Mutagenetix > Incidental Mutation

Incidental Mutation 'R0066:Wnk4'

41099

Institutional Source

Beutler Lab

Gene Symbol

Wnk4

Ensembl Gene

ENSMUSG00000035112

Gene Name

WNK lysine deficient protein kinase 4

Synonyms

2010002J11Rik, Prkwnk4

MMRRC Submission

038357-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.318) question?

Stock #

R0066 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

101151393-101168235 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 101156261 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 43 (D43V)

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: D480V

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

SMART Domains

Protein: ENSMUSP00000099397
Gene: ENSMUSG00000035112
AA Change: D480V

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: D43V

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

SMART Domains

Protein: ENSMUSP00000132123
Gene: ENSMUSG00000035112
AA Change: D43V

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

0.7233

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 93.0%

Validation Efficiency

100% (107/107)

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: 104 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810064F22Rik	A	G	9: 22,119,177 (GRCm39)		noncoding transcript	Het
5530400C23Rik	A	T	6: 133,269,287 (GRCm39)		probably benign	Het
Aco2	T	C	15: 81,787,666 (GRCm39)		probably benign	Het
Arap3	A	T	18: 38,129,760 (GRCm39)	S134T	probably benign	Het
Arsa	T	A	15: 89,358,539 (GRCm39)	M288L	possibly damaging	Het
Atg2b	A	T	12: 105,614,708 (GRCm39)	D1074E	probably benign	Het
Baiap2l1	A	T	5: 144,221,372 (GRCm39)	I174N	probably damaging	Het
Bpifb9a	A	T	2: 154,108,761 (GRCm39)	N421Y	possibly damaging	Het
Btn2a2	T	A	13: 23,662,655 (GRCm39)	I432L	probably benign	Het
Ccdc150	A	G	1: 54,395,850 (GRCm39)	I778V	probably benign	Het
Cd200r2	G	A	16: 44,730,037 (GRCm39)	V194I	possibly damaging	Het
Cep350	A	C	1: 155,786,964 (GRCm39)	L1421R	probably damaging	Het
Col24a1	G	A	3: 145,250,899 (GRCm39)	A1633T	probably damaging	Het
Col6a6	A	T	9: 105,579,412 (GRCm39)	C1938S	probably damaging	Het
Cspg4	A	T	9: 56,795,418 (GRCm39)	D1051V	probably damaging	Het
Cstf1	T	A	2: 172,214,976 (GRCm39)	N32K	probably benign	Het
Ctrb1	G	A	8: 112,413,269 (GRCm39)	R248*	probably null	Het
Cyp2d11	T	A	15: 82,275,958 (GRCm39)	M208L	probably benign	Het
Dbt	A	G	3: 116,337,478 (GRCm39)	Q334R	probably benign	Het
Dcaf12	A	G	4: 41,298,338 (GRCm39)	V270A	probably damaging	Het
Dis3l	T	A	9: 64,226,447 (GRCm39)	N361I	probably benign	Het
Dnah10	A	T	5: 124,840,140 (GRCm39)	D1315V	probably benign	Het
Dnah11	A	G	12: 118,090,621 (GRCm39)	F1080S	probably benign	Het
Dnm3	A	G	1: 162,234,930 (GRCm39)	V70A	probably damaging	Het
Dpy19l1	A	C	9: 24,325,705 (GRCm39)	M700R	possibly damaging	Het
Dpy19l2	G	A	9: 24,557,679 (GRCm39)		probably benign	Het
Dst	C	A	1: 34,228,634 (GRCm39)	H2254N	possibly damaging	Het
Epm2aip1	A	G	9: 111,101,531 (GRCm39)	N168S	probably benign	Het
Fchsd2	A	G	7: 100,927,631 (GRCm39)	Y691C	possibly damaging	Het
Fndc8	A	T	11: 82,788,398 (GRCm39)	D76V	probably benign	Het
Frmd4a	T	C	2: 4,477,963 (GRCm39)	L48P	probably damaging	Het
Gimap6	T	A	6: 48,679,404 (GRCm39)	I211F	probably damaging	Het
Gm15130	A	G	2: 110,969,284 (GRCm39)		probably benign	Het
Gm43302	T	A	5: 105,438,766 (GRCm39)	I41F	probably damaging	Het
Gm5698	C	T	1: 31,016,614 (GRCm39)	V146I	probably benign	Het
Gpatch1	G	A	7: 34,986,652 (GRCm39)	S768L	probably damaging	Het
Grb14	T	G	2: 64,768,836 (GRCm39)		probably null	Het
Hnrnpd	T	C	5: 100,112,560 (GRCm39)	E222G	probably damaging	Het
Il4ra	C	T	7: 125,175,403 (GRCm39)	P537L	possibly damaging	Het
Kalrn	T	C	16: 34,024,327 (GRCm39)	D610G	probably damaging	Het
Kcnh4	T	C	11: 100,648,626 (GRCm39)	H26R	probably benign	Het
Kctd2	T	G	11: 115,320,343 (GRCm39)		probably benign	Het
Khdrbs3	T	A	15: 68,866,886 (GRCm39)		probably benign	Het
Macf1	G	A	4: 123,325,943 (GRCm39)	Q3066*	probably null	Het
