
G |
A |
15: 57,114,268 (GRCm39) |
S353F |
probably benign |
Het |
| Slc49a4 |
A |
G |
16: 35,518,379 (GRCm39) |
F445L |
probably benign |
Het |
| Slc7a13 |
A |
T |
4: 19,819,212 (GRCm39) |
K137N |
probably damaging |
Het |
| Snx13 |
G |
T |
12: 35,141,405 (GRCm39) |
V163L |
probably damaging |
Het |
| Synrg |
A |
T |
11: 83,914,182 (GRCm39) |
T1115S |
probably damaging |
Het |
| Tenm3 |
A |
G |
8: 48,740,928 (GRCm39) |
V1185A |
possibly damaging |
Het |
| Tent5b |
T |
C |
4: 133,213,815 (GRCm39) |
F229L |
probably benign |
Het |
| Tg |
T |
A |
15: 66,700,397 (GRCm39) |
N118K |
probably benign |
Het |
| Top1mt |
T |
C |
15: 75,541,916 (GRCm39) |
K153E |
probably damaging |
Het |
| Trmt11 |
T |
C |
10: 30,466,821 (GRCm39) |
|
probably benign |
Het |
| Unc80 |
A |
G |
1: 66,675,061 (GRCm39) |
D1953G |
possibly damaging |
Het |
| Vmn2r25 |
T |
A |
6: 123,828,864 (GRCm39) |
S137C |
probably damaging |
Het |
| Vwf |
C |
A |
6: 125,580,271 (GRCm39) |
|
probably null |
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 |
|
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 |
|
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'- ACTCCATGCTGAGACAGGTGGTAG -3'
(R):5'- TGCGCTCTCTAAAGCACTGGTTG -3'
Sequencing Primer
(F):5'- CAGGTGGTAGTGCAGGTCC -3'
(R):5'- CTAAAGCACTGGTTGTGTCAC -3'
|
| Posted On |
2014-01-29 |
Incidental Mutation