Mutagenetix > Incidental Mutation

Incidental Mutation 'R0494:Grk2'

42703

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

038691-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0494 (G1)

Quality Score

212

Status

Validated

Chromosome

Chromosomal Location

4336029-4356250 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 4341347 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Lysine at position 189 (N189K)

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: N147K

PolyPhen 2 Score 0.843 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000025791
Gene: ENSMUSG00000024858
AA Change: N147K

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: N189K

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000086114
Gene: ENSMUSG00000024858
AA Change: N189K

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: N189K

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000126930
Gene: ENSMUSG00000024858
AA Change: N189K

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

Meta Mutation Damage Score

0.1287

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.5%
20x: 93.1%

Validation Efficiency

97% (109/112)

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: 108 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aatf	T	C	11: 84,402,339 (GRCm39)	I116V	probably benign	Het
Abhd18	T	C	3: 40,871,123 (GRCm39)	F94S	probably damaging	Het
Adam28	T	A	14: 68,868,241 (GRCm39)		probably benign	Het
Afg2a	G	C	3: 37,486,312 (GRCm39)	D345H	possibly damaging	Het
Amn1	A	T	6: 149,086,634 (GRCm39)		probably benign	Het
Arhgap32	T	C	9: 32,170,199 (GRCm39)	V993A	probably damaging	Het
Arhgap33	A	T	7: 30,223,921 (GRCm39)	S703T	probably damaging	Het
Arhgef1	T	C	7: 24,618,785 (GRCm39)		probably benign	Het
Atg2a	A	G	19: 6,303,407 (GRCm39)	Y1083C	probably damaging	Het
Atp2a3	T	C	11: 72,872,731 (GRCm39)	F760L	probably damaging	Het
B9d1	A	G	11: 61,403,271 (GRCm39)		probably benign	Het
Batf	C	T	12: 85,733,636 (GRCm39)		probably benign	Het
BC051019	T	A	7: 109,317,182 (GRCm39)	Y170F	probably benign	Het
Bphl	T	C	13: 34,221,754 (GRCm39)	*37Q	probably null	Het
Cab39l	T	C	14: 59,737,008 (GRCm39)	S43P	probably damaging	Het
Cad	A	G	5: 31,234,856 (GRCm39)		probably benign	Het
Cct4	T	G	11: 22,946,014 (GRCm39)	S119A	probably benign	Het
Cd163	G	A	6: 124,288,408 (GRCm39)	V280M	probably damaging	Het
Cd86	A	G	16: 36,438,999 (GRCm39)		probably benign	Het
Cdh23	G	A	10: 60,152,375 (GRCm39)		probably benign	Het
Cdhr5	A	G	7: 140,852,431 (GRCm39)	F145S	probably damaging	Het
Cdt1	T	C	8: 123,298,799 (GRCm39)	S479P	possibly damaging	Het
Ces2g	T	C	8: 105,693,199 (GRCm39)	V372A	probably benign	Het
Chrna3	T	C	9: 54,929,562 (GRCm39)	D92G	probably damaging	Het
