Incidental Mutation 'P0005:Prkg2'
| ID |
7618 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Prkg2
|
| Ensembl Gene |
ENSMUSG00000029334 |
| Gene Name |
protein kinase, cGMP-dependent, type II |
| Synonyms |
cGK-II, Prkgr2 |
| MMRRC Submission |
038262-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.196)
|
| Stock # |
P0005 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
99077632-99185042 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to C
at 99117806 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Phenylalanine to Valine
at position 512
(F512V)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000124963
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000031277]
[ENSMUST00000161490]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000031277
AA Change: F483V
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000031277
Gene: ENSMUSG00000029334
AA Change: F483V
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
19 |
85 |
N/A |
INTRINSIC |
|
cNMP
|
168 |
284 |
2.82e-19 |
SMART |
|
cNMP
|
286 |
409 |
3.02e-28 |
SMART |
|
S_TKc
|
424 |
682 |
9.46e-75 |
SMART |
|
S_TK_X
|
683 |
733 |
9.83e-4 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000160765
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000161490
AA Change: F512V
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000124963
Gene: ENSMUSG00000029334
AA Change: F512V
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
19 |
85 |
N/A |
INTRINSIC |
|
cNMP
|
168 |
284 |
2.82e-19 |
SMART |
|
cNMP
|
286 |
409 |
3.02e-28 |
SMART |
|
S_TKc
|
453 |
711 |
1.19e-89 |
SMART |
|
S_TK_X
|
712 |
762 |
9.83e-4 |
SMART |
|
| Meta Mutation Damage Score |
0.4734 |
| Coding Region Coverage |
- 1x: 85.5%
- 3x: 80.5%
- 10x: 66.1%
- 20x: 49.6%
|
| Validation Efficiency |
95% (104/109) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that belongs to the serine/threonine protein kinase family of proteins. The encoded protein plays a role in the regulation of fluid balance in the intestine. A similar protein in mouse is thought to regulate differentiation and proliferation of cells in the colon. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
PHENOTYPE: Homozygous null mice exhibit dwarfism, with abnormal skull morphology and short limbs and vertebrae. Defects in axial organization of the growth plates was evident as mice aged. Digestive secretion in response to enterotoxin was reduced. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(4) : Targeted(3) Gene trapped(1)
|
| Other mutations in this stock |
Total: 20 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atp13a1 |
T |
C |
8: 70,256,397 (GRCm39) |
V845A |
possibly damaging |
Het |
| Casp6 |
T |
C |
3: 129,705,792 (GRCm39) |
V153A |
probably benign |
Het |
| Col6a1 |
A |
G |
10: 76,553,163 (GRCm39) |
|
probably benign |
Het |
| Dars2 |
A |
G |
1: 160,881,509 (GRCm39) |
|
probably null |
Het |
| Hmgcll1 |
T |
A |
9: 75,982,041 (GRCm39) |
M162K |
possibly damaging |
Het |
| Hydin |
A |
T |
8: 111,220,921 (GRCm39) |
|
probably null |
Het |
| Ift74 |
A |
G |
4: 94,550,813 (GRCm39) |
|
probably benign |
Het |
| Itpr1 |
A |
T |
6: 108,358,218 (GRCm39) |
I595F |
probably damaging |
Het |
| Mgat4f |
T |
A |
1: 134,315,646 (GRCm39) |
M15K |
probably benign |
Het |
| Mmp17 |
T |
C |
5: 129,673,695 (GRCm39) |
V258A |
probably benign |
Het |
| Nek6 |
T |
C |
2: 38,459,749 (GRCm39) |
|
probably null |
Het |
| Nomo1 |
A |
T |
7: 45,686,981 (GRCm39) |
|
probably null |
Het |
| Nudt3 |
A |
G |
17: 27,815,689 (GRCm39) |
|
probably benign |
Het |
| Pramel32 |
A |
G |
4: 88,546,187 (GRCm39) |
L385P |
probably damaging |
Het |
| Ptp4a3 |
T |
A |
15: 73,627,160 (GRCm39) |
D72E |
possibly damaging |
Het |
| Rpgrip1l |
A |
T |
8: 92,025,853 (GRCm39) |
|
probably benign |
Het |
| Rrp9 |
G |
A |
9: 106,358,376 (GRCm39) |
R101H |
probably benign |
Het |
| Slc7a6os |
T |
C |
8: 106,931,154 (GRCm39) |
I161V |
probably benign |
Het |
| Tex15 |
T |
C |
8: 34,060,896 (GRCm39) |
F109L |
probably benign |
Het |
| Tns2 |
A |
G |
15: 102,022,491 (GRCm39) |
Q1188R |
probably damaging |
Het |
|
| Other mutations in Prkg2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00420:Prkg2
|
APN |
5 |
99,172,400 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01063:Prkg2
|
APN |
5 |
99,117,795 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02060:Prkg2
|
APN |
5 |
99,172,374 (GRCm39) |
missense |
probably benign |
0.32 |
|
IGL02666:Prkg2
|
APN |
5 |
99,145,378 (GRCm39) |
