Incidental Mutation 'R6274:Wnk4'
| ID |
507540 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Wnk4
|
| Ensembl Gene |
ENSMUSG00000035112 |
| Gene Name |
WNK lysine deficient protein kinase 4 |
| Synonyms |
2010002J11Rik, Prkwnk4 |
| MMRRC Submission |
044444-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.318)
|
| Stock # |
R6274 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
101151393-101168235 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 101156257 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Tryptophan
at position 42
(R42W)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000132123
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000103108]
[ENSMUST00000139487]
[ENSMUST00000147741]
[ENSMUST00000170056]
|
| AlphaFold |
Q80UE6 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000103108
AA Change: R479W
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000099397
Gene: ENSMUSG00000035112
AA Change: R479W
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
31 |
45 |
N/A |
INTRINSIC |
|
low complexity region
|
52 |
64 |
N/A |
INTRINSIC |
|
low complexity region
|
76 |
92 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
105 |
N/A |
INTRINSIC |
|
low complexity region
|
126 |
155 |
N/A |
INTRINSIC |
|
Pfam:Pkinase_Tyr
|
171 |
427 |
4.7e-42 |
PFAM |
|
Pfam:Pkinase
|
171 |
429 |
9e-55 |
PFAM |
|
Pfam:OSR1_C
|
450 |
486 |
3e-18 |
PFAM |
|
low complexity region
|
503 |
513 |
N/A |
INTRINSIC |
|
low complexity region
|
516 |
530 |
N/A |
INTRINSIC |
|
low complexity region
|
544 |
560 |
N/A |
INTRINSIC |
|
low complexity region
|
627 |
638 |
N/A |
INTRINSIC |
|
low complexity region
|
660 |
678 |
N/A |
INTRINSIC |
|
low complexity region
|
757 |
778 |
N/A |
INTRINSIC |
|
low complexity region
|
793 |
808 |
N/A |
INTRINSIC |
|
low complexity region
|
841 |
877 |
N/A |
INTRINSIC |
|
low complexity region
|
882 |
915 |
N/A |
INTRINSIC |
|
low complexity region
|
921 |
951 |
N/A |
INTRINSIC |
|
low complexity region
|
1014 |
1033 |
N/A |
INTRINSIC |
|
low complexity region
|
1093 |
1112 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000139487
|
| SMART Domains |
Protein: ENSMUSP00000129666
Gene: ENSMUSG00000035112
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
31 |
45 |
N/A |
INTRINSIC |
|
low complexity region
|
52 |
64 |
N/A |
INTRINSIC |
|
low complexity region
|
76 |
92 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
105 |
N/A |
INTRINSIC |
|
low complexity region
|
126 |
155 |
N/A |
INTRINSIC |
|
Pfam:Pkinase_Tyr
|
171 |
242 |
4e-8 |
PFAM |
|
Pfam:Pkinase
|
171 |
252 |
1.9e-10 |
PFAM |
|
low complexity region
|
269 |
283 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000147741
|
| SMART Domains |
Protein: ENSMUSP00000131298
Gene: ENSMUSG00000035112
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
31 |
45 |
N/A |
INTRINSIC |
|
low complexity region
|
52 |
64 |
N/A |
INTRINSIC |
|
low complexity region
|
76 |
92 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
105 |
N/A |
INTRINSIC |
|
low complexity region
|
126 |
155 |
N/A |
INTRINSIC |
|
Pfam:Pkinase
|
171 |
394 |
9.3e-50 |
PFAM |
|
Pfam:Pkinase_Tyr
|
171 |
399 |
3.7e-38 |
PFAM |
|
low complexity region
|
401 |
413 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000156205
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000170056
AA Change: R42W
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000132123
Gene: ENSMUSG00000035112
AA Change: R42W
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:OSR1_C
|
13 |
49 |
8.6e-20 |
PFAM |
|
low complexity region
|
66 |
76 |
N/A |
INTRINSIC |
|
low complexity region
|
79 |
93 |
N/A |
INTRINSIC |
|
low complexity region
|
107 |
