Mutagenetix > Incidental Mutation

Incidental Mutation 'R1565:Slc12a3'

175203

Institutional Source

Beutler Lab

Gene Symbol

Slc12a3

Ensembl Gene

ENSMUSG00000031766

Gene Name

solute carrier family 12, member 3

Synonyms

TSC, NCC

MMRRC Submission

039604-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1565 (G1)

Quality Score

220

Status

Not validated

Chromosome

Chromosomal Location

95055829-95092842 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 95072505 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 674 (H674Q)

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: H674Q

PolyPhen 2 Score 0.090 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: H674Q

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: H674Q

PolyPhen 2 Score 0.752 (Sensitivity: 0.85; Specificity: 0.92)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212915

Coding Region Coverage

1x: 99.0%
3x: 98.1%
10x: 95.5%
20x: 90.0%

Validation Efficiency

96% (82/85)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810021J22Rik	G	A	11: 58,771,327 (GRCm39)	G270S	probably benign	Het
Abtb1	T	C	6: 88,813,536 (GRCm39)	T401A	probably benign	Het
Adamts14	A	T	10: 61,106,676 (GRCm39)	M148K	probably damaging	Het
Adcy5	A	G	16: 35,089,327 (GRCm39)	E508G	probably damaging	Het
Ankfy1	T	A	11: 72,648,144 (GRCm39)	L875H	probably damaging	Het
Cacng3	A	T	7: 122,367,624 (GRCm39)	D168V	probably damaging	Het
Clpb	G	A	7: 101,434,668 (GRCm39)	R488Q	probably benign	Het
Cltrn	A	G	X: 162,901,230 (GRCm39)	D184G	possibly damaging	Het
Cpxm2	A	T	7: 131,663,874 (GRCm39)	Y350N	probably damaging	Het
D130040H23Rik	T	A	8: 69,755,812 (GRCm39)	*406R	probably null	Het
Dnah10	T	A	5: 124,906,678 (GRCm39)	D4236E	probably damaging	Het
Dpf3	T	A	12: 83,417,391 (GRCm39)	Y27F	probably damaging	Het
Esp4	T	C	17: 40,913,486 (GRCm39)	*118Q	probably null	Het
Fam222b	T	C	11: 78,045,488 (GRCm39)	S222P	possibly damaging	Het
Flnc	T	C	6: 29,455,170 (GRCm39)	V1933A	probably damaging	Het
Gem	T	C	4: 11,713,709 (GRCm39)	F282L	possibly damaging	Het
Gli2	T	C	1: 118,769,660 (GRCm39)	T631A	possibly damaging	Het
Gpld1	T	A	13: 25,140,051 (GRCm39)	V116E	probably damaging	Het
Gpr176	A	G	2: 118,110,695 (GRCm39)	M188T	probably benign	Het
Grk5	T	C	19: 61,078,410 (GRCm39)	V489A	probably damaging	Het
Hpdl	T	C	4: 116,678,080 (GRCm39)	N127S	probably damaging	Het
Hsd17b8	C	T	17: 34,246,469 (GRCm39)	V105I	possibly damaging	Het
Id4	G	T	13: 48,415,770 (GRCm39)	V151L	possibly damaging	Het
Kcnh8	G	T	17: 53,263,909 (GRCm39)	G802V	probably benign	Het
Lamc1	C	A	1: 153,118,489 (GRCm39)	S894I	probably benign	Het
Larp1b	A	G	3: 40,926,819 (GRCm39)	N184S	probably damaging	Het
Lhx1	A	T	11: 84,410,647 (GRCm39)	S226T	probably benign	Het
Lmo7	A	T	14: 102,124,957 (GRCm39)	Q472L	probably damaging	Het
Mog	G	C	17: 37,328,474 (GRCm39)	N152K	possibly damaging	Het
Mttp	A	G	3: 137,822,166 (GRCm39)		probably null	Het
Mycbp2	A	G	14: 103,489,945 (GRCm39)	V953A	possibly damaging	Het
