Incidental Mutation 'R5753:Grk2'
| ID |
444923 |
| 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 |
043358-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5753 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
19 |
| Chromosomal Location |
4336029-4356250 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 4340496 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Histidine
at position 295
(R295H)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000086114
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025791]
[ENSMUST00000088737]
[ENSMUST00000113837]
[ENSMUST00000167511]
[ENSMUST00000171123]
|
| AlphaFold |
Q99MK8 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000025791
AA Change: R253H
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: R253H
| 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: R295H
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: R295H
| 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 |
unknown
Transcript: ENSMUST00000165954
AA Change: R5H
|
| SMART Domains |
Protein: ENSMUSP00000128177
Gene: ENSMUSG00000024858
AA Change: R5H
| 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 |
noncoding transcript
Transcript: ENSMUST00000169991
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000171123
AA Change: R295H
PolyPhen 2
Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
AA Change: R295H
| 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: 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 |
0.1649 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.7%
- 10x: 97.5%
- 20x: 96.0%
|
| Validation Efficiency |
97% (58/60) |
| 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: 55 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2310003L06Rik |
C |
T |
5: 88,120,374 (GRCm39) |
T377I |
probably damaging |
Het |
| Abcb1a |
A |
G |
5: 8,773,160 (GRCm39) |
D796G |
probably damaging |
Het |
| Actn3 |
T |
C |
19: 4,914,595 (GRCm39) |
|
probably null |
Het |
| Ada |
A |
T |
2: 163,577,318 (GRCm39) |
S57T |
probably benign |
Het |
| Adamts6 |
A |
G |
13: 104,483,858 (GRCm39) |
Y359C |
probably damaging |
Het |
| Adcy1 |
A |
T |
11: 7,080,300 (GRCm39) |
I348F |
probably damaging |
Het |
| Ankrd11 |
T |
C |
8: 123,622,043 (GRCm39) |
E603G |
possibly damaging |
Het |
| Bcas3 |
A |
G |
11: 85,712,910 (GRCm39) |
|
probably benign |
Het |
| Cldn1 |
C |
A |
16: 26,181,871 (GRCm39) |
V113L |
probably benign |
Het |
| Dock9 |
T |
C |
14: 121,872,037 (GRCm39) |
T540A |
probably benign |
Het |
| Erp27 |
A |
G |
6: 136,896,875 (GRCm39) |
F109S |
probably damaging |
Het |
| F13a1 |
G |
A |
13: 37,082,082 (GRCm39) |
Q541* |
probably null |
Het |
| Fam124a |
T |
C |
14: 62,843,988 (GRCm39) |
S499P |
probably benign |
Het |
| Fgd3 |
T |
A |
13: 49,428,416 (GRCm39) |
E486V |
possibly damaging |
Het |
| Flnc |
T |
C |
6: 29,433,488 (GRCm39) |
S11P |
probably benign |
Het |
| Gm12508 |
C |
A |
4: 55,254,787 (GRCm39) |
|
noncoding transcript |
Het |
| Gtf2ird1 |
A |
G |
5: 134,439,837 (GRCm39) |
M131T |
probably damaging |
Het |
| H4c4 |
G |
A |
13: 23,765,587 (GRCm39) |
M1I |
probably null |
Het |
| Itpripl2 |
