Mutagenetix > Incidental Mutations

Incidental Mutation 'R4627:Slc12a3'

348878

Institutional Source

Beutler Lab

Gene Symbol

Slc12a3

Ensembl Gene

ENSMUSG00000031766

Gene Name

solute carrier family 12, member 3

Synonyms

NCC, TSC

MMRRC Submission

041892-MU

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4627 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

94329201-94366214 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 94329384 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Phenylalanine at position 49 (L49F)

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: L49F

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: L49F

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

probably benign
Transcript: ENSMUST00000212134
AA Change: L49F

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212800

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.3%
20x: 95.4%

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: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2010111I01Rik	T	C	13: 63,068,092	S393P	probably benign	Het
Adam6a	A	T	12: 113,544,949	D314V	probably benign	Het
Adamts18	C	T	8: 113,773,168	W371*	probably null	Het
Adamtsl2	T	A	2: 27,093,585	L331Q	probably damaging	Het
Akr1c13	G	T	13: 4,197,870	V214F	probably damaging	Het
Aldoart1	T	C	4: 72,852,443	T43A	probably benign	Het
Alkbh2	C	T	5: 114,124,226	E148K	probably damaging	Het
Ano7	T	C	1: 93,375,185	I15T	probably benign	Het
Aox3	A	T	1: 58,125,035	T155S	probably damaging	Het
Ap2a1	C	T	7: 44,904,419	V535M	probably damaging	Het
Apbb2	C	T	5: 66,400,076		probably null	Het
Astn1	C	A	1: 158,502,251	H225Q	possibly damaging	Het
Atm	A	G	9: 53,456,506	I2439T	possibly damaging	Het
Atp1b2	T	A	11: 69,601,334	I263F	probably damaging	Het
Ccdc184	A	T	15: 98,168,757	N148Y	probably benign	Het
Cdca7	TGAAGAAGAAGAAGAAGAAGAAGAAGAAGAAGA	TGAAGAAGAAGAAGAAGAAGAAGAAGAAGA	2: 72,481,861		probably benign	Het
Cep192	C	G	18: 67,812,369	P180R	probably benign	Het
Cfap46	T	C	7: 139,657,281	Y571C	probably damaging	Het
Cfap46	A	T	7: 139,680,927	L85Q	probably damaging	Het
Chchd6	G	A	6: 89,384,660	L226F	probably damaging	Het
Cnot6l	A	G	5: 96,077,211	V541A	probably benign	Het
Cobl	T	C	11: 12,251,093	E1214G	probably damaging	Het
Cpsf2	G	A	12: 101,989,895	R319Q	probably benign	Het
Csdc2	T	C	15: 81,949,123	V107A	probably benign	Het
Csmd1	A	G	8: 16,697,917	W273R	probably benign	Het
Diexf	T	C	1: 193,107,695	T719A	probably benign	Het
Dnah2	T	A	11: 69,465,376	N2156I	probably damaging	Het
Dsp	A	G	13: 38,168,641	Y165C	probably benign	Het
Exoc1	T	C	5: 76,542,228	V205A	probably benign	Het
Fam98c	T	C	7: 29,155,268	T49A	possibly damaging	Het
Fbln2	G	T	6: 91,259,767	V755L	probably damaging	Het
Fhad1	A	T	4: 141,896,468	V1371D	possibly damaging	Het
Folh1	A	T	7: 86,773,252	M59K	probably benign	Het
Foxf2	A	T	13: 31,626,888	H270L	probably benign	Het
Gm14401	G	A	2: 177,086,316	R65H	probably benign	Het
Gpn1	C	A	5: 31,498,393	Y592*	probably null	Het