Cndp1	A	G	18: 84,637,658 (GRCm39)	S359P	probably benign	Het
Cops4	A	G	5: 100,676,528 (GRCm39)	Q93R	probably damaging	Het
Dgka	G	C	10: 128,556,952 (GRCm39)		probably benign	Het
Dmp1	A	T	5: 104,360,074 (GRCm39)	D250V	probably damaging	Het
Dnajb2	C	T	1: 75,216,278 (GRCm39)		probably benign	Het
Dock9	T	C	14: 121,899,996 (GRCm39)	T113A	possibly damaging	Het
Egln3	T	A	12: 54,250,107 (GRCm39)	I81F	probably benign	Het
Elapor2	G	A	5: 9,470,723 (GRCm39)		probably null	Het
Elovl5	T	C	9: 77,868,199 (GRCm39)	V37A	probably benign	Het
Esco1	A	T	18: 10,594,940 (GRCm39)	N115K	probably benign	Het
Fat1	A	T	8: 45,403,579 (GRCm39)	N110I	probably damaging	Het
Fezf1	T	A	6: 23,246,054 (GRCm39)	K370N	probably damaging	Het
Galnt18	T	A	7: 111,153,771 (GRCm39)	K284N	probably damaging	Het
Glt8d1	C	A	14: 30,733,580 (GRCm39)	T355K	possibly damaging	Het
Gm17455	G	A	10: 60,239,014 (GRCm39)	R93H	possibly damaging	Het
Gng8	T	A	7: 16,629,213 (GRCm39)	D46E	probably benign	Het
Gpx4	T	C	10: 79,892,011 (GRCm39)		probably benign	Het
Grm5	T	C	7: 87,779,989 (GRCm39)	V1143A	probably benign	Het
Hibch	A	G	1: 52,942,055 (GRCm39)	E237G	possibly damaging	Het
Hipk2	C	T	6: 38,706,924 (GRCm39)	A682T	probably benign	Het
Hmcn1	G	T	1: 150,608,543 (GRCm39)		probably benign	Het
Htt	A	G	5: 34,979,188 (GRCm39)	D857G	possibly damaging	Het
Idh2	C	T	7: 79,748,005 (GRCm39)	A232T	probably damaging	Het
Igsf8	A	G	1: 172,146,265 (GRCm39)	E421G	probably benign	Het
Kif26a	T	A	12: 112,145,905 (GRCm39)		probably null	Het
Klhl26	T	C	8: 70,904,251 (GRCm39)	Y519C	probably damaging	Het
Lamc1	A	C	1: 153,122,682 (GRCm39)		probably null	Het
Mical3	A	T	6: 120,936,162 (GRCm39)	S1455T	possibly damaging	Het
Mitf	G	A	6: 97,971,390 (GRCm39)	G186S	probably benign	Het
Ms4a15	G	A	19: 10,958,722 (GRCm39)		probably benign	Het
Myo5b	A	G	18: 74,787,038 (GRCm39)	E481G	probably damaging	Het
Nanos3	C	T	8: 84,902,763 (GRCm39)	R133Q	probably damaging	Het
Nbeal2	C	A	9: 110,456,255 (GRCm39)	V1686L	probably damaging	Het
Nedd4l	T	G	18: 65,306,092 (GRCm39)	S335A	possibly damaging	Het
Nos1	A	T	5: 118,043,539 (GRCm39)	N605Y	probably damaging	Het
Nyx	C	A	X: 13,353,508 (GRCm39)	T454K	probably benign	Het
Or52n2	A	G	7: 104,542,478 (GRCm39)	L119P	probably damaging	Het
Or8g55	T	A	9: 39,784,698 (GRCm39)	N42K	probably damaging	Het
Pcdhb12	T	A	18: 37,571,148 (GRCm39)	F765I	probably benign	Het
Pex3	C	T	10: 13,403,532 (GRCm39)	G330R	probably damaging	Het
Pfkfb1	T	C	X: 149,417,609 (GRCm39)	Y339H	probably damaging	Het
Pias1	G	A	9: 62,794,593 (GRCm39)	Q26*	probably null	Het
Pik3cg	C	A	12: 32,254,545 (GRCm39)	V481L	possibly damaging	Het
Plcg2	C	T	8: 118,282,843 (GRCm39)	T108M	probably damaging	Het
Pon2	G	A	6: 5,267,059 (GRCm39)		probably benign	Het