splice site |
probably benign |
|
|
IGL02992:Prkg2
|
APN |
5 |
99,172,365 (GRCm39) |
missense |
probably benign |
|
|
IGL03040:Prkg2
|
APN |
5 |
99,120,966 (GRCm39) |
critical splice donor site |
probably null |
|
|
devito
|
UTSW |
5 |
99,114,369 (GRCm39) |
critical splice donor site |
probably null |
|
|
Goldwyn
|
UTSW |
5 |
99,090,067 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
kilmer
|
UTSW |
5 |
99,095,333 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Pulp
|
UTSW |
5 |
99,124,321 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
travolta
|
UTSW |
5 |
99,117,839 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0044:Prkg2
|
UTSW |
5 |
99,120,989 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0044:Prkg2
|
UTSW |
5 |
99,120,989 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0115:Prkg2
|
UTSW |
5 |
99,142,514 (GRCm39) |
splice site |
probably null |
|
|
R0403:Prkg2
|
UTSW |
5 |
99,142,504 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R0452:Prkg2
|
UTSW |
5 |
99,145,379 (GRCm39) |
splice site |
probably benign |
|
|
R0481:Prkg2
|
UTSW |
5 |
99,142,514 (GRCm39) |
splice site |
probably null |
|
|
R1194:Prkg2
|
UTSW |
5 |
99,119,785 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1534:Prkg2
|
UTSW |
5 |
99,142,420 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1861:Prkg2
|
UTSW |
5 |
99,095,275 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2010:Prkg2
|
UTSW |
5 |
99,172,664 (GRCm39) |
missense |
probably benign |
|
|
R2031:Prkg2
|
UTSW |
5 |
99,172,310 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
R2176:Prkg2
|
UTSW |
5 |
99,114,368 (GRCm39) |
splice site |
probably benign |
|
|
R3607:Prkg2
|
UTSW |
5 |
99,095,236 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3958:Prkg2
|
UTSW |
5 |
99,145,354 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R3960:Prkg2
|
UTSW |
5 |
99,145,354 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R4012:Prkg2
|
UTSW |
5 |
99,127,674 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R4794:Prkg2
|
UTSW |
5 |
99,114,492 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4840:Prkg2
|
UTSW |
5 |
99,129,002 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4867:Prkg2
|
UTSW |
5 |
99,172,568 (GRCm39) |
missense |
probably benign |
0.21 |
|
R5182:Prkg2
|
UTSW |
5 |
99,172,568 (GRCm39) |
missense |
probably benign |
0.21 |
|
R5226:Prkg2
|
UTSW |
5 |
99,124,321 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R5274:Prkg2
|
UTSW |
5 |
99,117,850 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5416:Prkg2
|
UTSW |
5 |
99,091,326 (GRCm39) |
missense |
probably benign |
0.05 |
|
R5531:Prkg2
|
UTSW |
5 |
99,115,593 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5619:Prkg2
|
UTSW |
5 |
99,136,156 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6264:Prkg2
|
UTSW |
5 |
99,082,223 (GRCm39) |
missense |
probably benign |
0.22 |
|
R6925:Prkg2
|
UTSW |
5 |
99,114,369 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7971:Prkg2
|
UTSW |
5 |
99,079,873 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8210:Prkg2
|
UTSW |
5 |
99,114,393 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8788:Prkg2
|
UTSW |
5 |
99,117,839 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8824:Prkg2
|
UTSW |
5 |
99,090,067 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R8825:Prkg2
|
UTSW |
5 |
99,090,043 (GRCm39) |
missense |
probably benign |
0.02 |
|
R8932:Prkg2
|
UTSW |
5 |
99,095,299 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R8950:Prkg2
|
UTSW |
5 |
99,119,815 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R9026:Prkg2
|
UTSW |
5 |
99,114,386 (GRCm39) |
missense |
probably benign |
|
|
R9210:Prkg2
|
UTSW |
5 |
99,095,333 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9363:Prkg2
|
UTSW |
5 |
99,172,257 (GRCm39) |
missense |
probably benign |
0.30 |
|
R9627:Prkg2
|
UTSW |
5 |
99,079,869 (GRCm39) |
makesense |
probably null |
|
|
Z1088:Prkg2
|
UTSW |
5 |
99,172,663 (GRCm39) |
missense |
probably benign |
0.00 |
|
| Protein Function and Prediction |
Prkg2 is a serine/threonine cGMP-dependent kinase (cGK) that is (along with other cGKs such as Prkg1) a down stream effector of the NO/cGMP and the ANP/cGMP pathways [(1;2); reviewed in (3)]. Prkg2 functions to inhibit renin sectretion (4), chloride/water secretion in the small intestine (5), endochondreal bone growth, the control of anxiety-like behavior (6), and control the behavioral effects of ethanol (6).