Hmcn1	T	G	1: 150,595,894	D4903A	probably benign	Het
Hnf1a	T	C	5: 114,955,871	R220G	probably damaging	Het
Hoxd10	G	A	2: 74,692,292	A105T	probably benign	Het
Kcnd3	C	T	3: 105,658,766	A421V	probably damaging	Het
Kidins220	C	T	12: 25,057,042	T1498I	possibly damaging	Het
Klhl2	G	T	8: 64,758,191	Y274*	probably null	Het
Lmbrd1	A	G	1: 24,705,999	Y140C	probably damaging	Het
Mapk8ip3	G	A	17: 24,903,293	T706I	probably benign	Het
Mast4	A	C	13: 103,334,021	S58A	possibly damaging	Het
Mcm6	T	C	1: 128,351,548	D167G	probably benign	Het
Mmachc	A	T	4: 116,703,471	S276T	probably damaging	Het
Nfat5	A	T	8: 107,369,276	Q1289L	probably damaging	Het
Nlrc4	G	T	17: 74,446,628	F253L	probably damaging	Het
Nr1i3	C	A	1: 171,216,445	A112E	probably benign	Het
Olfr1367	T	C	13: 21,347,464	F179L	probably damaging	Het
Olfr45	T	A	7: 140,691,378	S158T	probably benign	Het
Olfr455	T	A	6: 42,538,441	T194S	possibly damaging	Het
Olfr853	G	T	9: 19,537,673	Q86K	possibly damaging	Het
Orc5	G	T	5: 22,548,005	F10L	probably benign	Het
Pde10a	A	C	17: 8,981,652	D779A	probably damaging	Het
Pde4b	T	C	4: 102,601,605	L486S	probably damaging	Het
Pex2	A	T	3: 5,561,281	I156N	probably damaging	Het
Phtf2	C	T	5: 20,773,740	R63Q	probably damaging	Het
Prag1	A	G	8: 36,103,292	Y343C	probably damaging	Het
Prdm16	A	T	4: 154,367,240	Y170N	probably damaging	Het
Prpf6	A	C	2: 181,601,474	K5T	probably damaging	Het
Ptpn1	A	G	2: 167,967,781	K103R	probably benign	Het
Ralgapa2	A	G	2: 146,361,453	S1159P	possibly damaging	Het
Rapgef3	G	T	15: 97,758,929	D318E	probably damaging	Het
Ripk4	A	T	16: 97,744,026	S474T	probably damaging	Het
Rmi1	A	G	13: 58,409,136	R400G	probably benign	Het
Sec16a	A	G	2: 26,429,393	V1491A	probably damaging	Het
Sec16a	C	T	2: 26,431,068		probably null	Het
Setd7	G	T	3: 51,542,665	N113K	probably damaging	Het
Shank2	C	T	7: 144,411,424	T1502M	probably damaging	Het
Skor1	A	T	9: 63,145,476	C376S	probably damaging	Het
Slc35d3	C	T	10: 19,849,331	V260M	probably damaging	Het
Slc46a1	T	A	11: 78,466,889	V256E	probably benign	Het
Slc6a1	T	C	6: 114,308,106	S127P	probably benign	Het
Syngr4	A	G	7: 45,887,028	L190P	probably damaging	Het
Tagap	G	A	17: 7,926,941		probably null	Het
Tamm41	A	T	6: 115,035,002	N89K	probably benign	Het
Tbc1d31	T	A	15: 57,967,912	M922K	probably benign	Het
Tbk1	T	C	10: 121,568,080	N254S	possibly damaging	Het
Tfec	A	G	6: 16,840,479	S140P	probably damaging	Het
Tnrc18	T	C	5: 142,740,128	E1802G	unknown	Het
Tom1l2	C	T	11: 60,242,707		probably null	Het
Tonsl	T	G	15: 76,637,224	K323Q	probably damaging	Het
Tsnaxip1	A	T	8: 105,841,407	E268D	probably damaging	Het
Ttf1	C	A	2: 29,065,160	H179N	possibly damaging	Het
Ttn	T	C	2: 76,726,173	S30163G	probably damaging	Het
Ube2c	A	G	2: 164,772,173	N143S	possibly damaging	Het
Ugt1a10	G	A	1: 88,218,390	R519Q	probably damaging	Het
Vmn2r9	T	C	5: 108,847,597	Y395C	probably damaging	Het
Vwa8	G	A	14: 79,103,697		probably null	Het
Zfp9	A	G	6: 118,464,976	Y242H	probably damaging	Het

