Mutagenetix > Incidental Mutations

Incidental Mutation 'R0373:Slc12a1'

30586

Institutional Source

Beutler Lab

Gene Symbol

Slc12a1

Ensembl Gene

ENSMUSG00000027202

Gene Name

solute carrier family 12, member 1

Synonyms

urehr3, mBSC1, Nkcc2, D630042G03Rik

MMRRC Submission

038579-MU

Accession Numbers

Is this an essential gene?

Probably non essential (E-score: 0.244) question?

Stock #

R0373 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

125152505-125230002 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 125226031 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Serine at position 1013 (T1013S)

Ref Sequence

ENSEMBL: ENSMUSP00000106121 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028630] [ENSMUST00000110494] [ENSMUST00000110495]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000028630
AA Change: T1013S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000028630
Gene: ENSMUSG00000027202
AA Change: T1013S

Domain	Start	End	E-Value	Type
low complexity region	2	15	N/A	INTRINSIC
Pfam:AA_permease_N	82	152	5.3e-22	PFAM
Pfam:AA_permease	173	677	2.3e-152	PFAM
Pfam:AA_permease_2	177	636	2.6e-24	PFAM
coiled coil region	815	843	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000110494
AA Change: T1013S

PolyPhen 2 Score 0.662 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000106120
Gene: ENSMUSG00000027202
AA Change: T1013S

Domain	Start	End	E-Value	Type
low complexity region	2	15	N/A	INTRINSIC
Pfam:AA_permease_N	83	148	3.3e-26	PFAM
Pfam:AA_permease	173	677	2.2e-151	PFAM
Pfam:SLC12	685	1090	1.5e-153	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000110495
AA Change: T1013S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000106121
Gene: ENSMUSG00000027202
AA Change: T1013S

Domain	Start	End	E-Value	Type
low complexity region	2	15	N/A	INTRINSIC
Pfam:AA_permease_N	83	148	3.3e-26	PFAM
Pfam:AA_permease	173	677	1.6e-151	PFAM
Pfam:SLC12	685	1090	1.5e-153	PFAM