Mfn2	G	A	4: 147,969,902 (GRCm39)		probably benign	Het
Mmab	T	C	5: 114,574,526 (GRCm39)		probably benign	Het
Mrc1	T	C	2: 14,266,011 (GRCm39)	S310P	probably benign	Het
Mrps21	T	C	3: 95,770,197 (GRCm39)	Y44C	probably null	Het
Myh10	T	A	11: 68,590,317 (GRCm39)	F121Y	probably damaging	Het
Myo1f	A	G	17: 33,820,677 (GRCm39)	D840G	probably damaging	Het
Neb	T	A	2: 52,196,542 (GRCm39)	D553V	probably damaging	Het
Nol6	G	T	4: 41,119,572 (GRCm39)		probably benign	Het
Npr2	G	T	4: 43,632,329 (GRCm39)	V49L	probably benign	Het
Ntsr2	T	C	12: 16,704,120 (GRCm39)	I207T	probably benign	Het
Nwd1	T	A	8: 73,438,484 (GRCm39)	S1552T	probably benign	Het
Oas3	T	A	5: 120,896,940 (GRCm39)	I894F	probably damaging	Het
Oprd1	A	G	4: 131,841,299 (GRCm39)	F220L	probably benign	Het
Or11j4	T	A	14: 50,630,659 (GRCm39)	F149I	probably benign	Het
Or2aj4	T	A	16: 19,384,799 (GRCm39)	Y278F	probably damaging	Het
Or2r2	A	T	6: 42,463,869 (GRCm39)	M86K	probably benign	Het
Or8b57	T	C	9: 40,003,983 (GRCm39)	N93S	possibly damaging	Het
Pkd1l3	G	T	8: 110,347,103 (GRCm39)	G159C	unknown	Het
Plcb4	T	C	2: 135,803,689 (GRCm39)	S521P	probably benign	Het
Plcl1	A	T	1: 55,752,634 (GRCm39)	I993F	probably damaging	Het
Plcxd1	T	A	5: 110,249,368 (GRCm39)	V65E	probably damaging	Het
Plekha7	T	C	7: 115,756,743 (GRCm39)	S640G	probably damaging	Het
Ptprn2	A	C	12: 117,240,222 (GRCm39)	N993T	probably benign	Het
Rabepk	T	C	2: 34,685,318 (GRCm39)	D26G	possibly damaging	Het
Reck	A	G	4: 43,930,936 (GRCm39)	N646D	probably damaging	Het
Rfx2	A	T	17: 57,093,736 (GRCm39)		probably benign	Het
Ripk2	G	A	4: 16,123,868 (GRCm39)	Q436*	probably null	Het
Ryr1	C	T	7: 28,704,992 (GRCm39)		probably benign	Het
Sema6b	A	G	17: 56,435,271 (GRCm39)	V324A	possibly damaging	Het
Sik2	C	A	9: 50,909,833 (GRCm39)	M73I	probably benign	Het
Slc39a6	T	C	18: 24,732,326 (GRCm39)	K321E	probably damaging	Het
Slc7a4	C	A	16: 17,391,875 (GRCm39)	V520F	probably benign	Het
Slitrk6	A	T	14: 110,987,364 (GRCm39)	L781H	probably damaging	Het
Spink14	T	C	18: 44,161,830 (GRCm39)	V2A	probably benign	Het
Sptan1	C	A	2: 29,893,679 (GRCm39)		probably benign	Het
Stab1	C	T	14: 30,879,027 (GRCm39)		probably benign	Het
Tbc1d17	C	T	7: 44,493,495 (GRCm39)		probably benign	Het
Tbcd	T	A	11: 121,394,590 (GRCm39)	L49*	probably null	Het
Tmco6	A	G	18: 36,875,160 (GRCm39)	T477A	probably benign	Het
Tmem208	C	T	8: 106,054,857 (GRCm39)	A53V	probably benign	Het
Tpp2	A	G	1: 44,020,908 (GRCm39)	T837A	possibly damaging	Het
Tulp4	A	T	17: 6,252,008 (GRCm39)	N60I	probably damaging	Het
Ubqlnl	A	T	7: 103,798,145 (GRCm39)	W451R	probably damaging	Het
Usp53	G	T	3: 122,746,956 (GRCm39)	C363*	probably null	Het
Usp7	A	T	16: 8,509,282 (GRCm39)	H1017Q	probably benign	Het
Utp4	A	G	8: 107,649,530 (GRCm39)	T660A	possibly damaging	Het
Vmn1r194	A	T	13: 22,428,641 (GRCm39)	Y86F	probably benign	Het
Vmn1r195	A	T	13: 22,463,409 (GRCm39)	H293L	possibly damaging	Het
Vmn1r231	T	C	17: 21,109,998 (GRCm39)	R306G	probably benign	Het
Vmn2r63	T	C	7: 42,576,514 (GRCm39)		probably benign	Het
Vmn2r77	T	C	7: 86,449,964 (GRCm39)	V70A	probably benign	Het
Vmn2r85	T	C	10: 130,261,770 (GRCm39)	D189G	probably damaging	Het
Vps8	A	G	16: 21,296,273 (GRCm39)	E515G	possibly damaging	Het
Wdr18	C	A	10: 79,796,937 (GRCm39)	Y104*	probably null	Het
Xab2	A	T	8: 3,663,880 (GRCm39)	N346K	probably damaging	Het
Xirp2	T	C	2: 67,342,484 (GRCm39)	V1575A	possibly damaging	Het
Zdhhc12	C	T	2: 29,982,547 (GRCm39)	R50H	probably damaging	Het
Zdhhc8	A	G	16: 18,043,064 (GRCm39)	S379P	probably benign	Het
Zfp458	G	A	13: 67,407,673 (GRCm39)	Q58*	probably null	Het
Zfp747	A	T	7: 126,973,772 (GRCm39)	S133T	probably benign	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
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
R6274:Wnk4	UTSW	11	101,156,257 (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'- TCATTGAAGGCTGCATCCGCAC -3'
(R):5'- CCGTCCTGGAACTGATGATGCTAAG -3'

Sequencing Primer
(F):5'- TGCATCCGCACGGATAAG -3'
(R):5'- CATAGACCggggggggg -3'

Posted On

2013-05-23