Other mutations in Slc12a3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01823:Slc12a3	APN	8	94357096	missense	probably benign	0.00
IGL01947:Slc12a3	APN	8	94365819	critical splice acceptor site	probably null
IGL02151:Slc12a3	APN	8	94348592	missense	probably benign	0.26
IGL02440:Slc12a3	APN	8	94331682	missense	probably damaging	1.00
IGL03213:Slc12a3	APN	8	94335305	missense	possibly damaging	0.95
IGL03260:Slc12a3	APN	8	94333242	missense	probably damaging	1.00
IGL03306:Slc12a3	APN	8	94351758	missense	possibly damaging	0.72
IGL03329:Slc12a3	APN	8	94365891	missense	possibly damaging	0.67
avaricious	UTSW	8	94330472	missense	probably benign	0.01
Pugilist	UTSW	8	94345773	critical splice acceptor site	probably null
R0131:Slc12a3	UTSW	8	94340883	splice site	probably benign
R0189:Slc12a3	UTSW	8	94356358	missense	probably benign	0.30
R0330:Slc12a3	UTSW	8	94346346	missense	possibly damaging	0.75
R0569:Slc12a3	UTSW	8	94330525	critical splice donor site	probably null
R0715:Slc12a3	UTSW	8	94329433	missense	possibly damaging	0.75
R1248:Slc12a3	UTSW	8	94333277	missense	probably damaging	1.00
R1565:Slc12a3	UTSW	8	94345877	missense	possibly damaging	0.75
R2068:Slc12a3	UTSW	8	94345828	missense	probably damaging	1.00
R2108:Slc12a3	UTSW	8	94340530	missense	probably damaging	0.97
R2273:Slc12a3	UTSW	8	94333287	missense	possibly damaging	0.86
R2274:Slc12a3	UTSW	8	94333287	missense	possibly damaging	0.86
R2275:Slc12a3	UTSW	8	94333287	missense	possibly damaging	0.86
R2433:Slc12a3	UTSW	8	94346316	missense	probably benign	0.00
R3770:Slc12a3	UTSW	8	94353040	missense	probably benign
R4429:Slc12a3	UTSW	8	94343085	missense	probably damaging	1.00
R4431:Slc12a3	UTSW	8	94343085	missense	probably damaging	1.00
R4533:Slc12a3	UTSW	8	94357086	missense	probably null	0.02
R4856:Slc12a3	UTSW	8	94351810	critical splice donor site	probably null
R4886:Slc12a3	UTSW	8	94351810	critical splice donor site	probably null
R4908:Slc12a3	UTSW	8	94348588	missense	possibly damaging	0.76
R5054:Slc12a3	UTSW	8	94346351	missense	probably damaging	1.00
R5299:Slc12a3	UTSW	8	94351789	missense	probably damaging	1.00
R5451:Slc12a3	UTSW	8	94357027	missense	possibly damaging	0.61
R5590:Slc12a3	UTSW	8	94345788	missense	probably damaging	1.00
R5725:Slc12a3	UTSW	8	94330446	missense	probably benign	0.00
R6038:Slc12a3	UTSW	8	94330472	missense	probably benign	0.01
R6038:Slc12a3	UTSW	8	94330472	missense	probably benign	0.01
R6162:Slc12a3	UTSW	8	94345773	critical splice acceptor site	probably null
R6266:Slc12a3	UTSW	8	94358471	missense	possibly damaging	0.93
R6489:Slc12a3	UTSW	8	94335004	missense	possibly damaging	0.96
R6521:Slc12a3	UTSW	8	94343113	missense	possibly damaging	0.84
R6882:Slc12a3	UTSW	8	94365918	missense	possibly damaging	0.51
R7051:Slc12a3	UTSW	8	94365944	missense	probably damaging	1.00
R7510:Slc12a3	UTSW	8	94365849	missense	probably damaging	1.00
R7805:Slc12a3	UTSW	8	94344887	missense	probably damaging	1.00
R8152:Slc12a3	UTSW	8	94330384	missense	probably benign	0.00
R8412:Slc12a3	UTSW	8	94334067	missense	probably damaging	0.99
R8996:Slc12a3	UTSW	8	94329435	missense	probably benign
R9307:Slc12a3	UTSW	8	94334997	missense	probably benign	0.01
R9324:Slc12a3	UTSW	8	94356400	critical splice donor site	probably null

Predicted Primers

PCR Primer
(F):5'- CCTCCTTTGATACCCAGAGC -3'
(R):5'- GATGCCCAGTCATTTTCACAAC -3'

Sequencing Primer
(F):5'- TCCTTTGATACCCAGAGCCATAATGG -3'
(R):5'- ACAGAACATGTTGGGCAATCATGC -3'

Posted On

2015-10-08