Coding Region Coverage

1x: 99.1%
3x: 98.1%
10x: 95.8%
20x: 91.5%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]
PHENOTYPE: Mice homozygous for disruptions in this gene do not survive to weaning and suffer from various metabolic abnormalities related to kidney function. Mice homozygous for an ENU-induced allele exhibit kidney disease, impaired urinary excretion of metabolism products, polyuria, and kidney alterations. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930579F01Rik	A	T	3: 138,173,582	L235Q	probably damaging	Het
Adam6b	T	A	12: 113,490,655	V364D	probably benign	Het
Akap13	T	C	7: 75,609,929	L767P	probably benign	Het
Akap13	T	A	7: 75,730,500	S2193T	probably damaging	Het
Anapc11	T	C	11: 120,605,377	V69A	probably benign	Het
Ankmy1	C	T	1: 92,896,190	R118Q	probably damaging	Het
Ankrd27	T	C	7: 35,638,053	S931P	probably benign	Het
Atp6v1c2	G	A	12: 17,288,168	R280C	probably damaging	Het
Bbs10	T	A	10: 111,300,052	I342N	probably damaging	Het
Calhm2	T	C	19: 47,132,950	D260G	possibly damaging	Het
Camk2a	A	G	18: 60,958,238	E264G	probably damaging	Het
Ccdc146	T	A	5: 21,319,545	M270L	probably benign	Het
Cdc16	A	G	8: 13,779,264	T517A	probably benign	Het
Ces1g	T	C	8: 93,331,193	H160R	probably benign	Het
Chst4	T	C	8: 110,030,394	N196S	probably damaging	Het
Ciz1	A	T	2: 32,367,467	N175Y	probably damaging	Het
Cyb5r4	G	A	9: 87,027,040	V57I	probably damaging	Het
Cyth3	A	G	5: 143,684,426		probably benign	Het
Def6	A	G	17: 28,220,180	E255G	probably damaging	Het
Dhtkd1	T	G	2: 5,911,870	Q665P	probably damaging	Het
Dsg3	A	C	18: 20,539,747	D825A	probably damaging	Het
Eif3m	T	C	2: 105,005,000	T242A	probably benign	Het
Emilin3	A	G	2: 160,909,817	F101L	probably benign	Het
Epha7	A	G	4: 28,935,700		probably null	Het
Fam205a1	T	C	4: 42,851,161	I332V	probably benign	Het
Fbxo45	A	T	16: 32,238,405	Y224N	probably damaging	Het
Fhod3	A	T	18: 25,090,104	M836L	possibly damaging	Het
Fut4	C	A	9: 14,751,210	V263F	probably damaging	Het
Ggt1	C	T	10: 75,579,270	T206M	probably benign	Het
Gls	T	C	1: 52,188,699	R79G	probably damaging	Het
Gm436	A	T	4: 144,686,220	M50K	possibly damaging	Het
Grhl1	T	C	12: 24,581,515	S156P	probably benign	Het
Ipo8	C	T	6: 148,775,042	S983N	probably benign	Het
Kcna7	C	T	7: 45,409,444	A385V	probably damaging	Het
Kpnb1	A	T	11: 97,185,090	L40Q	probably damaging	Het
Matn1	A	T	4: 130,950,106	S209C	probably damaging	Het
Mcc	A	G	18: 44,475,222	I501T	probably benign	Het
Mdp1	A	T	14: 55,659,375	F104L	probably damaging	Het
Mib2	A	T	4: 155,656,288	N626K	probably damaging	Het
Mrgprh	T	C	17: 12,876,956	S28P	possibly damaging	Het
Mup-ps23	T	A	4: 61,856,149		noncoding transcript	Het
Myh15	A	G	16: 49,182,959	T1794A	possibly damaging	Het
