Mutagenetix > Incidental Mutation

Incidental Mutation 'R4908:Slc12a3'

379202

Institutional Source

Beutler Lab

Gene Symbol

Slc12a3

Ensembl Gene

ENSMUSG00000031766

Gene Name

solute carrier family 12, member 3

Synonyms

TSC, NCC

MMRRC Submission

042510-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4908 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

95055829-95092842 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 95075216 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 737 (V737M)

Ref Sequence

ENSEMBL: ENSMUSP00000034218 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034218] [ENSMUST00000212134]

AlphaFold

P59158

Predicted Effect

possibly damaging
Transcript: ENSMUST00000034218
AA Change: V737M

PolyPhen 2 Score 0.756 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: V737M

Domain	Start	End	E-Value	Type
Pfam:AA_permease_N	43	114	1.5e-30	PFAM
Pfam:AA_permease	139	645	3.6e-145	PFAM
Pfam:SLC12	653	801	1.4e-53	PFAM
Pfam:SLC12	787	1001	2e-85	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212041

Predicted Effect

possibly damaging
Transcript: ENSMUST00000212134
AA Change: V737M

PolyPhen 2 Score 0.740 (Sensitivity: 0.85; Specificity: 0.92)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212632

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212915

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.2%
20x: 92.0%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit hypomagnesemia, hypocalciurua and abnormal renal distal convoluted tubule morphology, and show significantly reduced arterial blood pressure on a sodium-depleted diet. Mutant kidney cortical collecting ductsdisplay thiazide-sensitive NaCl absorption. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110059G10Rik	T	A	9: 122,778,008 (GRCm39)	I79L	probably benign	Het
Ablim2	C	T	5: 35,959,766 (GRCm39)	R73C	possibly damaging	Het
Acaa1a	G	A	9: 119,177,772 (GRCm39)	S218N	probably benign	Het
Acsm5	A	T	7: 119,137,314 (GRCm39)	I377F	probably damaging	Het
Ahnak2	T	C	12: 112,741,706 (GRCm39)	T789A	probably benign	Het
Ak9	A	T	10: 41,296,678 (GRCm39)	T1475S	unknown	Het
AU040320	A	T	4: 126,747,081 (GRCm39)	N1028Y	probably damaging	Het
Bahcc1	T	A	11: 120,178,580 (GRCm39)	S2380T	probably benign	Het
Cadps	A	G	14: 12,536,386 (GRCm38)	Y525H	probably damaging	Het
Casp8ap2	A	G	4: 32,639,905 (GRCm39)	T320A	possibly damaging	Het
Ccdc138	A	G	10: 58,380,817 (GRCm39)	N483D	possibly damaging	Het
Ccdc39	G	A	3: 33,893,242 (GRCm39)		probably null	Het
Cd300c2	T	C	11: 114,887,772 (GRCm39)	N210S	probably damaging	Het