|
| Expression/Localization |
Prkg2 is predominantly expressed in the secretory epithelium of the small intestine, the juxta-glomerular cells, the adrenal cortex, the chondrocytes, and the lung. Prkg2 is anchored to the plasma membrane by myristoylation at the N-terminus (3).
|
| Background |
Mutations in PRKG2 are associated with Chromosome 4q21 deletion syndrome (OMIM:613509). Patients with this condition have growth restriction, psychomotor retardation, muscle hypotonia, delays in speech, and bilateral sensorineural deafness with bilateral ear canal stenosis (7-9)
Prkg2tm1Pfe/tm1Pfe; MGI:2449704
involves: 129S1/Sv * 129X1/SvJ
Prkg2 knockout animals are dwarfs due to a defect in the endochondral ossification at the endochondral plate (5;10). The mice also had decreased digestive secretion in response to STa (an enterotoxin that normally stimulates cGMP accumulation and intestinal fluid secretion) (5).
|
| References |
1. Pfeifer, A., Ruth, P., Dostmann, W., Sausbier, M., Klatt, P., and Hofmann, F. (1999) Structure and Function of cGMP-Dependent Protein Kinases. Rev Physiol Biochem Pharmacol. 135, 105-149.
4. Wagner, C., Pfeifer, A., Ruth, P., Hofmann, F., and Kurtz, A. (1998) Role of cGMP-Kinase II in the Control of Renin Secretion and Renin Expression. J Clin Invest. 102, 1576-1582.
5. Pfeifer, A., Aszodi, A., Seidler, U., Ruth, P., Hofmann, F., and Fassler, R. (1996) Intestinal Secretory Defects and Dwarfism in Mice Lacking cGMP-Dependent Protein Kinase II. Science. 274, 2082-2086.
6. Werner, C., Raivich, G., Cowen, M., Strekalova, T., Sillaber, I., Buters, J. T., Spanagel, R., and Hofmann, F. (2004) Importance of NO/cGMP Signalling Via cGMP-Dependent Protein Kinase II for Controlling Emotionality and Neurobehavioural Effects of Alcohol. Eur J Neurosci. 20, 3498-3506.
7. Harada, N., Nagai, T., Shimokawa, O., Niikawa, N., and Matsumoto, N. (2002) A 4q21-q22 Deletion in a Girl with Severe Growth Retardation. Clin Genet. 61, 226-228.
8. Friedman, J. M., Baross, A., Delaney, A. D., Ally, A., Arbour, L., Armstrong, L., Asano, J., Bailey, D. K., Barber, S., Birch, P., Brown-John, M., Cao, M., Chan, S., Charest, D. L., Farnoud, N., Fernandes, N., Flibotte, S., Go, A., Gibson, W. T., Holt, R. A., Jones, S. J., Kennedy, G. C., Krzywinski, M., Langlois, S., Li, H. I., McGillivray, B. C., Nayar, T., Pugh, T. J., Rajcan-Separovic, E., Schein, J. E., Schnerch, A., Siddiqui, A., Van Allen, M. I., Wilson, G., Yong, S. L., Zahir, F., Eydoux, P., and Marra, M. A. (2006) Oligonucleotide Microarray Analysis of Genomic Imbalance in Children with Mental Retardation. Am J Hum Genet. 79, 500-513.
9. Bonnet, C., Andrieux, J., Beri-Dexheimer, M., Leheup, B., Boute, O., Manouvrier, S., Delobel, B., Copin, H., Receveur, A., Mathieu, M., Thiriez, G., Le Caignec, C., David, A., de Blois, M. C., Malan, V., Philippe, A., Cormier-Daire, V., Colleaux, L., Flori, E., Dollfus, H., Pelletier, V., Thauvin-Robinet, C., Masurel-Paulet, A., Faivre, L., Tardieu, M., Bahi-Buisson, N., Callier, P., Mugneret, F., Edery, P., Jonveaux, P., and Sanlaville, D. (2010) Microdeletion at Chromosome 4q21 Defines a New Emerging Syndrome with Marked Growth Restriction, Mental Retardation and Absent Or Severely Delayed Speech. J Med Genet. 47, 377-384.
10. Talts, J. F., Pfeifer, A., Hofmann, F., Hunziker, E. B., Zhou, X. H., Aszodi, A., and Fassler, R. (1998) Endochondral Ossification is Dependent on the Mechanical Properties of Cartilage Tissue and on Intracellular Signals in Chondrocytes. Ann N Y Acad Sci. 857, 74-85. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation