Mutagenetix > Incidental Mutation

Incidental Mutation 'R0833:Grk2'

77689

Institutional Source

Beutler Lab

Gene Symbol

Grk2

Ensembl Gene

ENSMUSG00000024858

Gene Name

G protein-coupled receptor kinase 2

Synonyms

Adrbk-1, beta-adrenergic receptor kinase-1, beta-AR kinase-1, Bark-1, beta ARK, beta ARK1, betaARK1, Adrbk1

MMRRC Submission

039012-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0833 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

4286001-4306222 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 4289357 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Phenylalanine at position 428 (L428F)

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: L386F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: L386F

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: L428F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: L428F

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: L143F

SMART Domains

Protein: ENSMUSP00000128177
Gene: ENSMUSG00000024858
AA Change: L143F

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

unknown
Transcript: ENSMUST00000168594
AA Change: L12F

SMART Domains

Protein: ENSMUSP00000126025
Gene: ENSMUSG00000024858
AA Change: L12F

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

noncoding transcript
Transcript: ENSMUST00000169991

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

Meta Mutation Damage Score

0.4884

Coding Region Coverage

1x: 99.4%
3x: 98.8%
10x: 97.3%
20x: 94.6%

Validation Efficiency

100% (97/97)

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700113H08Rik	T	C	10: 87,165,069	L41P	probably damaging	Het
3110082I17Rik	A	G	5: 139,364,120	V58A	possibly damaging	Het
4932415M13Rik	A	T	17: 53,724,346		noncoding transcript	Het
Aldh1a7	C	T	19: 20,702,243	V390M	probably damaging	Het
Alg14	A	G	3: 121,298,610	H34R	probably damaging	Het
Ankrd27	A	G	7: 35,608,347	N337S	probably damaging	Het
Apoa2	T	A	1: 171,225,379		probably benign	Het
Arl2	T	G	19: 6,136,022	K126T	probably damaging	Het
Ascc3	T	C	10: 50,845,666	W2072R	probably benign	Het
Astl	T	C	2: 127,342,419	F21L	probably benign	Het
Asxl3	A	G	18: 22,516,040	D362G	probably damaging	Het
Bdp1	A	T	13: 100,035,825	H2094Q	probably benign	Het
Cacna2d4	C	T	6: 119,307,286	R745W	probably damaging	Het
Cbwd1	A	G	19: 24,940,839		probably benign	Het
Ccdc144b	A	G	3: 36,020,213		probably benign	Het
Ccdc85a	T	A	11: 28,583,296	I83F	probably damaging	Het
Ccnt2	T	A	1: 127,802,394	M336K	probably benign	Het
Cd226	A	C	18: 89,207,020		probably benign	Het
Ces1f	A	T	8: 93,270,024	S214T	probably damaging	Het
Clip1	T	C	5: 123,630,721	D605G	probably benign	Het
Col26a1	A	G	5: 136,765,300		probably null	Het
Crtc1	A	G	8: 70,393,013	V306A	probably benign	Het
D130043K22Rik	G	A	13: 24,863,580		probably benign	Het
D17H6S53E	A	T	17: 35,127,409		probably null	Het
D17Wsu92e	A	T	17: 27,786,138	S148R	probably damaging	Het
Dnah11	G	A	12: 118,196,662	A111V	probably benign	Het
Dyrk2	T	C	10: 118,861,122	H77R	probably benign	Het
E330017A01Rik	G	A	16: 58,635,523	S129L	probably damaging	Het
Epha3	A	G	16: 63,603,519		probably benign	Het
Epn2	T	C	11: 61,519,491	N611S	probably benign	Het
Erich6	A	C	3: 58,618,944		probably benign	Het
