Mutagenetix > Incidental Mutation

Incidental Mutation 'R2275:Slc12a3'

242732

Institutional Source

Beutler Lab

Gene Symbol

Slc12a3

Ensembl Gene

ENSMUSG00000031766

Gene Name

solute carrier family 12, member 3

Synonyms

TSC, NCC

MMRRC Submission

040274-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R2275 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

95055829-95092842 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 95059915 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 187 (I187N)

Ref Sequence

ENSEMBL: ENSMUSP00000148455 (fasta)

Gene Model

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

AlphaFold

P59158

Predicted Effect

possibly damaging
Transcript: ENSMUST00000034218
AA Change: I187N

PolyPhen 2 Score 0.812 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: I187N

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: I187N

PolyPhen 2 Score 0.858 (Sensitivity: 0.83; Specificity: 0.93)

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.6%

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2300003K06Rik	A	T	11: 99,728,667 (GRCm39)	C59S	possibly damaging	Het
Abca5	A	T	11: 110,166,107 (GRCm39)	N1556K	possibly damaging	Het
Ackr1	T	C	1: 173,160,052 (GRCm39)	N156D	probably benign	Het
Aco2	C	T	15: 81,779,465 (GRCm39)	R57C	probably benign	Het
Adamtsl3	A	T	7: 82,255,766 (GRCm39)	S1593C	probably benign	Het
Adgrb2	G	A	4: 129,900,647 (GRCm39)	G333D	probably damaging	Het
Arhgef7	T	A	8: 11,865,010 (GRCm39)	F374Y	possibly damaging	Het
Atxn7	T	A	14: 14,013,268 (GRCm38)	M62K	possibly damaging	Het
C87436	G	A	6: 86,422,582 (GRCm39)	R52H	probably damaging	Het
Cacna1g	T	A	11: 94,306,762 (GRCm39)	E1842V	probably damaging	Het
Cdh4	T	C	2: 179,532,640 (GRCm39)	S701P	probably damaging	Het
Cdr2	A	T	7: 120,557,732 (GRCm39)	H264Q	possibly damaging	Het
Cecr2	C	T	6: 120,733,702 (GRCm39)	S563L	probably benign	Het
Cfap276	A	G	3: 108,449,819 (GRCm39)	N33D	possibly damaging	Het
Col12a1	A	T	9: 79,542,709 (GRCm39)	V2352E	probably damaging	Het
Col9a2	C	G	4: 120,911,455 (GRCm39)	R599G	probably damaging	Het
Crygs	C	T	16: 22,624,301 (GRCm39)	G102D	possibly damaging	Het
Csad	G	T	15: 102,095,557 (GRCm39)	R167S	probably damaging	Het
Dnlz	A	T	2: 26,241,483 (GRCm39)	C82S	probably damaging	Het
Ehmt2	T	A	17: 35,129,691 (GRCm39)	N951K	possibly damaging	Het
Emilin1	C	T	5: 31,075,082 (GRCm39)	P441L	possibly damaging	Het
Enpp2	A	C	15: 54,761,190 (GRCm39)	Y221D	probably damaging	Het
Exoc3l	A	T	8: 106,017,079 (GRCm39)		probably null	Het
F11	T	C	8: 45,705,184 (GRCm39)	D119G	possibly damaging	Het
Faiml	T	C	9: 99,111,612 (GRCm39)	Y149C	probably benign	Het
Fn1	C	T	1: 71,653,102 (GRCm39)	G1296R	probably null	Het
Glg1	A	T	8: 111,895,353 (GRCm39)	Y819*	probably null	Het
Gm11568	A	G	11: 99,749,070 (GRCm39)	S92G	unknown	Het
Gm28042	A	C	2: 119,867,310 (GRCm39)	Q465P	probably damaging	Het
Gpatch1	A	T	7: 34,988,103 (GRCm39)	S678T	probably benign	Het
