Incidental Mutation 'P0005:Prkg2'
ID7618
Institutional Source Beutler Lab
Gene Symbol Prkg2
Ensembl Gene ENSMUSG00000029334
Gene Nameprotein kinase, cGMP-dependent, type II
SynonymsPrkgr2, cGK-II
MMRRC Submission 038262-MU
Accession Numbers

NCBI RefSeq: NM_008926.4; MGI: 108173

Is this an essential gene? Probably non essential (E-score: 0.212) question?
Stock #P0005 (G1)
Quality Score
Status Validated
Chromosome5
Chromosomal Location98929773-99037351 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to C at 98969947 bp
ZygosityHeterozygous
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]
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 0.336 question?
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 80.5%
  • 10x: 66.1%
  • 20x: 49.6%
Validation Efficiency 95% (104/109)
MGI Phenotype Strain: 24494704
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
4933406M09Rik T A 1: 134,387,908 M15K probably benign Het
Atp13a1 T C 8: 69,803,747 V845A possibly damaging Het
C87499 A G 4: 88,627,950 L385P probably damaging Het
Casp6 T C 3: 129,912,143 V153A probably benign Het
Col6a1 A G 10: 76,717,329 probably benign Het
Dars2 A G 1: 161,053,939 probably null Het
Hmgcll1 T A 9: 76,074,759 M162K possibly damaging Het
Hydin A T 8: 110,494,289 probably null Het
Ift74 A G 4: 94,662,576 probably benign Het
Itpr1 A T 6: 108,381,257 I595F probably damaging Het
Mmp17 T C 5: 129,596,631 V258A probably benign Het
Nek6 T C 2: 38,569,737 probably null Het
Nomo1 A T 7: 46,037,557 probably null Het
Nudt3 A G 17: 27,596,715 probably benign Het
Ptp4a3 T A 15: 73,755,311 D72E possibly damaging Het
Rpgrip1l A T 8: 91,299,225 probably benign Het
Rrp9 G A 9: 106,481,177 R101H probably benign Het
Slc7a6os T C 8: 106,204,522 I161V probably benign Het
Tex15 T C 8: 33,570,868 F109L probably benign Het
Tns2 A G 15: 102,114,056 Q1188R probably damaging Het
Other mutations in Prkg2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00420:Prkg2 APN 5 99024541 missense probably benign 0.00
IGL01063:Prkg2 APN 5 98969936 critical splice donor site probably null
IGL02060:Prkg2 APN 5 99024515 missense probably benign 0.32
IGL02666:Prkg2 APN 5 98997519 splice site probably benign
IGL02992:Prkg2 APN 5 99024506 missense probably benign
IGL03040:Prkg2 APN 5 98973107 critical splice donor site probably null
devito UTSW 5 98966510 critical splice donor site probably null
R0044:Prkg2 UTSW 5 98973130 missense probably damaging 0.98
R0044:Prkg2 UTSW 5 98973130 missense probably damaging 0.98
R0115:Prkg2 UTSW 5 98994655 splice site probably null
R0403:Prkg2 UTSW 5 98994645 missense possibly damaging 0.95
R0452:Prkg2 UTSW 5 98997520 splice site probably benign
R0481:Prkg2 UTSW 5 98994655 splice site probably null
R1194:Prkg2 UTSW 5 98971926 missense probably benign 0.00
R1534:Prkg2 UTSW 5 98994561 missense probably damaging 1.00
R1861:Prkg2 UTSW 5 98947416 missense probably damaging 1.00
R2010:Prkg2 UTSW 5 99024805 missense probably benign
R2031:Prkg2 UTSW 5 99024451 missense possibly damaging 0.85
R2176:Prkg2 UTSW 5 98966509 splice site probably benign
R3607:Prkg2 UTSW 5 98947377 missense probably damaging 1.00
R3958:Prkg2 UTSW 5 98997495 missense possibly damaging 0.84
R3960:Prkg2 UTSW 5 98997495 missense possibly damaging 0.84
R4012:Prkg2 UTSW 5 98979815 missense possibly damaging 0.93
R4794:Prkg2 UTSW 5 98966633 missense probably damaging 1.00
R4840:Prkg2 UTSW 5 98981143 missense probably benign 0.03
R4867:Prkg2 UTSW 5 99024709 missense probably benign 0.21
R5182:Prkg2 UTSW 5 99024709 missense probably benign 0.21
R5226:Prkg2 UTSW 5 98976462 missense possibly damaging 0.92
R5274:Prkg2 UTSW 5 98969991 missense probably damaging 1.00
R5416:Prkg2 UTSW 5 98943467 missense probably benign 0.05
R5531:Prkg2 UTSW 5 98967734 missense probably damaging 1.00
R5619:Prkg2 UTSW 5 98988297 missense probably damaging 1.00
R6264:Prkg2 UTSW 5 98934364 missense probably benign 0.22
R6925:Prkg2 UTSW 5 98966510 critical splice donor site probably null
Z1088:Prkg2 UTSW 5 99024804 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
Posted On2012-10-05
Science WriterAnne Murray