Fam217b	T	C	2: 178,420,989	S249P	probably benign	Het
Fam219b	A	G	9: 57,538,016		probably benign	Het
Fryl	A	T	5: 73,089,081		probably benign	Het
Gm12800	G	A	4: 101,910,097	C181Y	probably damaging	Het
Gm13089	A	T	4: 143,698,486	M129K	probably benign	Het
Gm14496	T	C	2: 181,996,266	W378R	probably damaging	Het
Gm5155	C	A	7: 17,904,981	A301E	possibly damaging	Het
Gm8674	A	T	13: 49,904,575		noncoding transcript	Het
Grap	T	A	11: 61,660,239	D32E	possibly damaging	Het
Grm8	T	A	6: 27,363,179	E779V	probably damaging	Het
Hipk1	A	G	3: 103,754,296	S670P	probably damaging	Het
Itgae	A	T	11: 73,129,206	M845L	probably benign	Het
Itih1	A	T	14: 30,941,555	V164E	probably damaging	Het
Itpka	T	A	2: 119,750,831	N448K	probably damaging	Het
Jak3	A	C	8: 71,683,978	N643T	probably damaging	Het
Lrfn5	A	C	12: 61,839,668	T81P	probably damaging	Het
Lrrc45	T	A	11: 120,718,193		probably null	Het
March6	T	C	15: 31,480,291	Y562C	probably benign	Het
Mcrs1	T	C	15: 99,243,449		probably benign	Het
Meis1	G	A	11: 18,881,767	H424Y	possibly damaging	Het
Mst1r	G	A	9: 107,913,167	V660I	probably benign	Het
Mst1r	A	G	9: 107,914,776	N837S	probably benign	Het
Mthfd2l	T	C	5: 90,946,942	V90A	probably damaging	Het
Mtnr1a	A	T	8: 45,087,937	I312F	probably benign	Het
Olfr1513	T	C	14: 52,349,378	I223V	probably benign	Het
Olfr578	C	A	7: 102,984,836	L109F	possibly damaging	Het
Olfr875	T	C	9: 37,773,076	V139A	probably benign	Het
Otog	C	T	7: 46,269,362	T954I	possibly damaging	Het
Pdcd6	A	G	13: 74,316,324		probably benign	Het
Phlpp2	A	G	8: 109,937,106	T926A	probably damaging	Het
Plec	GGCAGCAG	GGCAGCAGCAG	15: 76,181,907		probably benign	Het
Plekha5	T	A	6: 140,589,634		probably benign	Het
Ppp1r16a	C	T	15: 76,693,669	Q328*	probably null	Het
Rab27b	T	C	18: 69,987,041		probably benign	Het
Rapsn	T	C	2: 91,036,808	Y152H	probably damaging	Het
Rasd1	A	T	11: 59,964,553	F85I	probably damaging	Het
Rgs1	A	T	1: 144,247,933	S85T	probably damaging	Het
Samd9l	T	C	6: 3,372,725	E1512G	possibly damaging	Het
Sgsm1	C	T	5: 113,279,184	A127T	probably benign	Het
Shc1	A	G	3: 89,422,969	D70G	probably damaging	Het
Slc26a1	T	A	5: 108,673,523	T167S	probably benign	Het
Slc26a7	A	T	4: 14,593,873	Y81N	probably damaging	Het
Slc2a12	T	C	10: 22,702,016		probably benign	Het
Slc30a7	T	A	3: 115,990,140		probably null	Het
Slc44a5	T	C	3: 154,265,474	S654P	probably damaging	Het
Stard9	T	G	2: 120,696,999	S1246A	possibly damaging	Het
Stxbp5	A	T	10: 9,865,099	S116R	probably damaging	Het
Syvn1	C	T	19: 6,052,453	P517L	probably benign	Het
Tas2r105	T	C	6: 131,687,430	I12V	probably benign	Het
Tas2r121	A	G	6: 132,700,362	S216P	probably damaging	Het
Tcof1	T	C	18: 60,845,832	D48G	probably damaging	Het
Tgm3	C	T	2: 130,026,682		probably benign	Het
Tle2	T	C	10: 81,588,947	F667L	probably damaging	Het
Tnfaip3	C	A	10: 19,002,949	A704S	probably benign	Het
Trabd2b	A	G	4: 114,580,322	Q232R	probably benign	Het
Ttc28	T	A	5: 111,231,081	I1144N	probably damaging	Het
Ucp3	T	A	7: 100,479,541	C25*	probably null	Het
Ugt3a2	A	G	15: 9,370,150	D460G	probably damaging	Het
Urb1	T	C	16: 90,795,448	D308G	possibly damaging	Het
Ush1g	G	T	11: 115,318,868	R167S	possibly damaging	Het
Vav3	A	G	3: 109,647,679	N81S	possibly damaging	Het
Vmn2r108	A	T	17: 20,471,459	D267E	probably benign	Het