Cd84	A	G	1: 171,700,432 (GRCm39)	D183G	probably damaging	Het
Cep95	C	T	11: 106,702,172 (GRCm39)	P390S	probably damaging	Het
Chd9	A	T	8: 91,741,877 (GRCm39)	H1622L	possibly damaging	Het
Cilp	C	A	9: 65,185,302 (GRCm39)	Q466K	probably benign	Het
Cinp	T	A	12: 110,850,487 (GRCm39)	T5S	probably damaging	Het
Clec4a2	T	C	6: 123,119,462 (GRCm39)	L238S	probably damaging	Het
Cntrob	T	C	11: 69,211,732 (GRCm39)	Y164C	probably damaging	Het
Col6a3	A	G	1: 90,735,246 (GRCm39)	L1408P	probably damaging	Het
Cul3	G	A	1: 80,258,632 (GRCm39)	S468L	possibly damaging	Het
Dnah11	T	A	12: 118,090,618 (GRCm39)	D1081V	probably benign	Het
Dnah2	C	A	11: 69,411,973 (GRCm39)	V263L	probably benign	Het
Efna3	C	G	3: 89,222,805 (GRCm39)	R185P	probably damaging	Het
F5	A	T	1: 164,039,389 (GRCm39)	I2000F	probably damaging	Het
Fancm	G	A	12: 65,141,645 (GRCm39)	G422E	probably benign	Het
Gcnt2	A	T	13: 41,014,210 (GRCm39)	D127V	probably damaging	Het
Gm21798	G	T	15: 64,689,618 (GRCm39)		probably benign	Het
Gramd1a	A	C	7: 30,838,292 (GRCm39)	S320R	probably benign	Het
Grn	T	C	11: 102,327,344 (GRCm39)		probably benign	Het
Helq	A	T	5: 100,910,507 (GRCm39)		probably null	Het
Herc2	A	G	7: 55,827,660 (GRCm39)	I2914V	probably benign	Het
Hnrnph1	T	C	11: 50,269,237 (GRCm39)	V27A	probably damaging	Het
Hs1bp3	G	T	12: 8,374,007 (GRCm39)	G182C	probably damaging	Het
Idnk	C	T	13: 58,311,267 (GRCm39)	P78L	probably benign	Het
Il10ra	T	C	9: 45,166,919 (GRCm39)	D544G	probably benign	Het
Inpp5e	T	C	2: 26,290,918 (GRCm39)	D383G	probably damaging	Het
Jak1	A	T	4: 101,036,911 (GRCm39)	V243D	probably damaging	Het
Kcnma1	A	T	14: 23,359,220 (GRCm39)	S1036T	probably damaging	Het
Kif26a	G	A	12: 112,123,776 (GRCm39)	C127Y	probably damaging	Het
Kif2c	T	C	4: 117,023,608 (GRCm39)	E368G	probably damaging	Het
Lasp1	T	A	11: 97,724,530 (GRCm39)		probably null	Het
Lcor	T	A	19: 41,572,601 (GRCm39)	V452D	probably benign	Het
Lrrtm1	C	G	6: 77,221,661 (GRCm39)	H373D	probably benign	Het
Matr3	T	A	18: 35,705,754 (GRCm39)	D226E	probably damaging	Het
Mmp17	G	A	5: 129,682,730 (GRCm39)	W456*	probably null	Het
Mpp4	T	C	1: 59,164,748 (GRCm39)	E463G	probably damaging	Het
Myh6	A	C	14: 55,194,419 (GRCm39)	F737V	probably damaging	Het
Nars2	T	A	7: 96,672,948 (GRCm39)	D271E	probably benign	Het
Nav2	A	G	7: 49,254,258 (GRCm39)	E2352G	probably damaging	Het
Nckap1	A	G	2: 80,353,718 (GRCm39)		probably null	Het
Nckap5	A	T	1: 125,955,324 (GRCm39)	S477R	probably damaging	Het
Nek11	T	G	9: 105,175,488 (GRCm39)	I319L	probably benign	Het
Neto2	A	G	8: 86,396,393 (GRCm39)	I84T	probably damaging	Het
Nlrp9a	A	T	7: 26,250,369 (GRCm39)	I45F	probably damaging	Het