Gpr158	A	T	2: 21,831,674 (GRCm39)	M925L	probably benign	Het
Hecw1	T	C	13: 14,520,653 (GRCm39)	T195A	probably benign	Het
Hoxd1	A	G	2: 74,594,501 (GRCm39)	K252R	probably damaging	Het
Iqck	G	A	7: 118,498,880 (GRCm39)	D173N	possibly damaging	Het
Kcnh1	T	G	1: 192,019,829 (GRCm39)	V358G	probably damaging	Het
Kifap3	T	A	1: 163,696,327 (GRCm39)	V652D	possibly damaging	Het
Knl1	C	A	2: 118,902,762 (GRCm39)	Q1488K	probably damaging	Het
Map4k1	T	A	7: 28,701,382 (GRCm39)	H729Q	probably damaging	Het
Marchf1	T	A	8: 66,840,151 (GRCm39)	N311K	probably benign	Het
Mypn	A	G	10: 62,966,848 (GRCm39)	F943L	probably damaging	Het
Nkpd1	A	G	7: 19,257,822 (GRCm39)	I534V	probably benign	Het
Nrarp	T	C	2: 25,071,421 (GRCm39)	V100A	possibly damaging	Het
Nt5c1a	T	C	4: 123,109,873 (GRCm39)	F324S	probably damaging	Het
Ntrk2	T	A	13: 59,009,165 (GRCm39)	Y319N	probably damaging	Het
Odad2	C	A	18: 7,223,676 (GRCm39)	G456W	probably benign	Het
Or5d41	A	G	2: 88,055,167 (GRCm39)	F70L	probably benign	Het
Parg	A	G	14: 32,017,195 (GRCm39)	D384G	probably damaging	Het
Pde7b	T	A	10: 20,276,165 (GRCm39)	*460L	probably null	Het
Pigr	G	T	1: 130,774,207 (GRCm39)	V396L	probably benign	Het
Pkhd1	A	G	1: 20,271,073 (GRCm39)	I3160T	possibly damaging	Het
Ppl	T	C	16: 4,912,416 (GRCm39)	S722G	probably benign	Het
Ppp1r26	A	G	2: 28,342,713 (GRCm39)	E781G	possibly damaging	Het
Rptor	T	A	11: 119,647,148 (GRCm39)	C246*	probably null	Het
Rusc2	G	A	4: 43,416,260 (GRCm39)	R522H	probably damaging	Het
Senp7	T	C	16: 56,005,146 (GRCm39)	S927P	probably damaging	Het
Serpinb6d	A	T	13: 33,855,411 (GRCm39)	M362L	probably benign	Het
Setx	GTGGCT	GT	2: 29,044,073 (GRCm39)	1814	probably null	Het
Slc46a1	T	G	11: 78,357,249 (GRCm39)	S101A	probably benign	Het
Slc4a8	A	G	15: 100,705,283 (GRCm39)	M830V	probably benign	Het
Slco4a1	T	C	2: 180,106,529 (GRCm39)	L237P	possibly damaging	Het
Sned1	T	A	1: 93,209,364 (GRCm39)		probably null	Het
Tia1	A	G	6: 86,404,659 (GRCm39)	N298S	probably benign	Het
Tsr1	A	T	11: 74,795,653 (GRCm39)		probably null	Het
Ttc6	G	A	12: 57,749,084 (GRCm39)	V1339I	probably benign	Het
Tyrp1	A	T	4: 80,755,771 (GRCm39)	E180V	probably damaging	Het
Ubr3	T	C	2: 69,846,685 (GRCm39)	V1636A	probably benign	Het
Usp1	T	C	4: 98,818,079 (GRCm39)	L139P	probably damaging	Het
Vmn1r228	A	G	17: 20,996,807 (GRCm39)	L237P	probably damaging	Het
Vmn1r232	A	G	17: 21,134,465 (GRCm39)	L45P	probably benign	Het
Vmn2r2	T	C	3: 64,023,930 (GRCm39)	R884G	probably benign	Het
Vmn2r60	T	A	7: 41,786,251 (GRCm39)	Y351*	probably null	Het
Zbtb7a	G	A	10: 80,980,831 (GRCm39)	V342I	possibly damaging	Het
Zdhhc11	C	A	13: 74,121,871 (GRCm39)	N127K	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
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'- GGTGGCAAACTAAGGCTCAG -3'
(R):5'- CCCAGACTCCGGGAAATAAG -3'

Sequencing Primer
(F):5'- CTCAGAGAAAGGGACTCGGGTC -3'
(R):5'- CCAAGGGCCACAAGGTG -3'

Posted On

2014-10-16