Other mutations in Grk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00757:Grk2	APN	19	4289311	critical splice donor site	probably null
IGL00927:Grk2	APN	19	4287954	missense	probably benign	0.09
IGL01465:Grk2	APN	19	4290858	missense	probably damaging	1.00
IGL02692:Grk2	APN	19	4290688	splice site	probably benign
IGL02870:Grk2	APN	19	4290402	missense	probably damaging	1.00
IGL03210:Grk2	APN	19	4287829	missense	probably benign	0.01
IGL03227:Grk2	APN	19	4287829	missense	probably benign	0.01
IGL03230:Grk2	APN	19	4287829	missense	probably benign	0.01
Greco	UTSW	19	4290602	critical splice donor site	probably null
PIT4480001:Grk2	UTSW	19	4287409	missense	possibly damaging	0.93
R0008:Grk2	UTSW	19	4287234	missense	probably damaging	0.99
R0371:Grk2	UTSW	19	4291586	splice site	probably null
R0426:Grk2	UTSW	19	4290600	splice site	probably null
R0494:Grk2	UTSW	19	4291319	missense	probably damaging	1.00
R1240:Grk2	UTSW	19	4290679	missense	probably damaging	1.00
R1446:Grk2	UTSW	19	4287409	missense	possibly damaging	0.93
R1499:Grk2	UTSW	19	4287194	missense	probably benign	0.11
R1664:Grk2	UTSW	19	4287240	missense	possibly damaging	0.48
R1796:Grk2	UTSW	19	4287940	missense	probably benign	0.12
R1803:Grk2	UTSW	19	4294883	missense	probably damaging	1.00
R2021:Grk2	UTSW	19	4290670	missense	probably damaging	1.00
R3947:Grk2	UTSW	19	4292417	missense	possibly damaging	0.95
R4551:Grk2	UTSW	19	4286056	missense	possibly damaging	0.96
R4945:Grk2	UTSW	19	4290447	missense	probably damaging	1.00
R5299:Grk2	UTSW	19	4292771	missense	probably damaging	1.00
R5753:Grk2	UTSW	19	4290468	missense	probably damaging	1.00
R5754:Grk2	UTSW	19	4290468	missense	probably damaging	1.00
R5973:Grk2	UTSW	19	4287897	missense	possibly damaging	0.88
R6026:Grk2	UTSW	19	4290783	missense	probably damaging	0.99
R7117:Grk2	UTSW	19	4290602	critical splice donor site	probably null
R7468:Grk2	UTSW	19	4306035	start gained	probably benign
R7764:Grk2	UTSW	19	4287363	missense	probably damaging	1.00
R8250:Grk2	UTSW	19	4289934	missense	probably damaging	1.00
R8789:Grk2	UTSW	19	4288483	missense	probably damaging	1.00
R9468:Grk2	UTSW	19	4294924	missense	probably damaging	1.00
R9508:Grk2	UTSW	19	4291608	missense	probably damaging	1.00
R9526:Grk2	UTSW	19	4290843	missense	probably damaging	1.00
R9694:Grk2	UTSW	19	4288483	missense	probably damaging	1.00
X0009:Grk2	UTSW	19	4291589	critical splice donor site	probably null
Z1176:Grk2	UTSW	19	4287645	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- CGACACAACCACTGTTCTAAGGGG -3'
(R):5'- ACAAGCATGAGATTGACCGCATGAC -3'

Sequencing Primer
(F):5'- TGTTCTAAGGGGGCACAGC -3'
(R):5'- AGAAGCATAAACTCCTGGTTCTCTC -3'

Posted On

2013-10-16