Mutagenetix > Incidental Mutation

Incidental Mutation 'R2323:Wnk4'

244814

Institutional Source

Beutler Lab

Gene Symbol

Wnk4

Ensembl Gene

ENSMUSG00000035112

Gene Name

WNK lysine deficient protein kinase 4

Synonyms

2010002J11Rik, Prkwnk4

MMRRC Submission

040314-MU

Accession Numbers

Essential gene?

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

Stock #

R2323 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

101151393-101168235 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 101159307 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 575 (S575T)

Ref Sequence

ENSEMBL: ENSMUSP00000099397 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000103108] [ENSMUST00000139487] [ENSMUST00000147741] [ENSMUST00000170056]

AlphaFold

Q80UE6

Predicted Effect

probably damaging
Transcript: ENSMUST00000103108
AA Change: S575T

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000099397
Gene: ENSMUSG00000035112
AA Change: S575T

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: S138T

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000132123
Gene: ENSMUSG00000035112
AA Change: S138T

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

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.3%

Validation Efficiency

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: 34 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca2	G	T	2: 25,335,187 (GRCm39)	M2008I	probably benign	Het
Adgrv1	A	G	13: 81,743,298 (GRCm39)	S68P	probably damaging	Het
Albfm1	T	A	5: 90,732,711 (GRCm39)	Y507*	probably null	Het
Anks3	T	C	16: 4,768,634 (GRCm39)		probably null	Het
Asap2	T	C	12: 21,253,969 (GRCm39)	I160T	probably damaging	Het
Asb15	T	A	6: 24,556,600 (GRCm39)	F32I	probably benign	Het
Catip	A	T	1: 74,402,437 (GRCm39)	M103L	probably benign	Het
Cela2a	G	C	4: 141,553,390 (GRCm39)		probably benign	Het
Crebrf	T	C	17: 26,982,581 (GRCm39)		probably benign	Het
Dnah10	T	C	5: 124,819,064 (GRCm39)	M450T	probably damaging	Het
Dst	T	C	1: 34,267,518 (GRCm39)	S5165P	possibly damaging	Het
Esrp2	T	A	8: 106,860,934 (GRCm39)	D196V	probably benign	Het
Hmox2	A	T	16: 4,583,720 (GRCm39)	K263*	probably null	Het
Ints10	A	G	8: 69,271,997 (GRCm39)	H566R	probably benign	Het
Ints12	G	A	3: 132,815,126 (GRCm39)	M444I	possibly damaging	Het
Liph	A	G	16: 21,802,754 (GRCm39)	V105A	probably damaging	Het
Myo1e	T	A	9: 70,286,040 (GRCm39)	Y941*	probably null	Het
Myo7b	T	C	18: 32,104,398 (GRCm39)	E1450G	probably damaging	Het
Myt1	G	T	2: 181,448,350 (GRCm39)	A594S	probably damaging	Het
Npas3	T	A	12: 54,115,129 (GRCm39)	Y666N	probably damaging	Het
Npsr1	A	G	9: 24,211,732 (GRCm39)	K240E	probably damaging	Het
Or52h7	T	C	7: 104,213,826 (GRCm39)	F133L	probably benign	Het
Rtkn2	A	G	10: 67,837,764 (GRCm39)	I102M	probably damaging	Het
Rundc1	T	C	11: 101,316,101 (GRCm39)	F58L	probably damaging	Het
Snrpc	T	G	17: 28,066,948 (GRCm39)	M91R	unknown	Het
Tgfbr2	T	C	9: 115,939,212 (GRCm39)	K205R	possibly damaging	Het
Tmem181a	T	A	17: 6,346,061 (GRCm39)	L185H	probably damaging	Het
Tnfrsf21	C	A	17: 43,396,420 (GRCm39)	S568*	probably null	Het
Tulp1	C	T	17: 28,581,456 (GRCm39)	G239D	probably damaging	Het
Vmn1r234	T	C	17: 21,449,965 (GRCm39)	I293T	probably benign	Het
Vmn1r26	T	C	6: 57,985,842 (GRCm39)	K116E	probably damaging	Het
Vmn2r98	T	A	17: 19,286,081 (GRCm39)	I193K	probably benign	Het
Zfp558	A	T	9: 18,380,573 (GRCm39)		probably null	Het
Zscan18	T	C	7: 12,509,386 (GRCm39)		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
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
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'- AGAACGGGTTGCTGCTATC -3'
(R):5'- AGTCTCGCAATCAGCTGGTAG -3'

Sequencing Primer
(F):5'- AGCTTCGAAAAGCTAGGG -3'
(R):5'- CTCGCAATCAGCTGGTAGAGGAG -3'

Posted On

2014-10-30