Mutagenetix > Incidental Mutation

Incidental Mutation 'R7051:Slc12a3'

547591

Institutional Source

Beutler Lab

Gene Symbol

Slc12a3

Ensembl Gene

ENSMUSG00000031766

Gene Name

solute carrier family 12, member 3

Synonyms

TSC, NCC

MMRRC Submission

045148-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7051 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

95055829-95092842 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 95092572 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 998 (T998A)

Ref Sequence

ENSEMBL: ENSMUSP00000034218 (fasta)

Gene Model

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

AlphaFold

P59158

Predicted Effect

probably damaging
Transcript: ENSMUST00000034218
AA Change: T998A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: T998A

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

Meta Mutation Damage Score

0.4049

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

95% (80/84)

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: 81 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5930422O12Rik	C	T	8: 33,919,201 (GRCm39)	S7L	unknown	Het
Aggf1	T	C	13: 95,488,125 (GRCm39)	K674R	possibly damaging	Het
Ampd1	T	C	3: 102,997,389 (GRCm39)	F264L	probably damaging	Het
Ankle1	A	T	8: 71,860,387 (GRCm39)	S302C	probably damaging	Het
Ankrd17	G	A	5: 90,514,310 (GRCm39)		probably benign	Het
Arhgap18	T	A	10: 26,725,917 (GRCm39)	N47K	possibly damaging	Het
Atp5pb	T	C	3: 105,851,083 (GRCm39)	N205D	probably benign	Het
Atp8b3	C	T	10: 80,355,858 (GRCm39)	E1285K	probably benign	Het
Atp8b3	C	A	10: 80,365,552 (GRCm39)	V401L	probably damaging	Het
Cacna1a	G	A	8: 85,356,544 (GRCm39)	R1929Q	possibly damaging	Het
Cadm2	C	T	16: 66,679,767 (GRCm39)	S22N	possibly damaging	Het
Ccdc177	C	T	12: 80,805,927 (GRCm39)	V116M	probably damaging	Het
Cdhr18	A	G	14: 13,828,486 (GRCm38)	V758A		Het
Cdkl2	A	T	5: 92,181,084 (GRCm39)	I185N	probably damaging	Het
Cfhr2	T	A	1: 139,738,716 (GRCm39)	I282L	probably benign	Het
Clns1a	T	A	7: 97,361,824 (GRCm39)		probably null	Het
Commd2	A	T	3: 57,554,107 (GRCm39)	I198N	probably damaging	Het
Creb3l2	C	T	6: 37,313,200 (GRCm39)	V365I	possibly damaging	Het
Dcaf6	A	T	1: 165,251,886 (GRCm39)	N79K	possibly damaging	Het
Dlg5	T	C	14: 24,196,263 (GRCm39)	N1622D	possibly damaging	Het
Dock7	C	T	4: 98,834,969 (GRCm39)	R1802H	probably damaging	Het
Dpy19l2	T	C	9: 24,495,789 (GRCm39)	K643R	probably benign	Het
Dscam	G	A	16: 96,620,986 (GRCm39)	T574M	probably benign	Het
Fam209	A	G	2: 172,315,969 (GRCm39)	T115A	probably damaging	Het
Fastkd5	C	T	2: 130,456,337 (GRCm39)	C751Y	probably damaging	Het
Fat3	C	A	9: 16,289,123 (GRCm39)	L133F	probably damaging	Het
Fcsk	A	T	8: 111,616,971 (GRCm39)	I393N	probably damaging	Het
Frmd6	T	C	12: 70,944,170 (GRCm39)	V516A	possibly damaging	Het
Fry	G	A	5: 150,318,634 (GRCm39)	D955N	possibly damaging	Het
Gm7298	T	C	6: 121,751,993 (GRCm39)		probably null	Het
Golga7b	T	A	19: 42,256,899 (GRCm39)	*168R	probably null	Het
Golim4	T	A	3: 75,800,309 (GRCm39)	Q395L	probably benign	Het
Gxylt2	T	A	6: 100,781,537 (GRCm39)	L404*	probably null	Het
H1f4	A	G	13: 23,806,422 (GRCm39)	V20A	probably benign	Het