Myo18a	C	G	11: 77,821,042	P680A	probably benign	Het
Myom2	G	T	8: 15,098,419	D532Y	possibly damaging	Het
Ndufaf5	A	G	2: 140,170,881	N57S	probably benign	Het
Nectin3	C	T	16: 46,458,187	V282M	probably damaging	Het
Nup188	G	T	2: 30,330,988	D997Y	probably damaging	Het
Olfm3	T	C	3: 115,122,805	V462A	probably damaging	Het
Olfr1044	A	C	2: 86,171,706	F37C	probably damaging	Het
Olfr1225	A	T	2: 89,170,413	F266L	probably benign	Het
Olfr305	A	T	7: 86,363,805	C177*	probably null	Het
Opcml	A	G	9: 28,813,398	H164R	possibly damaging	Het
Pacrg	A	G	17: 10,403,418	I209T	probably damaging	Het
Pcf11	T	C	7: 92,661,215	M522V	probably benign	Het
Pck1	T	A	2: 173,153,390	M1K	probably null	Het
Pcm1	G	T	8: 41,276,111	E707*	probably null	Het
Pcsk5	G	A	19: 17,654,849	R318W	probably damaging	Het
Phf11d	A	T	14: 59,353,344	M188K	possibly damaging	Het
Ppip5k2	A	T	1: 97,740,537	C615*	probably null	Het
Prkdc	T	A	16: 15,791,927	S3132T	probably damaging	Het
Prl2c5	A	T	13: 13,183,024		probably benign	Het
Prpsap2	A	G	11: 61,741,000	I177T	possibly damaging	Het
Rad50	A	G	11: 53,650,519	S1297P	probably damaging	Het
Rasip1	T	A	7: 45,635,244	N678K	possibly damaging	Het
Rubcn	A	G	16: 32,835,980	S544P	probably damaging	Het
Rwdd2a	A	T	9: 86,574,400	T210S	possibly damaging	Het
Scd2	A	G	19: 44,303,040	D306G	probably damaging	Het
Sema3b	T	C	9: 107,602,918	N207S	probably benign	Het
Sf3b2	C	T	19: 5,274,824	D845N	probably damaging	Het
Sipa1l2	C	A	8: 125,464,410	C947F	probably damaging	Het
Slc18a2	A	T	19: 59,287,367	I461L	probably benign	Het
Slc1a6	C	A	10: 78,801,922	Y427*	probably null	Het
Slc30a4	A	T	2: 122,689,399	I231K	probably damaging	Het
Sos1	G	T	17: 80,453,763	A168D	probably damaging	Het
Sptb	T	C	12: 76,621,371	S651G	probably benign	Het
Stk36	T	C	1: 74,633,620	L1007P	probably damaging	Het
Tek	A	T	4: 94,804,341	N229Y	probably damaging	Het
Tep1	A	G	14: 50,836,768	F1887L	possibly damaging	Het
Tet1	A	T	10: 62,878,209	C602*	probably null	Het
Tnfrsf19	A	G	14: 60,972,036	S262P	possibly damaging	Het
Trim5	T	C	7: 104,265,684	I393V	probably benign	Het
Trpm6	A	G	19: 18,853,587	E1272G	probably benign	Het
Ttc21b	A	T	2: 66,188,326	Y1246N	probably damaging	Het
Ttll3	T	A	6: 113,398,777	L151H	probably damaging	Het
U2surp	C	T	9: 95,484,443	V470I	probably benign	Het
Ubr1	A	T	2: 120,946,657	Y276N	probably benign	Het
Uggt1	A	G	1: 36,179,670	S59P	probably benign	Het
Unc45a	T	C	7: 80,326,344	T796A	probably damaging	Het
Unc5b	C	A	10: 60,778,940	V193F	possibly damaging	Het
Upp1	G	T	11: 9,129,590	M50I	probably benign	Het
Vps18	C	T	2: 119,293,905	R438C	probably damaging	Het
Zfp715	T	C	7: 43,299,336	Y400C	possibly damaging	Het
Zfp955b	T	C	17: 33,302,522	Y322H	probably benign	Het