Ppef2	A	T	5: 92,400,952 (GRCm39)		probably benign	Het
Pramel21	G	T	4: 143,342,726 (GRCm39)	V278F	probably benign	Het
Ptpn22	A	G	3: 103,767,771 (GRCm39)	K18E	probably damaging	Het
Pum2	C	T	12: 8,771,736 (GRCm39)	Q360*	probably null	Het
Rab10	A	C	12: 3,302,723 (GRCm39)		probably null	Het
Ranbp2	T	G	10: 58,303,254 (GRCm39)	S809A	possibly damaging	Het
Rbms2	A	G	10: 127,969,539 (GRCm39)	V348A	probably benign	Het
Rnf213	A	G	11: 119,316,838 (GRCm39)	E988G	possibly damaging	Het
Rnf213	A	T	11: 119,333,946 (GRCm39)	M3052L	probably damaging	Het
Rpl14	C	A	9: 120,403,428 (GRCm39)		probably benign	Het
Rplp0	A	G	5: 115,697,931 (GRCm39)	Y13C	possibly damaging	Het
Ryr1	A	G	7: 28,703,218 (GRCm39)		probably benign	Het
Sac3d1	T	C	19: 6,168,324 (GRCm39)	E98G	probably damaging	Het
Scn10a	T	A	9: 119,453,166 (GRCm39)	D1242V	probably damaging	Het
Scnn1b	T	C	7: 121,498,681 (GRCm39)	Y74H	probably damaging	Het
Serpinb3a	C	T	1: 106,975,212 (GRCm39)	W198*	probably null	Het
Sf3b4	C	A	3: 96,081,017 (GRCm39)	D108E	probably damaging	Het
Shprh	T	C	10: 11,032,935 (GRCm39)	V307A	probably damaging	Het
Slc2a2	A	G	3: 28,781,426 (GRCm39)	D458G	probably benign	Het
Strc	T	C	2: 121,210,014 (GRCm39)	D103G	probably damaging	Het
Synrg	T	C	11: 83,910,369 (GRCm39)	I923T	probably benign	Het
Tango6	G	T	8: 107,462,314 (GRCm39)		probably benign	Het
Tas2r106	A	G	6: 131,655,539 (GRCm39)	L104P	probably damaging	Het
Tat	C	T	8: 110,718,316 (GRCm39)	P67L	probably damaging	Het
Tln2	A	C	9: 67,262,479 (GRCm39)	S593A	probably benign	Het
Tmem94	A	G	11: 115,685,607 (GRCm39)		probably null	Het
Tppp3	G	A	8: 106,194,804 (GRCm39)	A109V	probably benign	Het
Trank1	T	C	9: 111,220,361 (GRCm39)	F2366S	probably benign	Het
Trpc5	T	A	X: 143,264,392 (GRCm39)	Y155F	probably damaging	Het
Trpv1	A	G	11: 73,151,268 (GRCm39)	T451A	probably benign	Het
Ttc9	C	A	12: 81,678,423 (GRCm39)	A82E	probably damaging	Het
Ttll11	T	A	2: 35,834,886 (GRCm39)	N180I	probably damaging	Het
Ttn	T	C	2: 76,566,743 (GRCm39)	N28050S	possibly damaging	Het
Vmn2r73	G	T	7: 85,522,140 (GRCm39)	H66Q	probably benign	Het
Vmn2r92	C	T	17: 18,388,219 (GRCm39)	A408V	probably damaging	Het
Wnt3	G	A	11: 103,703,141 (GRCm39)	C208Y	probably damaging	Het
Zfp521	C	A	18: 13,978,325 (GRCm39)	C696F	probably damaging	Het
Zfp521	T	C	18: 13,979,927 (GRCm39)	D162G	probably damaging	Het
Zfp869	A	T	8: 70,159,054 (GRCm39)	H506Q	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
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
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'- ACTTGTAGGCAGAGACTCAGGGATG -3'
(R):5'- TGCAGCAGGACAACATGGTTCAG -3'

Sequencing Primer
(F):5'- AAGCTTGGGACACTGATCC -3'
(R):5'- GTGACAAGTTCACACGGTTC -3'

Posted On

2013-05-23