Numa1	G	A	7: 101,662,012 (GRCm39)	R548H	probably damaging	Het
Or10a5	A	C	7: 106,635,364 (GRCm39)	M1L	probably benign	Het
Or14c39	A	C	7: 86,344,395 (GRCm39)	I244L	probably benign	Het
Or2ag1b	A	T	7: 106,288,740 (GRCm39)	L66H	probably damaging	Het
Or4c10	A	T	2: 89,760,923 (GRCm39)	M257L	probably benign	Het
Or4c100	T	A	2: 88,356,254 (GRCm39)	I109N	probably damaging	Het
Or4k36	T	A	2: 111,146,574 (GRCm39)	F250Y	probably benign	Het
Or7g25	A	G	9: 19,160,149 (GRCm39)	V182A	probably benign	Het
Or9m1	A	T	2: 87,733,533 (GRCm39)	N162K	probably damaging	Het
Pcdhb16	T	A	18: 37,612,894 (GRCm39)		probably null	Het
Pdcd10	T	C	3: 75,448,553 (GRCm39)	T4A	probably damaging	Het
Pgc	A	T	17: 48,039,819 (GRCm39)	Y71F	probably damaging	Het
Phlpp1	G	A	1: 106,317,481 (GRCm39)	G1234E	probably damaging	Het
Prr27	T	C	5: 87,990,888 (GRCm39)	F167L	probably benign	Het
Prrc2b	T	A	2: 32,116,330 (GRCm39)	S1421T	possibly damaging	Het
Pxmp2	A	G	5: 110,431,518 (GRCm39)	V75A	probably benign	Het
Pygl	A	T	12: 70,243,807 (GRCm39)	M545K	probably null	Het
Ranbp9	A	G	13: 43,574,733 (GRCm39)	Y412H	possibly damaging	Het
Rcc1	A	G	4: 132,065,064 (GRCm39)	V140A	probably damaging	Het
Reln	A	G	5: 22,184,718 (GRCm39)	V1599A	probably benign	Het
Rhebl1	A	T	15: 98,776,903 (GRCm39)	D122E	probably damaging	Het
Rock2	C	T	12: 17,009,492 (GRCm39)	L676F	probably benign	Het
Scn9a	A	T	2: 66,357,087 (GRCm39)	D1062E	probably benign	Het
Sec63	T	C	10: 42,681,186 (GRCm39)	I390T	probably damaging	Het
Slc10a6	T	C	5: 103,754,493 (GRCm39)	E346G	probably benign	Het
Slc12a8	T	C	16: 33,426,629 (GRCm39)		probably null	Het
Slc25a38	T	A	9: 119,949,354 (GRCm39)	I102N	probably damaging	Het
Spg7	T	A	8: 123,807,394 (GRCm39)	V390E	probably damaging	Het
Tbc1d20	T	C	2: 152,144,228 (GRCm39)	V75A	probably benign	Het
Tesk1	T	A	4: 43,445,555 (GRCm39)	C243*	probably null	Het
Ttk	T	A	9: 83,725,739 (GRCm39)	N220K	possibly damaging	Het
Ttll5	A	G	12: 85,965,948 (GRCm39)	E651G	probably benign	Het
Tubd1	T	C	11: 86,457,879 (GRCm39)	Y426H	probably damaging	Het
Uba6	T	C	5: 86,288,293 (GRCm39)		silent	Het
Ube2ql1	G	A	13: 69,852,289 (GRCm39)	R263W	probably damaging	Het
Vmn2r117	C	T	17: 23,678,812 (GRCm39)	G804D	probably damaging	Het
Vmn2r25	C	T	6: 123,805,406 (GRCm39)	E484K	probably benign	Het
Vmn2r4	T	A	3: 64,296,476 (GRCm39)	I770F	possibly damaging	Het
Vmn2r82	G	A	10: 79,214,589 (GRCm39)	V191M	probably benign	Het
Zbtb45	C	T	7: 12,742,037 (GRCm39)	V74M	probably damaging	Het
Zfp366	T	C	13: 99,370,609 (GRCm39)	V443A	possibly damaging	Het
Zfyve1	A	T	12: 83,598,345 (GRCm39)	C628S	probably damaging	Het
Zfyve26	A	T	12: 79,296,469 (GRCm39)		probably null	Het

