Incidental Mutation 'R0330:Slc12a3'
ID 25993
Institutional Source Beutler Lab
Gene Symbol Slc12a3
Ensembl Gene ENSMUSG00000031766
Gene Name solute carrier family 12, member 3
Synonyms TSC, NCC
MMRRC Submission 038539-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0330 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 95055829-95092842 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 95072974 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Isoleucine at position 699 (N699I)
Ref Sequence ENSEMBL: ENSMUSP00000148455 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034218] [ENSMUST00000212134]
AlphaFold P59158
Predicted Effect probably benign
Transcript: ENSMUST00000034218
AA Change: N699I

PolyPhen 2 Score 0.016 (Sensitivity: 0.95; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: N699I

DomainStartEndE-ValueType
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: N699I

PolyPhen 2 Score 0.752 (Sensitivity: 0.85; Specificity: 0.92)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000212915
Coding Region Coverage
  • 1x: 98.8%
  • 3x: 97.7%
  • 10x: 94.7%
  • 20x: 88.0%
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: 95 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acaa1b T C 9: 118,983,038 (GRCm39) N120S probably damaging Het
Acsbg3 A T 17: 57,190,631 (GRCm39) I400F probably benign Het
Acvr1c T C 2: 58,174,850 (GRCm39) T313A probably damaging Het
Adamtsl3 A T 7: 82,171,198 (GRCm39) D417V probably damaging Het
Adgrf4 A T 17: 42,978,204 (GRCm39) C380S probably damaging Het
AI597479 T G 1: 43,150,277 (GRCm39) L129R probably benign Het
AI661453 G A 17: 47,757,571 (GRCm39) R76Q probably damaging Het
Anpep C T 7: 79,488,004 (GRCm39) E518K probably benign Het
Anxa7 A C 14: 20,519,566 (GRCm39) probably null Het
Arhgap12 T A 18: 6,039,382 (GRCm39) D455V probably damaging Het
Arhgap22 A G 14: 33,091,374 (GRCm39) R650G possibly damaging Het
Arhgef12 A C 9: 42,931,982 (GRCm39) H168Q probably damaging Het
Arhgef2 A G 3: 88,549,808 (GRCm39) H592R probably damaging Het
BC049715 A G 6: 136,817,035 (GRCm39) T92A possibly damaging Het
Bcr C T 10: 75,017,466 (GRCm39) T1209I possibly damaging Het
Bmpr1a C T 14: 34,151,734 (GRCm39) S185N probably benign Het
Calcoco1 A T 15: 102,624,198 (GRCm39) M246K probably benign Het
Capn8 T A 1: 182,457,703 (GRCm39) I689N probably benign Het
Ccno T A 13: 113,126,530 (GRCm39) L333Q probably damaging Het
Cep57 G A 9: 13,728,281 (GRCm39) R148W probably damaging Het
Cftr T A 6: 18,226,096 (GRCm39) M318K probably null Het
Chd3 T G 11: 69,247,159 (GRCm39) D1003A probably damaging Het
Ckmt2 T A 13: 92,011,322 (GRCm39) D96V possibly damaging Het
Cldn13 A G 5: 134,944,176 (GRCm39) V3A probably benign Het
Col17a1 T C 19: 47,658,871 (GRCm39) T413A probably benign Het
Cpne5 A T 17: 29,430,634 (GRCm39) L92H probably damaging Het
Dnaaf2 C A 12: 69,244,518 (GRCm39) R181L probably damaging Het
Erbin C A 13: 104,005,373 (GRCm39) C114F probably damaging Het
Fads2b T A 2: 85,348,895 (GRCm39) R72S probably benign Het
Fanca A T 8: 124,000,911 (GRCm39) C1156* probably null Het
Flot2 T A 11: 77,949,784 (GRCm39) I322N possibly damaging Het
Fstl5 T C 3: 76,615,060 (GRCm39) V707A possibly damaging Het
Gli3 T G 13: 15,898,143 (GRCm39) L741R probably damaging Het
Gmip G T 8: 70,263,468 (GRCm39) S70I probably benign Het
Gnptab T C 10: 88,276,171 (GRCm39) S1153P probably damaging Het
Gramd1a T C 7: 30,837,679 (GRCm39) D360G possibly damaging Het
Gtf2i T C 5: 134,280,740 (GRCm39) E518G probably damaging Het
Hsp90b1 T C 10: 86,530,019 (GRCm39) E226G probably damaging Het
Impg2 A G 16: 56,072,627 (GRCm39) Y353C probably damaging Het