Myo3a	A	T	2: 22,345,091 (GRCm39)	Y509F	probably damaging	Het
Myo9b	A	G	8: 71,767,836 (GRCm39)	N303S	possibly damaging	Het
Nek3	T	C	8: 22,622,217 (GRCm39)		probably null	Het
Nlrc4	A	T	17: 74,748,926 (GRCm39)	D771E	probably benign	Het
Nup160	A	T	2: 90,552,405 (GRCm39)	N1127I	possibly damaging	Het
Oas1h	A	T	5: 121,000,663 (GRCm39)	N91I	probably damaging	Het
Or13p4	T	A	4: 118,547,389 (GRCm39)	N87Y	probably damaging	Het
Or4c120	A	T	2: 89,000,971 (GRCm39)	V195D	probably benign	Het
Or4c121	G	T	2: 89,024,227 (GRCm39)	S50R	probably damaging	Het
Parp4	T	C	14: 56,827,329 (GRCm39)		probably benign	Het
Pi4ka	G	A	16: 17,099,764 (GRCm39)	C96Y	probably null	Het
Pira2	A	T	7: 3,847,548 (GRCm39)	F47Y	probably damaging	Het
Pkhd1	C	A	1: 20,417,681 (GRCm39)	G2490V	probably damaging	Het
Plekhg1	C	T	10: 3,890,526 (GRCm39)	T394I	probably damaging	Het
Pramel22	G	A	4: 143,382,187 (GRCm39)	Q170*	probably null	Het
Psmd1	T	C	1: 86,019,719 (GRCm39)		probably benign	Het
Rab3ip	A	T	10: 116,775,128 (GRCm39)	C77S	probably benign	Het
Reln	A	T	5: 22,130,211 (GRCm39)	M2700K	probably benign	Het
Rfx1	A	G	8: 84,800,575 (GRCm39)	T59A	probably benign	Het
Ric8b	G	T	10: 84,815,963 (GRCm39)	V405L	probably benign	Het
Rufy3	G	T	5: 88,788,491 (GRCm39)	A479S	probably damaging	Het
Sardh	A	T	2: 27,132,731 (GRCm39)	Y166N	probably damaging	Het
Slamf6	T	G	1: 171,761,975 (GRCm39)	V132G	possibly damaging	Het
Sned1	G	A	1: 93,209,376 (GRCm39)	V830M	possibly damaging	Het
Srsf9	A	G	5: 115,465,429 (GRCm39)	N21S	possibly damaging	Het
Stkld1	A	T	2: 26,840,102 (GRCm39)	T391S	probably benign	Het
Sumf2	C	A	5: 129,888,755 (GRCm39)	N230K	probably damaging	Het
Tbc1d22a	T	C	15: 86,119,770 (GRCm39)	V22A	possibly damaging	Het
Thsd7b	T	A	1: 129,523,778 (GRCm39)	S194T	possibly damaging	Het
Tnn	T	A	1: 159,924,835 (GRCm39)	Y1173F	probably damaging	Het
Top2a	A	G	11: 98,891,880 (GRCm39)	F1122L	probably damaging	Het
Trappc9	G	A	15: 72,897,816 (GRCm39)	R377W	probably damaging	Het
Trim39	G	A	17: 36,579,746 (GRCm39)	R70W	probably damaging	Het
Ttn	G	A	2: 76,624,605 (GRCm39)	T15289I	probably damaging	Het
Ugt2b38	A	T	5: 87,559,773 (GRCm39)	V373E	probably damaging	Het
Usp54	A	G	14: 20,657,227 (GRCm39)	S24P	probably damaging	Het
Vmn2r27	C	T	6: 124,208,593 (GRCm39)	G51S	probably benign	Het
Xylt2	C	T	11: 94,558,420 (GRCm39)	A579T	probably benign	Het
Zbtb21	A	G	16: 97,753,627 (GRCm39)	S247P	probably benign	Het
Zc3h7b	C	T	15: 81,661,289 (GRCm39)	P376L	probably benign	Het
Zfp251	T	A	15: 76,737,238 (GRCm39)	R613S	probably damaging	Het
Zfp251	C	T	15: 76,737,239 (GRCm39)	R613K	possibly damaging	Het
Zfp91	T	C	19: 12,756,439 (GRCm39)	D135G	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
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'- TGCTGACTCCCAACATAAAGGTTCG -3'
(R):5'- GCCAGATTCTGCTAGGTCCACTTC -3'

Sequencing Primer
(F):5'- GAGTCAGAGAGCATCTTCCTTTAG -3'
(R):5'- AGGTCCACTTCCCCTGC -3'

Posted On

2014-04-24