123 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.2548 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 97.9%
- 20x: 94.1%
|
| Validation Efficiency |
100% (56/56) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]
PHENOTYPE: Mice homozygous for a null allele display increased Na+, K+ and Cl- urinary excretion, alkalosis and decreased plasma Cl-, K+, Mg2+ and renin levels. Mice homozygous for a point mutation exhibit acidosis, hypertension, increased circulating potassium levels and decreased potassium excretion. [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 |
|---|
| Ank3 |
G |
A |
10: 69,838,395 (GRCm39) |
R1566K |
possibly damaging |
Het |
| Ano1 |
A |
T |
7: 144,172,600 (GRCm39) |
S528T |
probably benign |
Het |
| Araf |
G |
T |
X: 20,726,339 (GRCm39) |
R601L |
probably damaging |
Homo |
| Bcl2l10 |
T |
C |
9: 75,258,354 (GRCm39) |
I172T |
possibly damaging |
Het |
| Bpifb3 |
A |
T |
2: 153,771,243 (GRCm39) |
N385I |
possibly damaging |
Het |
| Bsnd |
A |
G |
4: 106,343,832 (GRCm39) |
V158A |
probably damaging |
Het |
| Cacna1s |
A |
G |
1: 136,016,783 (GRCm39) |
N481S |
probably benign |
Het |
| Cdk5rap1 |
A |
G |
2: 154,210,161 (GRCm39) |
V138A |
probably damaging |
Het |
| Cep290 |
A |
G |
10: 100,366,069 (GRCm39) |
E1099G |
probably damaging |
Het |
| Cers1 |
T |
A |
8: 70,783,727 (GRCm39) |
L225Q |
probably damaging |
Het |
| Cfb |
T |
C |
17: 35,081,069 (GRCm39) |
Q7R |
probably benign |
Het |
| Clk4 |
A |
G |
11: 51,162,748 (GRCm39) |
S98G |
possibly damaging |
Het |
| Clock |
A |
G |
5: 76,385,000 (GRCm39) |
S406P |
probably benign |
Het |
| Csmd3 |
T |
C |
15: 47,484,833 (GRCm39) |
I3178V |
probably benign |
Het |
| Dock10 |
A |
G |
1: 80,516,540 (GRCm39) |
S1397P |
probably damaging |
Het |
| Fer1l4 |
A |
G |
2: 155,871,188 (GRCm39) |
L1421P |
probably damaging |
Het |
| Fetub |
C |
T |
16: 22,751,081 (GRCm39) |
R143C |
probably damaging |
Het |
| Greb1 |
G |
T |
12: 16,785,152 (GRCm39) |
T91K |
probably damaging |
Het |
| Grid2ip |
G |
A |
5: 143,366,184 (GRCm39) |
S379N |
probably damaging |
Het |
| Gucy1b2 |
A |
T |
14: 62,653,388 (GRCm39) |
C336S |
probably damaging |
Het |
| Hdac1 |
A |
G |
4: 129,412,902 (GRCm39) |
C261R |
probably damaging |
Het |
| Htt |
T |
C |
5: 35,009,431 (GRCm39) |
S1471P |
possibly damaging |
Het |
| Ice1 |
A |
G |
13: 70,742,958 (GRCm39) |
V2134A |
probably damaging |
Het |
| Ikzf1 |
C |
T |
11: 11,718,961 (GRCm39) |
Q310* |
probably null |
Het |
| Il3ra |
G |
A |
14: 14,350,180 (GRCm38) |
V112I |
probably benign |
Het |
| Kif21b |
A |
G |
1: 136,077,156 (GRCm39) |
I393V |
possibly damaging |
Het |
| Krt74 |
T |
C |
15: 101,671,872 (GRCm39) |
|
noncoding transcript |
Het |
| Krtap29-1 |
T |
C |
11: 99,869,809 (GRCm39) |
N24S |
probably null |
Het |
| Mmut |
T |
C |
17: 41,267,136 (GRCm39) |
V570A |
probably benign |
Het |
| Myh7 |
T |
C |
14: 55,216,943 (GRCm39) |
D1138G |
probably damaging |
Het |
| Nktr |
T |
C |
9: 121,560,631 (GRCm39) |
I125T |
probably damaging |
Het |
| Nlrp2 |
A |
T |
7: 5,320,554 (GRCm39) |
L861Q |
probably damaging |
Het |
| Notch3 |
C |
A |
17: 32,366,264 (GRCm39) |
R990L |
probably benign |
Het |
| Nrap |
T |
C |
19: 56,350,153 (GRCm39) |
D655G |
probably benign |
Het |
| Or10ak8 |
A |
T |
4: 118,774,427 (GRCm39) |
V79E |
probably benign |
Het |
| Or5b99 |
G |
A |
19: 12,977,234 (GRCm39) |
V295I |
probably damaging |
Het |
| Osbpl11 |
T |
A |
16: 33,047,426 (GRCm39) |
I463N |
probably damaging |
Het |
| Pcsk6 |
A |
T |
7: 65,683,592 (GRCm39) |
R749W |
probably damaging |
Het |
| Plaat5 |
C |
T |
19: 7,614,831 (GRCm39) |
T231I |
probably damaging |
Het |
| Plxnb1 |
T |
C |
9: 108,941,209 (GRCm39) |
|
probably null |