Other mutations in Slc12a1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00798:Slc12a1	APN	2	125188194	missense	probably damaging	1.00
IGL00845:Slc12a1	APN	2	125188238	missense	probably damaging	1.00
IGL01348:Slc12a1	APN	2	125194131	missense	probably damaging	1.00
IGL01534:Slc12a1	APN	2	125217910	missense	probably damaging	1.00
IGL01677:Slc12a1	APN	2	125178149	splice site	probably benign
IGL02150:Slc12a1	APN	2	125184815	missense	probably damaging	1.00
IGL02220:Slc12a1	APN	2	125188270	critical splice donor site	probably null
IGL02568:Slc12a1	APN	2	125184728	missense	probably damaging	1.00
IGL02602:Slc12a1	APN	2	125154242	missense	probably damaging	1.00
IGL02625:Slc12a1	APN	2	125170691	missense	probably damaging	1.00
IGL02635:Slc12a1	APN	2	125225978	missense	probably benign
IGL02672:Slc12a1	APN	2	125170676	missense	probably damaging	1.00
IGL02718:Slc12a1	APN	2	125161079	nonsense	probably null
IGL03191:Slc12a1	APN	2	125206089	missense	possibly damaging	0.87
FR4449:Slc12a1	UTSW	2	125154216	small insertion	probably benign
FR4548:Slc12a1	UTSW	2	125154214	small insertion	probably benign
FR4737:Slc12a1	UTSW	2	125154214	small insertion	probably benign
PIT4431001:Slc12a1	UTSW	2	125190204	missense	possibly damaging	0.78
R0033:Slc12a1	UTSW	2	125214009	missense	probably benign
R0127:Slc12a1	UTSW	2	125219762	missense	probably damaging	1.00
R0312:Slc12a1	UTSW	2	125226028	missense	probably damaging	0.98
R0692:Slc12a1	UTSW	2	125194162	nonsense	probably null
R1194:Slc12a1	UTSW	2	125184767	missense	probably benign	0.00
R1264:Slc12a1	UTSW	2	125218238	missense	possibly damaging	0.56
R1529:Slc12a1	UTSW	2	125190295	missense	probably damaging	1.00
R1543:Slc12a1	UTSW	2	125184857	missense	possibly damaging	0.93
R1940:Slc12a1	UTSW	2	125194193	missense	probably benign	0.05
R2109:Slc12a1	UTSW	2	125173699	missense	probably damaging	1.00
R2167:Slc12a1	UTSW	2	125173681	missense	probably damaging	1.00
R3409:Slc12a1	UTSW	2	125154151	missense	probably benign	0.00
R3902:Slc12a1	UTSW	2	125188193	missense	probably damaging	1.00
R4079:Slc12a1	UTSW	2	125200623	missense	possibly damaging	0.86
R4502:Slc12a1	UTSW	2	125226044	missense	probably damaging	1.00
R4557:Slc12a1	UTSW	2	125186641	missense	probably damaging	1.00
R4719:Slc12a1	UTSW	2	125153993	missense	possibly damaging	0.82
R4782:Slc12a1	UTSW	2	125161079	nonsense	probably null
R4845:Slc12a1	UTSW	2	125188226	missense	probably damaging	1.00
R4913:Slc12a1	UTSW	2	125228750	missense	probably damaging	0.96
R5024:Slc12a1	UTSW	2	125166137	missense	probably benign	0.00
R5112:Slc12a1	UTSW	2	125218224	missense	possibly damaging	0.63
R5334:Slc12a1	UTSW	2	125217889	missense	probably damaging	1.00
R5470:Slc12a1	UTSW	2	125170714	missense	probably damaging	1.00
R6057:Slc12a1	UTSW	2	125190213	missense	probably damaging	1.00
R6604:Slc12a1	UTSW	2	125184815	missense	probably damaging	1.00
R6941:Slc12a1	UTSW	2	125214079	missense	possibly damaging	0.85
R6944:Slc12a1	UTSW	2	125160534	missense	probably damaging	0.97
R7049:Slc12a1	UTSW	2	125171257	missense	probably benign	0.04
R7204:Slc12a1	UTSW	2	125200622	missense	possibly damaging	0.93
R7427:Slc12a1	UTSW	2	125214132	missense	probably benign
R7428:Slc12a1	UTSW	2	125214132	missense	probably benign
R7432:Slc12a1	UTSW	2	125206040	missense	probably benign	0.36
R7470:Slc12a1	UTSW	2	125217895	nonsense	probably null
R7828:Slc12a1	UTSW	2	125166682	missense	possibly damaging	0.85
R7862:Slc12a1	UTSW	2	125161094	missense	probably damaging	0.99
R7923:Slc12a1	UTSW	2	125214092	missense	possibly damaging	0.75
R8020:Slc12a1	UTSW	2	125178102	missense	possibly damaging	0.78
R8071:Slc12a1	UTSW	2	125186314	missense	probably damaging	1.00
R8272:Slc12a1	UTSW	2	125228816	missense	probably damaging	1.00
R8302:Slc12a1	UTSW	2	125190289	missense	probably damaging	0.99
R8722:Slc12a1	UTSW	2	125160598	missense	probably damaging	1.00
R9029:Slc12a1	UTSW	2	125154084	missense	probably benign
R9449:Slc12a1	UTSW	2	125186224	missense	probably damaging	1.00
RF032:Slc12a1	UTSW	2	125154210	small insertion	probably benign

Predicted Primers

PCR Primer
(F):5'- TCAGCTCTGATTCCATGCATCTGTG -3'
(R):5'- GCCTGAACAATAAGACCTGGGGAC -3'

Sequencing Primer
(F):5'- CCATGCATCTGTGAAATAATGAGTCC -3'
(R):5'- CTCAGGACATCTGATGAGCTATC -3'

Posted On

2013-04-24