Kank1 A G 19: 25,401,677 (GRCm39) K1095E probably benign Het
Kcnh4 C T 11: 100,648,569 (GRCm39) C45Y probably damaging Het
Kif13b A G 14: 65,040,669 (GRCm39) T1590A probably benign Het
Lpin3 T C 2: 160,747,225 (GRCm39) V827A probably benign Het
Lrp1b A T 2: 40,591,773 (GRCm39) C73* probably null Het
Mcm8 A G 2: 132,661,914 (GRCm39) K83E possibly damaging Het
Med12l A G 3: 59,135,123 (GRCm39) E757G probably damaging Het
Mep1a A G 17: 43,808,789 (GRCm39) probably null Het
Mtor T A 4: 148,568,837 (GRCm39) V1119E probably benign Het
Mybpc2 C T 7: 44,158,453 (GRCm39) A710T possibly damaging Het
Myof A C 19: 37,924,326 (GRCm39) I1297S probably damaging Het
Nacad A G 11: 6,550,903 (GRCm39) S763P probably benign Het
Nbea A G 3: 55,550,238 (GRCm39) V2730A probably benign Het
Nbeal1 A G 1: 60,307,222 (GRCm39) Y1684C probably damaging Het
Optn A T 2: 5,039,066 (GRCm39) N352K possibly damaging Het
Or10k2 A G 8: 84,268,142 (GRCm39) Y123C probably damaging Het
Or2g1 A T 17: 38,106,880 (GRCm39) M182L probably benign Het
Or7g16 A G 9: 18,726,937 (GRCm39) Y218H probably damaging Het
Or9g4b T A 2: 85,616,147 (GRCm39) C97* probably null Het
Pcif1 G T 2: 164,731,364 (GRCm39) R466L probably damaging Het
Phxr2 T C 10: 98,961,979 (GRCm39) probably benign Het
Plaat5 T A 19: 7,614,663 (GRCm39) probably null Het
Plb1 T A 5: 32,512,701 (GRCm39) F1353Y probably damaging Het
Plec A G 15: 76,075,618 (GRCm39) probably null Het
Polr1a T A 6: 71,943,400 (GRCm39) C1212S possibly damaging Het
Primpol A T 8: 47,063,496 (GRCm39) N53K probably damaging Het
Pygo2 T A 3: 89,340,461 (GRCm39) N286K possibly damaging Het
Rttn G A 18: 89,004,204 (GRCm39) probably null Het
Serpinb3b G T 1: 107,087,433 (GRCm39) N25K probably damaging Het
Sidt2 A G 9: 45,866,200 (GRCm39) I2T probably benign Het
Slc25a30 G A 14: 76,000,112 (GRCm39) Q285* probably null Het
Slc4a9 A T 18: 36,668,592 (GRCm39) H724L probably damaging Het
Ssbp2 T A 13: 91,828,698 (GRCm39) probably null Het
Stac3 C A 10: 127,343,616 (GRCm39) probably null Het
Stk32a A G 18: 43,446,566 (GRCm39) K339E probably benign Het
Stoml2 A G 4: 43,030,238 (GRCm39) probably null Het
Syne2 G T 12: 76,013,727 (GRCm39) G2974C probably benign Het
Tbc1d16 A G 11: 119,049,555 (GRCm39) probably null Het
Tfdp2 T G 9: 96,188,946 (GRCm39) F200V probably damaging Het
Tie1 C A 4: 118,341,924 (GRCm39) R175L probably benign Het
Trappc12 A G 12: 28,797,259 (GRCm39) V91A probably benign Het
Trim46 G T 3: 89,143,820 (GRCm39) P536Q probably damaging Het
Tshz3 T A 7: 36,469,458 (GRCm39) D482E probably benign Het
Tspan33 T C 6: 29,711,091 (GRCm39) probably null Het
Unc80 T C 1: 66,713,246 (GRCm39) L2788P possibly damaging Het
Utp20 T A 10: 88,653,841 (GRCm39) T260S probably benign Het
Vmn2r118 G T 17: 55,917,717 (GRCm39) T265K probably damaging Het
Vmn2r98 A C 17: 19,286,609 (GRCm39) H369P probably benign Het
Vps39 A T 2: 120,169,268 (GRCm39) Y245N possibly damaging Het
Vps4a A C 8: 107,769,698 (GRCm39) I336L probably benign Het
Xylb T C 9: 119,210,653 (GRCm39) S379P probably damaging Het
Zbtb37 T C 1: 160,860,066 (GRCm39) T80A probably benign Het
Zfhx3 A G 8: 109,675,589 (GRCm39) D2213G probably damaging Het
Zfp729a G T 13: 67,768,473 (GRCm39) H585Q probably damaging Het
Zfp804b A T 5: 6,821,029 (GRCm39) I642N possibly damaging Het
Zfp804b A T 5: 6,821,994 (GRCm39) N356K possibly damaging Het
Other mutations in Slc12a3
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- ATGCAGCATCTACCCAGGGATAGG -3'
(R):5'- TAAGCTTCAGCGAGACCAGCAC -3'

Sequencing Primer
(F):5'- gaccctacatctaccatccaag -3'
(R):5'- GACCAGCACAGTCTACCGTG -3'
Posted On 2013-04-16