Het |
| Polr1a |
T |
A |
6: 71,931,874 (GRCm39) |
|
probably null |
Het |
| Ppm1g |
T |
C |
5: 31,363,750 (GRCm39) |
I153V |
probably damaging |
Het |
| Ppp1r12a |
T |
C |
10: 108,096,751 (GRCm39) |
S191P |
probably benign |
Het |
| Prodh |
T |
C |
16: 17,898,922 (GRCm39) |
K178E |
possibly damaging |
Het |
| Rilpl2 |
A |
G |
5: 124,607,911 (GRCm39) |
V103A |
possibly damaging |
Het |
| Sap18b |
C |
T |
8: 96,552,169 (GRCm39) |
H60Y |
probably benign |
Het |
| Sclt1 |
A |
G |
3: 41,583,951 (GRCm39) |
|
probably null |
Het |
| Serpinb1a |
G |
T |
13: 33,026,849 (GRCm39) |
H364Q |
probably damaging |
Het |
| Sez6l |
G |
A |
5: 112,623,231 (GRCm39) |
Q107* |
probably null |
Het |
| Sipa1l2 |
C |
T |
8: 126,196,611 (GRCm39) |
V708I |
probably damaging |
Het |
| Tbc1d2 |
C |
T |
4: 46,629,912 (GRCm39) |
G252R |
probably benign |
Het |
| Uaca |
T |
A |
9: 60,757,573 (GRCm39) |
|
probably null |
Het |
| Uqcrc1 |
C |
A |
9: 108,771,224 (GRCm39) |
H95N |
probably damaging |
Het |
| Usp9y |
C |
T |
Y: 1,316,735 (GRCm39) |
R1938H |
probably damaging |
Homo |
| Zfp326 |
T |
A |
5: 106,053,846 (GRCm39) |
L242Q |
probably damaging |
Het |
|
| Other mutations in Wnk4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00231:Wnk4
|
APN |
11 |
101,159,574 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
IGL00535:Wnk4
|
APN |
11 |
101,155,175 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01401:Wnk4
|
APN |
11 |
101,167,509 (GRCm39) |
splice site |
probably benign |
|
|
IGL01931:Wnk4
|
APN |
11 |
101,159,310 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
IGL01977:Wnk4
|
APN |
11 |
101,156,240 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02165:Wnk4
|
APN |
11 |
101,166,117 (GRCm39) |
unclassified |
probably benign |
|
|
IGL02197:Wnk4
|
APN |
11 |
101,154,783 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02457:Wnk4
|
APN |
11 |
101,160,389 (GRCm39) |
splice site |
probably benign |
|
|
IGL02963:Wnk4
|
APN |
11 |
101,167,039 (GRCm39) |
unclassified |
probably benign |
|
|
ashamed
|
UTSW |
11 |
101,156,257 (GRCm39) |
missense |
probably damaging |
1.00 |
|
blushing
|
UTSW |
11 |
101,156,203 (GRCm39) |
missense |
probably damaging |
0.96 |
|
Caught_dead
|
UTSW |
11 |
101,155,156 (GRCm39) |
missense |
probably damaging |
1.00 |
|
lowered
|
UTSW |
11 |
101,159,318 (GRCm39) |
critical splice donor site |
probably null |
|
|
mortification
|
UTSW |
11 |
101,154,720 (GRCm39) |
makesense |
probably null |
|
|
shame
|
UTSW |
11 |
101,153,682 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0066:Wnk4
|
UTSW |
11 |
101,156,261 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0317:Wnk4
|
UTSW |
11 |
101,159,630 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0628:Wnk4
|
UTSW |
11 |
101,165,849 (GRCm39) |
missense |
probably benign |
0.10 |
|
R0630:Wnk4
|
UTSW |
11 |
101,156,212 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0710:Wnk4
|
UTSW |
11 |
101,164,932 (GRCm39) |
missense |
probably benign |
0.22 |
|
R1290:Wnk4
|
UTSW |
11 |
101,167,166 (GRCm39) |
unclassified |
probably benign |
|
|
R1482:Wnk4
|
UTSW |
11 |
101,160,462 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1775:Wnk4
|
UTSW |
11 |
101,167,166 (GRCm39) |
unclassified |
probably benign |
|
|
R2005:Wnk4
|
UTSW |
11 |
101,154,716 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2229:Wnk4
|
UTSW |
11 |
101,166,467 (GRCm39) |
unclassified |
probably benign |
|
|
R2258:Wnk4
|
UTSW |
11 |
101,165,861 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2323:Wnk4
|
UTSW |
11 |
101,159,307 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R3081:Wnk4
|
UTSW |
11 |
101,167,717 (GRCm39) |
splice site |
probably benign |
|
|
