Mutagenetix > Incidental Mutation

Incidental Mutation 'R9515:Slc12a3'

718483

Institutional Source

Beutler Lab

Gene Symbol

Slc12a3

Ensembl Gene

ENSMUSG00000031766

Gene Name

solute carrier family 12, member 3

Synonyms

TSC, NCC

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R9515 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

95055829-95092842 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 95083658 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Lysine at position 895 (M895K)

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: M895K

PolyPhen 2 Score 0.788 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: M895K

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

possibly damaging
Transcript: ENSMUST00000212134
AA Change: M895K

PolyPhen 2 Score 0.788 (Sensitivity: 0.85; Specificity: 0.93)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

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: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2200002D01Rik	CCTTCTCCTTCTTCTCCTTCTTCTCCTTCTTCTCCATCTTCTCCTTCTTC	CCTTCTCCTTCTTCTCCTTCTTCTCCATCTTCTCCTTCTTC	7: 28,947,048 (GRCm39)		probably benign	Het
Aamdc	A	G	7: 97,224,808 (GRCm39)	V18A	probably benign	Het
Adam12	T	A	7: 133,509,373 (GRCm39)	I796F	probably benign	Het
Adcy7	T	A	8: 89,037,646 (GRCm39)	V238E	possibly damaging	Het
Adgrv1	G	A	13: 81,691,497 (GRCm39)	H1697Y	probably damaging	Het
Adrb1	A	G	19: 56,711,825 (GRCm39)	D341G	probably benign	Het
Akap13	T	C	7: 75,354,275 (GRCm39)	Y80H	probably benign	Het
Akap9	C	T	5: 4,105,709 (GRCm39)	L2927F	probably damaging	Het
Alox8	T	A	11: 69,075,950 (GRCm39)	D667V	probably damaging	Het
Arhgap30	A	G	1: 171,236,002 (GRCm39)	E792G	probably benign	Het
Arhgef16	A	G	4: 154,365,432 (GRCm39)	V561A	possibly damaging	Het
Bcap29	A	T	12: 31,676,756 (GRCm39)	Y105N	probably damaging	Het
Best2	T	A	8: 85,740,147 (GRCm39)	T6S		Het
Bfsp2	C	A	9: 103,357,251 (GRCm39)	V59L	possibly damaging	Het
Brd3	T	A	2: 27,349,815 (GRCm39)	D246V		Het
Btnl1	T	A	17: 34,600,118 (GRCm39)	V207E	probably benign	Het
Ccdc122	T	A	14: 77,329,408 (GRCm39)	Y154N		Het
Cfap43	A	G	19: 47,773,814 (GRCm39)	Y656H	probably damaging	Het
Clca3a2	A	T	3: 144,508,808 (GRCm39)	Y670*	probably null	Het
Coprs	T	C	8: 13,935,081 (GRCm39)	Y158C	probably damaging	Het
Desi2	T	G	1: 178,084,170 (GRCm39)	M106R	unknown	Het
Dnaaf3	T	C	7: 4,531,100 (GRCm39)	E111G	probably damaging	Het
Epha10	T	A	4: 124,775,704 (GRCm39)	F13I	probably benign	Het
Fam193a	T	A	5: 34,615,371 (GRCm39)	F813L	possibly damaging	Het
Fbn1	C	A	2: 125,207,551 (GRCm39)	A981S	probably benign	Het
Gga2	T	A	7: 121,611,448 (GRCm39)	T37S	probably damaging	Het
Glra3	T	A	8: 56,578,299 (GRCm39)	F452Y	probably damaging	Het
Gm10338	T	A	14: 19,280,438 (GRCm39)	N96I	probably damaging	Het
Gpd2	A	T	2: 57,195,866 (GRCm39)	E149V	possibly damaging	Het
Gpr137c	T	G	14: 45,516,229 (GRCm39)	L321*	probably null	Het
Gsdmc2	T	C	15: 63,702,678 (GRCm39)	I196M	probably benign	Het
Habp2	A	G	19: 56,295,253 (GRCm39)	D48G	probably benign	Het
Hdc	G	T	2: 126,458,149 (GRCm39)	P58T	probably damaging	Het
Heatr5a	AGCACACTGCAGGAAGCTCACACAGCACAGCATACCTTCAGGAGTGCACACTGCAGGAAGCTCACACAGCACAGCATACCTTCAGGAGAGCACACTGCAGGAAGCTCA	AGCACACTGCAGGAAGCTCACACAGCACAGCATACCTTCAGGAGAGCACACTGCAGGAAGCTCA	12: 51,934,702 (GRCm39)		probably benign	Het
Hnrnpr	G	T	4: 136,063,615 (GRCm39)	V342F	probably damaging	Het
Hyal6	T	A	6: 24,734,929 (GRCm39)	Y287*	probably null	Het
Igsf8	T	C	1: 172,146,525 (GRCm39)	Y571H		Het
Kalrn	A	G	16: 33,854,864 (GRCm39)	S1999P	probably damaging	Het
Lama2	T	A	10: 26,877,170 (GRCm39)	N2672I	probably benign	Het