Other mutations in Slc12a3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01823:Slc12a3	APN	8	95,083,724 (GRCm39)	missense	probably benign	0.00
IGL01947:Slc12a3	APN	8	95,092,447 (GRCm39)	critical splice acceptor site	probably null
IGL02151:Slc12a3	APN	8	95,075,220 (GRCm39)	missense	probably benign	0.26
IGL02440:Slc12a3	APN	8	95,058,310 (GRCm39)	missense	probably damaging	1.00
IGL03213:Slc12a3	APN	8	95,061,933 (GRCm39)	missense	possibly damaging	0.95
IGL03260:Slc12a3	APN	8	95,059,870 (GRCm39)	missense	probably damaging	1.00
IGL03306:Slc12a3	APN	8	95,078,386 (GRCm39)	missense	possibly damaging	0.72
IGL03329:Slc12a3	APN	8	95,092,519 (GRCm39)	missense	possibly damaging	0.67
avaricious	UTSW	8	95,057,100 (GRCm39)	missense	probably benign	0.01
Pugilist	UTSW	8	95,072,401 (GRCm39)	critical splice acceptor site	probably null
R0131:Slc12a3	UTSW	8	95,067,511 (GRCm39)	splice site	probably benign
R0189:Slc12a3	UTSW	8	95,082,986 (GRCm39)	missense	probably benign	0.30
R0330:Slc12a3	UTSW	8	95,072,974 (GRCm39)	missense	possibly damaging	0.75
R0569:Slc12a3	UTSW	8	95,057,153 (GRCm39)	critical splice donor site	probably null
R0715:Slc12a3	UTSW	8	95,056,061 (GRCm39)	missense	possibly damaging	0.75
R1248:Slc12a3	UTSW	8	95,059,905 (GRCm39)	missense	probably damaging	1.00
R1565:Slc12a3	UTSW	8	95,072,505 (GRCm39)	missense	possibly damaging	0.75
R2068:Slc12a3	UTSW	8	95,072,456 (GRCm39)	missense	probably damaging	1.00
R2108:Slc12a3	UTSW	8	95,067,158 (GRCm39)	missense	probably damaging	0.97
R2273:Slc12a3	UTSW	8	95,059,915 (GRCm39)	missense	possibly damaging	0.86
R2274:Slc12a3	UTSW	8	95,059,915 (GRCm39)	missense	possibly damaging	0.86
R2275:Slc12a3	UTSW	8	95,059,915 (GRCm39)	missense	possibly damaging	0.86
R2433:Slc12a3	UTSW	8	95,072,944 (GRCm39)	missense	probably benign	0.00
R3770:Slc12a3	UTSW	8	95,079,668 (GRCm39)	missense	probably benign
R4429:Slc12a3	UTSW	8	95,069,713 (GRCm39)	missense	probably damaging	1.00
R4431:Slc12a3	UTSW	8	95,069,713 (GRCm39)	missense	probably damaging	1.00
R4533:Slc12a3	UTSW	8	95,083,714 (GRCm39)	missense	probably null	0.02
R4627:Slc12a3	UTSW	8	95,056,012 (GRCm39)	missense	probably benign
R4856:Slc12a3	UTSW	8	95,078,438 (GRCm39)	critical splice donor site	probably null
R4886:Slc12a3	UTSW	8	95,078,438 (GRCm39)	critical splice donor site	probably null
R5054:Slc12a3	UTSW	8	95,072,979 (GRCm39)	missense	probably damaging	1.00
R5299:Slc12a3	UTSW	8	95,078,417 (GRCm39)	missense	probably damaging	1.00
R5451:Slc12a3	UTSW	8	95,083,655 (GRCm39)	missense	possibly damaging	0.61
R5590:Slc12a3	UTSW	8	95,072,416 (GRCm39)	missense	probably damaging	1.00
R5725:Slc12a3	UTSW	8	95,057,074 (GRCm39)	missense	probably benign	0.00
R6038:Slc12a3	UTSW	8	95,057,100 (GRCm39)	missense	probably benign	0.01
R6038:Slc12a3	UTSW	8	95,057,100 (GRCm39)	missense	probably benign	0.01
R6162:Slc12a3	UTSW	8	95,072,401 (GRCm39)	critical splice acceptor site	probably null
R6266:Slc12a3	UTSW	8	95,085,099 (GRCm39)	missense	possibly damaging	0.93
R6489:Slc12a3	UTSW	8	95,061,632 (GRCm39)	missense	possibly damaging	0.96
R6521:Slc12a3	UTSW	8	95,069,741 (GRCm39)	missense	possibly damaging	0.84
R6882:Slc12a3	UTSW	8	95,092,546 (GRCm39)	missense	possibly damaging	0.51
R7051:Slc12a3	UTSW	8	95,092,572 (GRCm39)	missense	probably damaging	1.00
R7510:Slc12a3	UTSW	8	95,092,477 (GRCm39)	missense	probably damaging	1.00
R7805:Slc12a3	UTSW	8	95,071,515 (GRCm39)	missense	probably damaging	1.00
R8152:Slc12a3	UTSW	8	95,057,012 (GRCm39)	missense	probably benign	0.00
R8412:Slc12a3	UTSW	8	95,060,695 (GRCm39)	missense	probably damaging	0.99
R8996:Slc12a3	UTSW	8	95,056,063 (GRCm39)	missense	probably benign
R9307:Slc12a3	UTSW	8	95,061,625 (GRCm39)	missense	probably benign	0.01
R9324:Slc12a3	UTSW	8	95,083,028 (GRCm39)	critical splice donor site	probably null
R9515:Slc12a3	UTSW	8	95,083,658 (GRCm39)	missense	possibly damaging	0.79
R9564:Slc12a3	UTSW	8	95,082,983 (GRCm39)	missense	probably benign	0.00
R9687:Slc12a3	UTSW	8	95,075,208 (GRCm39)	missense	possibly damaging	0.85

Predicted Primers

PCR Primer
(F):5'- GTATAGACAGAACCCTGAGCCC -3'
(R):5'- AAAGTTCCTGCGACCCCAAG -3'

Sequencing Primer
(F):5'- GAACCCTGAGCCCCTTGAAG -3'
(R):5'- ACCTCAGGGTCTATGAAGGTC -3'

Posted On

2016-04-15