R3763:Wnk4
|
UTSW |
11 |
101,160,114 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4196:Wnk4
|
UTSW |
11 |
101,160,457 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4447:Wnk4
|
UTSW |
11 |
101,159,277 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R4614:Wnk4
|
UTSW |
11 |
101,164,937 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4751:Wnk4
|
UTSW |
11 |
101,167,188 (GRCm39) |
unclassified |
probably benign |
|
|
R4948:Wnk4
|
UTSW |
11 |
101,159,107 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5067:Wnk4
|
UTSW |
11 |
101,153,682 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5073:Wnk4
|
UTSW |
11 |
101,152,014 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5107:Wnk4
|
UTSW |
11 |
101,166,364 (GRCm39) |
unclassified |
probably benign |
|
|
R5181:Wnk4
|
UTSW |
11 |
101,156,203 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R5205:Wnk4
|
UTSW |
11 |
101,155,964 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R5252:Wnk4
|
UTSW |
11 |
101,159,574 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
R5273:Wnk4
|
UTSW |
11 |
101,154,695 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5293:Wnk4
|
UTSW |
11 |
101,166,023 (GRCm39) |
unclassified |
probably benign |
|
|
R5609:Wnk4
|
UTSW |
11 |
101,166,462 (GRCm39) |
unclassified |
probably benign |
|
|
R5915:Wnk4
|
UTSW |
11 |
101,154,720 (GRCm39) |
makesense |
probably null |
|
|
R5931:Wnk4
|
UTSW |
11 |
101,152,047 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6126:Wnk4
|
UTSW |
11 |
101,167,174 (GRCm39) |
unclassified |
probably benign |
|
|
R6164:Wnk4
|
UTSW |
11 |
101,165,894 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R6191:Wnk4
|
UTSW |
11 |
101,155,156 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6267:Wnk4
|
UTSW |
11 |
101,164,824 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6296:Wnk4
|
UTSW |
11 |
101,164,824 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7132:Wnk4
|
UTSW |
11 |
101,152,026 (GRCm39) |
missense |
probably benign |
0.22 |
|
R7251:Wnk4
|
UTSW |
11 |
101,155,979 (GRCm39) |
missense |
possibly damaging |
0.70 |
|
R7352:Wnk4
|
UTSW |
11 |
101,155,244 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7404:Wnk4
|
UTSW |
11 |
101,159,318 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7624:Wnk4
|
UTSW |
11 |
101,155,180 (GRCm39) |
nonsense |
probably null |
|
|
R7634:Wnk4
|
UTSW |
11 |
101,153,721 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7780:Wnk4
|
UTSW |
11 |
101,160,403 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R8006:Wnk4
|
UTSW |
11 |
101,159,182 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8046:Wnk4
|
UTSW |
11 |
101,164,918 (GRCm39) |
missense |
probably benign |
0.20 |
|
R8143:Wnk4
|
UTSW |
11 |
101,153,625 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8458:Wnk4
|
UTSW |
11 |
101,166,147 (GRCm39) |
nonsense |
probably null |
|
|
R8735:Wnk4
|
UTSW |
11 |
101,167,092 (GRCm39) |
missense |
unknown |
|
|
R9025:Wnk4
|
UTSW |
11 |
101,153,641 (GRCm39) |
nonsense |
probably null |
|
|
R9206:Wnk4
|
UTSW |
11 |
101,164,882 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9295:Wnk4
|
UTSW |
11 |
101,160,078 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9610:Wnk4
|
UTSW |
11 |
101,159,250 (GRCm39) |
nonsense |
probably null |
|
|
R9611:Wnk4
|
UTSW |
11 |
101,159,250 (GRCm39) |
nonsense |
probably null |
|
|
R9674:Wnk4
|
UTSW |
11 |
101,166,874 (GRCm39) |
missense |
unknown |
|
|
| Predicted Primers |
PCR Primer
(F):5'- AGGTTCACCATCCAGGATCTCC -3'
(R):5'- AAAAGAACCCTGGTGTGCG -3'
Sequencing Primer
(F):5'- AGGATCTCCTGGCCCATG -3'
(R):5'- TGTGCGCAGACGGATTAG -3'
|
| Posted On |
2018-03-15 |
Incidental Mutation