Lrrc7	T	C	3: 157,867,105 (GRCm39)	R879G	probably damaging	Het
Lrwd1	T	G	5: 136,160,413 (GRCm39)	H307P	probably benign	Het
Mau2	T	C	8: 70,480,153 (GRCm39)	Y318C	probably damaging	Het
Med13	T	C	11: 86,199,727 (GRCm39)	Q660R	probably benign	Het
Mepce	G	C	5: 137,783,759 (GRCm39)	P189R	probably damaging	Het
Mical3	T	A	6: 121,001,758 (GRCm39)	N578I	probably damaging	Het
Mug1	T	C	6: 121,861,635 (GRCm39)	S1366P	probably damaging	Het
Nol11	A	T	11: 107,064,278 (GRCm39)	D511E	possibly damaging	Het
Obscn	T	A	11: 58,994,340 (GRCm39)	H1514L	probably benign	Het
Onecut3	C	A	10: 80,331,887 (GRCm39)	S349*	probably null	Het
Or2l13b	C	T	16: 19,349,026 (GRCm39)	A215T	probably benign	Het
Or4f57	A	G	2: 111,790,584 (GRCm39)	V278A	possibly damaging	Het
Or5ap2b-ps1	A	T	2: 85,693,922 (GRCm39)	I56F	probably damaging	Het
Or5b110-ps1	G	A	19: 13,259,558 (GRCm39)	T288I	unknown	Het
Or7e169	A	G	9: 19,757,816 (GRCm39)	L33P	possibly damaging	Het
Or7g34	T	C	9: 19,478,396 (GRCm39)	I95V	possibly damaging	Het
Or8g18	T	C	9: 39,149,625 (GRCm39)	T32A	probably benign	Het
Patl2	C	T	2: 121,955,374 (GRCm39)	G297E	probably benign	Het
Pdlim5	G	A	3: 142,010,111 (GRCm39)	T168M	probably damaging	Het
Pdzd2	A	C	15: 12,374,621 (GRCm39)	L1838R	probably damaging	Het
Peg10	GC	GCTCC	6: 4,756,452 (GRCm39)		probably benign	Het
Pkd1l3	T	C	8: 110,395,849 (GRCm39)	V2083A	probably damaging	Het
Pkhd1	T	A	1: 20,637,741 (GRCm39)	Y348F	probably damaging	Het
Plekhg5	T	A	4: 152,198,826 (GRCm39)	S1005T	probably benign	Het
Ppp4r1	T	A	17: 66,142,073 (GRCm39)	N709K	probably null	Het
Pramel32	T	A	4: 88,546,219 (GRCm39)	L374F	possibly damaging	Het
Pramel40	G	A	5: 94,464,924 (GRCm39)	V437I	probably benign	Het
Reln	T	C	5: 22,125,508 (GRCm39)	D2725G	possibly damaging	Het
Rnf41	T	A	10: 128,274,299 (GRCm39)	I317K	probably benign	Het
Rxfp2	T	C	5: 149,979,444 (GRCm39)	V268A	possibly damaging	Het
Sema5a	A	G	15: 32,679,373 (GRCm39)	H884R	probably damaging	Het
Serpinh1	A	T	7: 98,996,484 (GRCm39)	M236K	probably damaging	Het
Sh3pxd2a	A	G	19: 47,255,610 (GRCm39)	L1064P	probably damaging	Het
Skint6	T	C	4: 112,715,375 (GRCm39)	H947R	probably benign	Het
Slc22a3	C	A	17: 12,726,057 (GRCm39)	R52L	probably damaging	Het
Slc38a1	A	G	15: 96,487,965 (GRCm39)	L180P	probably damaging	Het
Slc4a3	T	C	1: 75,533,612 (GRCm39)	V1078A	probably damaging	Het
Snx30	T	A	4: 59,879,241 (GRCm39)	V160E	probably damaging	Het
Spata18	A	T	5: 73,829,840 (GRCm39)	I332F		Het
Stard9	C	G	2: 120,534,564 (GRCm39)	P3607R	probably damaging	Het
Svep1	T	A	4: 58,084,144 (GRCm39)	Y1876F	possibly damaging	Het
Sytl1	A	G	4: 132,986,291 (GRCm39)		probably null	Het
Tacc2	A	C	7: 130,366,041 (GRCm39)	K567Q	probably damaging	Het
Tfr2	A	G	5: 137,575,769 (GRCm39)	D295G	possibly damaging	Het
Tmem53	C	A	4: 117,125,122 (GRCm39)	H78Q	probably benign	Het
Tnnt2	G	A	1: 135,768,640 (GRCm39)	E10K	unknown	Het
Top2a	T	A	11: 98,902,970 (GRCm39)	I406F	probably damaging	Het
Ttc1	C	A	11: 43,621,305 (GRCm39)	R292I		Het
Ubr1	T	G	2: 120,703,627 (GRCm39)	T1568P	probably damaging	Het
Usp25	T	G	16: 76,852,076 (GRCm39)	V197G	probably damaging	Het
Usp9y	A	T	Y: 1,432,188 (GRCm39)	N432K	probably benign	Het
Vmn2r26	T	A	6: 124,038,137 (GRCm39)	Y571N	probably damaging	Het
Zfp7	T	C	15: 76,775,484 (GRCm39)	S509P	probably damaging	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
R4908:Slc12a3	UTSW	8	95,075,216 (GRCm39)	missense	possibly damaging	0.76
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
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'- CTGAATGCCAGACCTAAGTGTTAAG -3'
(R):5'- ATTCCAGAAGCCCAGGGATG -3'

Sequencing Primer
(F):5'- CCAGACCTAAGTGTTAAGGGCTG -3'
(R):5'- TGGGGAGACATGCTGGAACC -3'

Posted On

2022-07-18