Ighmbp2	G	T	19: 3,311,462 (GRCm39)	S984R	probably damaging	Het
Irf8	C	T	8: 121,466,581 (GRCm39)	R9W	probably damaging	Het
Itga4	T	C	2: 79,148,470 (GRCm39)	V788A	possibly damaging	Het
Kifap3	G	A	1: 163,621,649 (GRCm39)	R99H	probably damaging	Het
Kiss1r	T	C	10: 79,754,688 (GRCm39)	S61P	probably damaging	Het
Krtap6-1	A	T	16: 88,828,606 (GRCm39)	M1L	unknown	Het
Large2	A	T	2: 92,197,367 (GRCm39)	M411K	probably damaging	Het
Lcor	A	G	19: 41,574,191 (GRCm39)	D982G	probably benign	Het
Lingo1	A	G	9: 56,527,467 (GRCm39)	V374A	probably benign	Het
Lrch1	A	G	14: 75,022,962 (GRCm39)	V637A	probably damaging	Het
Lyar	T	C	5: 38,382,024 (GRCm39)	V2A	probably damaging	Het
Nell1	C	T	7: 50,098,592 (GRCm39)	S298L	unknown	Het
Ogfod3	T	A	11: 121,086,031 (GRCm39)	I188F	probably damaging	Het
Opa3	C	A	7: 18,978,961 (GRCm39)	A142E	possibly damaging	Het
Or5b123	T	A	19: 13,596,769 (GRCm39)	M81K	possibly damaging	Het
Or5k1	T	C	16: 58,617,538 (GRCm39)	T224A	probably benign	Het
Pald1	T	C	10: 61,159,125 (GRCm39)	R769G	probably benign	Het
Pappa2	T	A	1: 158,784,753 (GRCm39)	T86S	unknown	Het
Papss1	T	C	3: 131,307,811 (GRCm39)	Y266H	probably damaging	Het
Pcdhga7	C	A	18: 37,849,994 (GRCm39)	A667D	probably damaging	Het
Pcsk5	T	A	19: 17,411,095 (GRCm39)	T1766S	probably benign	Het
Pds5b	T	A	5: 150,717,747 (GRCm39)	N1129K	possibly damaging	Het
Pop7	T	C	5: 137,499,952 (GRCm39)	N127S	probably damaging	Het
Ppfibp2	A	G	7: 107,316,925 (GRCm39)	E300G	probably damaging	Het
Ppp4r3b	A	G	11: 29,132,507 (GRCm39)	K87E	probably damaging	Het
Psmd3	T	A	11: 98,573,659 (GRCm39)	M35K	possibly damaging	Het
Pus7	A	G	5: 23,980,677 (GRCm39)	V191A	probably damaging	Het
Rptor	C	T	11: 119,765,012 (GRCm39)		probably benign	Het
Sacs	A	G	14: 61,446,377 (GRCm39)	M2808V	probably benign	Het
Scube3	G	A	17: 28,386,573 (GRCm39)	V831I	probably benign	Het
Sin3a	A	T	9: 57,011,218 (GRCm39)	N492Y	probably damaging	Het
Slc4a1	T	C	11: 102,247,084 (GRCm39)	N501S	probably benign	Het
Sltm	G	A	9: 70,466,348 (GRCm39)	G94R	probably damaging	Het
Smc4	T	A	3: 68,934,835 (GRCm39)	W650R	probably damaging	Het
Smg7	A	G	1: 152,724,601 (GRCm39)	S527P	probably damaging	Het
Tcf20	T	C	15: 82,740,279 (GRCm39)	N391D	probably damaging	Het
Tiam2	G	A	17: 3,498,758 (GRCm39)	V845M	probably damaging	Het
Tln2	A	G	9: 67,253,699 (GRCm39)	F793L	probably benign	Het
Uckl1	T	C	2: 181,216,037 (GRCm39)	I193V	probably damaging	Het
Ugt1a5	A	G	1: 88,094,077 (GRCm39)	M102V	probably benign	Het
Usp38	G	A	8: 81,727,750 (GRCm39)	P328S	possibly damaging	Het
Vmn1r189	A	G	13: 22,286,285 (GRCm39)	V184A	possibly damaging	Het
Vps13d	C	A	4: 144,889,914 (GRCm39)	A597S	probably benign	Het
Wdr47	T	A	3: 108,525,840 (GRCm39)	L121Q	probably damaging	Het
Wiz	A	G	17: 32,580,507 (GRCm39)	S315P	probably damaging	Het
Zc3h13	T	C	14: 75,568,597 (GRCm39)	S1297P	probably damaging	Het
Zfp27	AATCCGCTTGTGCA	AA	7: 29,594,446 (GRCm39)		probably benign	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
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'- TTCAGAAGGCAAGCCCTGTG -3'
(R):5'- AAGGTCCAGAAAGTGTGTCTGATG -3'

Sequencing Primer
(F):5'- CTGGGCTGTGTGGGAAAGC -3'
(R):5'- ATGGGGGTTCAGTCAGCC -3'

Posted On

2019-05-13