A |
G |
7: 118,090,232 (GRCm39) |
V109A |
probably damaging |
Het |
| Jakmip2 |
T |
C |
18: 43,692,181 (GRCm39) |
E585G |
probably damaging |
Het |
| Kbtbd3 |
A |
T |
9: 4,331,404 (GRCm39) |
I593F |
possibly damaging |
Het |
| Lgr4 |
C |
T |
2: 109,832,857 (GRCm39) |
Q316* |
probably null |
Het |
| Mcf2l |
T |
C |
8: 13,049,993 (GRCm39) |
F305S |
probably damaging |
Het |
| Nos1ap |
T |
A |
1: 170,176,968 (GRCm39) |
K145M |
probably damaging |
Het |
| Or4c3 |
T |
C |
2: 89,851,847 (GRCm39) |
T188A |
possibly damaging |
Het |
| Or4k51 |
T |
A |
2: 111,585,146 (GRCm39) |
I184K |
possibly damaging |
Het |
| Or4q3 |
T |
A |
14: 50,583,045 (GRCm39) |
T285S |
probably damaging |
Het |
| Or51b17 |
A |
G |
7: 103,542,408 (GRCm39) |
L178P |
probably damaging |
Het |
| Or5d18 |
G |
A |
2: 87,864,920 (GRCm39) |
L188F |
probably damaging |
Het |
| Or5w18 |
A |
T |
2: 87,633,596 (GRCm39) |
M288L |
probably benign |
Het |
| Or7a40 |
A |
T |
16: 16,491,484 (GRCm39) |
Y120* |
probably null |
Het |
| Pcdh9 |
T |
A |
14: 94,125,597 (GRCm39) |
D191V |
probably damaging |
Het |
| Pde4d |
T |
A |
13: 109,909,256 (GRCm39) |
|
probably benign |
Het |
| Phkb |
C |
T |
8: 86,604,859 (GRCm39) |
A88V |
probably damaging |
Het |
| Plec |
A |
G |
15: 76,057,620 (GRCm39) |
S4128P |
probably damaging |
Het |
| Plekha5 |
A |
T |
6: 140,482,730 (GRCm39) |
|
probably null |
Het |
| Rgs13 |
A |
C |
1: 144,016,478 (GRCm39) |
N88K |
probably benign |
Het |
| Rho |
T |
A |
6: 115,912,448 (GRCm39) |
I104N |
probably damaging |
Het |
| Rnps1 |
T |
C |
17: 24,637,138 (GRCm39) |
|
probably benign |
Het |
| Saxo5 |
A |
T |
8: 3,534,112 (GRCm39) |
I350L |
probably benign |
Het |
| Slc10a7 |
G |
T |
8: 79,251,928 (GRCm39) |
|
probably null |
Het |
| Slc39a7 |
C |
T |
17: 34,249,150 (GRCm39) |
R246K |
probably damaging |
Het |
| Sort1 |
G |
C |
3: 108,253,090 (GRCm39) |
G510A |
probably damaging |
Het |
| Spag6l |
A |
G |
16: 16,584,831 (GRCm39) |
|
probably null |
Het |
| Sync |
T |
A |
4: 129,187,179 (GRCm39) |
Y70* |
probably null |
Het |
| Timm8a2 |
T |
C |
14: 122,272,289 (GRCm39) |
V64A |
probably benign |
Het |
| Tnfrsf11b |
C |
A |
15: 54,117,455 (GRCm39) |
V267L |
possibly damaging |
Het |
| Trim30b |
A |
G |
7: 104,006,544 (GRCm39) |
V104A |
possibly damaging |
Het |
| Tusc3 |
T |
C |
8: 39,564,100 (GRCm39) |
S244P |
probably damaging |
Het |
| Usp16 |
T |
A |
16: 87,279,787 (GRCm39) |
Y746N |
probably damaging |
Het |
| Vax1 |
G |
T |
19: 59,154,814 (GRCm39) |
H274Q |
probably benign |
Het |
| Vmn2r108 |
A |
G |
17: 20,683,179 (GRCm39) |
V675A |
probably damaging |
Het |
| Vmn2r12 |
A |
T |
5: 109,239,670 (GRCm39) |
W298R |
probably damaging |
Het |
| Zfp948 |
A |
G |
17: 21,807,156 (GRCm39) |
N116S |
probably damaging |
Het |
| Zkscan2 |
A |
G |
7: 123,079,923 (GRCm39) |
V678A |
probably benign |
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 |
|
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'- GGGAACTACATGGTTTTGGGAC -3'
(R):5'- AAGCTCAGCTTCATCCTGG -3'
Sequencing Primer
(F):5'- ACAAGGCCCCAGGTAGG -3'
(R):5'- TCATCCTGGACCTCATGAACGG -3'
|
| Posted On |
2016-11-21 |
Incidental Mutation