Incidental Mutation 'R8152:Slc12a3'
ID 633020
Institutional Source Beutler Lab
Gene Symbol Slc12a3
Ensembl Gene ENSMUSG00000031766
Gene Name solute carrier family 12, member 3
Synonyms TSC, NCC
MMRRC Submission 067578-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R8152 (G1)
Quality Score 225.009
Status Validated
Chromosome 8
Chromosomal Location 95055829-95092842 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 95057012 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glycine to Aspartic acid at position 95 (G95D)
Ref Sequence ENSEMBL: ENSMUSP00000034218 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000034218] [ENSMUST00000212134]
AlphaFold P59158
Predicted Effect probably benign
Transcript: ENSMUST00000034218
AA Change: G95D

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
SMART Domains Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: G95D

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 probably benign
Transcript: ENSMUST00000212134
AA Change: G95D

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
Coding Region Coverage
  • 1x: 99.8%
  • 3x: 99.6%
  • 10x: 98.3%
  • 20x: 92.4%
Validation Efficiency 99% (74/75)
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: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aasdh A G 5: 77,044,305 (GRCm39) L195P probably damaging Het
Adgrb1 T C 15: 74,413,460 (GRCm39) V548A probably benign Het
Adgrb1 T C 15: 74,416,849 (GRCm39) I752T probably damaging Het
Adgrb3 T C 1: 25,260,838 (GRCm39) probably null Het
Adh6a G T 3: 138,033,275 (GRCm39) probably null Het
Aldh18a1 A G 19: 40,553,456 (GRCm39) S431P probably benign Het
Arap3 T C 18: 38,124,410 (GRCm39) R310G possibly damaging Het
Atad5 T C 11: 79,985,996 (GRCm39) V361A possibly damaging Het
Atp8a1 C A 5: 67,919,925 (GRCm39) M380I Het
Calcrl C T 2: 84,169,593 (GRCm39) V363M possibly damaging Het
Camsap1 G T 2: 25,830,253 (GRCm39) D490E probably damaging Het
Cd72 T A 4: 43,452,601 (GRCm39) I131F possibly damaging Het
Cdh2 C T 18: 16,762,576 (GRCm39) G513D probably benign Het
Cela1 T C 15: 100,580,822 (GRCm39) T145A probably benign Het
Cep250 A G 2: 155,811,227 (GRCm39) T358A probably benign Het
Cfap99 C T 5: 34,480,735 (GRCm39) R462C probably damaging Het
Cmtm1 A G 8: 105,036,573 (GRCm39) S19P possibly damaging Het
Crebbp A T 16: 3,902,945 (GRCm39) M2098K possibly damaging Het
Csmd3 T C 15: 47,532,860 (GRCm39) probably null Het
Ctsm C G 13: 61,687,463 (GRCm39) V100L probably benign Het
Cyp2c67 C A 19: 39,628,452 (GRCm39) C164F probably benign Het
Cyp2d11 T C 15: 82,276,688 (GRCm39) I84V probably benign Het
Cyp2j11 T C 4: 96,195,529 (GRCm39) D389G probably damaging Het
Dctd A G 8: 48,564,725 (GRCm39) D9G probably benign Het
Fam221a C A 6: 49,355,490 (GRCm39) F197L probably damaging Het
Fbxl4 T G 4: 22,427,225 (GRCm39) C489G possibly damaging Het
Fmn1 C T 2: 113,196,037 (GRCm39) T579M unknown Het
Fndc3a G A 14: 72,811,820 (GRCm39) L337F probably damaging Het
Frmpd2 A G 14: 33,265,244 (GRCm39) probably null Het
Gdnf C T 15: 7,864,243 (GRCm39) S218L probably damaging Het
Gen1 A G 12: 11,293,266 (GRCm39) F444L probably damaging Het
Gk5 A T 9: 96,056,756 (GRCm39) D391V probably damaging Het
Gys2 T C 6: 142,373,136 (GRCm39) T612A probably benign Het
Il17ra A G 6: 120,459,063 (GRCm39) D738G probably benign Het
Isx T C 8: 75,616,627 (GRCm39) F85L probably damaging Het
Kcnh5 T C 12: 74,944,633 (GRCm39) D872G possibly damaging Het
Kif26b T G 1: 178,506,794 (GRCm39) V290G possibly damaging Het
Ksr2 T C 5: 117,809,523 (GRCm39) C429R probably damaging Het
Loxhd1 A C 18: 77,476,095 (GRCm39) I1121L possibly damaging Het
Map2 T C 1: 66,453,902 (GRCm39) F931L probably benign Het
Mepce T C 5: 137,782,935 (GRCm39) I464V probably benign Het
Mpo G T 11: 87,692,475 (GRCm39) V538L probably benign Het
Mtarc2 T A 1: 184,573,509 (GRCm39) M130L possibly damaging Het
Mtrex T A 13: 113,009,517 (GRCm39) K961* probably null Het
Myom1 T C 17: 71,391,290 (GRCm39) V933A probably damaging Het
Nckap1l T G 15: 103,386,957 (GRCm39) probably null Het
Ncmap C A 4: 135,104,375 (GRCm39) M19I possibly damaging Het
Neb T A 2: 52,073,848 (GRCm39) I5920F probably benign Het
Nnt C T 13: 119,511,212 (GRCm39) V355I probably benign Het
Nr1i2 C T 16: 38,073,326 (GRCm39) G217S probably damaging Het
Nsd1 A G 13: 55,458,180 (GRCm39) R2098G possibly damaging Het
Parp4 A G 14: 56,884,703 (GRCm39) T1261A probably benign Het
Pcgf3 A T 5: 108,635,723 (GRCm39) N131I probably benign Het
Plcb2 C T 2: 118,541,302 (GRCm39) D1012N probably benign Het
Plcl2 T C 17: 50,914,689 (GRCm39) I566T probably damaging Het
Plekha1 G A 7: 130,510,102 (GRCm39) A283T probably damaging Het
Prag1 A T 8: 36,567,079 (GRCm39) M77L possibly damaging Het
Rhbdl2 A T 4: 123,718,711 (GRCm39) I222L probably benign Het
Rnh1 A C 7: 140,740,617 (GRCm39) V446G probably damaging Het
Sash1 C T 10: 8,626,805 (GRCm39) R193H possibly damaging Het
Sgf29 G T 7: 126,271,826 (GRCm39) V284L possibly damaging Het
Slc17a7 T C 7: 44,819,714 (GRCm39) V172A probably damaging Het
Spta1 T C 1: 174,045,510 (GRCm39) V1556A probably benign Het
Tex15 G A 8: 34,062,921 (GRCm39) E784K possibly damaging Het
Ttn T C 2: 76,673,132 (GRCm39) E11224G unknown Het
Wipf1 G A 2: 73,267,879 (GRCm39) P173L possibly damaging Het
Zdbf2 C T 1: 63,345,572 (GRCm39) T1317I possibly damaging Het
Zfat C T 15: 67,973,355 (GRCm39) A1147T probably benign Het
Zfp217 G A 2: 169,961,571 (GRCm39) S252F possibly damaging Het
Zhx3 T G 2: 160,622,695 (GRCm39) I491L probably benign Het
Zranb3 T C 1: 127,882,732 (GRCm39) D1061G probably 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
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
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'- GAATGCTCAGCTTGCTTGCTC -3'
(R):5'- CTAGGGCCTGAGAGTCAAAG -3'

Sequencing Primer
(F):5'- AGCTTGCTTGCTCTCTCTGGTG -3'
(R):5'- AGGCTGAATGGGGCTCTAC -3'
Posted On 2020-06-30