Mutagenetix > Incidental Mutations

Incidental Mutation 'R4669:Slc12a6'

352228

Institutional Source

Beutler Lab

Gene Symbol

Slc12a6

Ensembl Gene

ENSMUSG00000027130

Gene Name

solute carrier family 12, member 6

Synonyms

gaxp, KCC3

MMRRC Submission

041925-MU

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.288) question?

Stock #

R4669 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

112265825-112363163 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 112354295 bp

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 853 (H853R)

Ref Sequence

ENSEMBL: ENSMUSP00000028549 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028549] [ENSMUST00000053666] [ENSMUST00000110987] [ENSMUST00000110991] [ENSMUST00000141047]

Predicted Effect

probably damaging
Transcript: ENSMUST00000028549
AA Change: H853R

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000028549
Gene: ENSMUSG00000027130
AA Change: H853R

Domain	Start	End	E-Value	Type
low complexity region	28	53	N/A	INTRINSIC
SCOP:d1qqea_	114	171	8e-3	SMART
Pfam:AA_permease	190	384	4.1e-25	PFAM
Pfam:AA_permease	453	761	2.3e-43	PFAM
Pfam:SLC12	773	897	7.1e-20	PFAM
Pfam:SLC12	892	1150	3.9e-32	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000053666
AA Change: H802R

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000051490
Gene: ENSMUSG00000027130
AA Change: H802R

Domain	Start	End	E-Value	Type
Pfam:AA_permease	139	333	2.3e-25	PFAM
Pfam:AA_permease_2	385	668	1.5e-19	PFAM
Pfam:AA_permease	391	710	4.5e-41	PFAM
low complexity region	828	842	N/A	INTRINSIC
Pfam:KCl_Cotrans_1	967	996	2.2e-23	PFAM
low complexity region	1079	1091	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000110987
AA Change: H838R

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000106615
Gene: ENSMUSG00000027130
AA Change: H838R

Domain	Start	End	E-Value	Type
low complexity region	28	53	N/A	INTRINSIC
SCOP:d1qqea_	99	156	4e-3	SMART
Pfam:AA_permease	175	369	3.9e-25	PFAM
Pfam:AA_permease_2	421	704	3.2e-19	PFAM
Pfam:AA_permease	426	746	5.8e-41	PFAM
low complexity region	864	878	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000110991
AA Change: H853R

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000106619
Gene: ENSMUSG00000027130
AA Change: H853R

Domain	Start	End	E-Value	Type
low complexity region	28	53	N/A	INTRINSIC
SCOP:d1qqea_	114	171	7e-3	SMART
Pfam:AA_permease	190	384	4.2e-25	PFAM
Pfam:AA_permease_2	436	719	2.9e-19	PFAM
Pfam:AA_permease	442	761	8.2e-41	PFAM
low complexity region	879	893	N/A	INTRINSIC
Pfam:KCl_Cotrans_1	1018	1047	2.7e-23	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132752

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133840

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137896

Predicted Effect

probably damaging
Transcript: ENSMUST00000141047
AA Change: H838R

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000124314
Gene: ENSMUSG00000096764
AA Change: H838R

Domain	Start	End	E-Value	Type
low complexity region	28	53	N/A	INTRINSIC
SCOP:d1qqea_	99	156	8e-3	SMART
Pfam:AA_permease	175	369	6.6e-25	PFAM
Pfam:AA_permease	438	746	3.6e-43	PFAM
Pfam:SLC12	758	884	6.8e-20	PFAM
Pfam:SLC12	877	1033	5.9e-20	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000156470

Coding Region Coverage

1x: 99.2%
3x: 98.6%
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 is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations exhibit locomotor deficits, progressive neurodegeneration, slow progressive deafness and failure to breed. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acad8	A	G	9: 26,990,627	L147P	probably damaging	Het
Acan	A	G	7: 79,101,142	E464G	probably benign	Het
Agap1	A	G	1: 89,837,806		probably null	Het
Akap13	A	G	7: 75,729,094	T2128A	probably damaging	Het
Ap2a1	A	T	7: 44,902,919		probably benign	Het
Arap3	T	C	18: 37,996,254	D217G	probably benign	Het
Arl2	C	A	19: 6,134,686	R179L	probably damaging	Het
Atg2a	T	A	19: 6,258,987		probably null	Het
B3gat1	T	A	9: 26,751,756	L6Q	probably benign	Het
Bcl10	A	G	3: 145,930,572	N75S	probably damaging	Het
Bmpr2	T	C	1: 59,867,716	L656S	probably damaging	Het
Brms1l	A	G	12: 55,841,571	E48G	possibly damaging	Het
C2cd2l	A	T	9: 44,315,025	N414K	possibly damaging	Het
Capn2	C	T	1: 182,470,780	C640Y	probably benign	Het
Ccdc153	G	T	9: 44,245,724	R99M	probably damaging	Het
Ccdc51	A	G	9: 109,090,962	N142S	probably benign	Het
Ccdc58	A	G	16: 36,082,719	D27G	probably damaging	Het
Cdipt	A	G	7: 126,978,406	H108R	possibly damaging	Het
Ceacam20	T	C	7: 19,986,027	Y495H	probably damaging	Het
Celf2	T	C	2: 6,721,528	I47V	probably benign	Het
Cts3	C	T	13: 61,566,823	E223K	probably benign	Het
Cyp2a22	T	C	7: 26,937,855	D168G	possibly damaging	Het
Cyp2c67	T	A	19: 39,643,654	H90L	probably benign	Het
Ddx4	T	C	13: 112,622,244	Y261C	probably damaging	Het
Dnah17	T	C	11: 118,074,293	T2308A	probably benign	Het
Dnah6	T	C	6: 73,037,688	T3587A	probably damaging	Het
Dpy19l1	C	T	9: 24,432,368	V494I	possibly damaging	Het
Dse	T	G	10: 34,153,012	Y694S	probably damaging	Het
Emilin3	T	C	2: 160,910,797	I78V	probably benign	Het
Esam	T	A	9: 37,536,656	Y195*	probably null	Het
Extl3	T	A	14: 65,076,296	N479I	possibly damaging	Het
Fat2	A	G	11: 55,311,615	V211A	probably benign	Het
Ganc	G	T	2: 120,431,067	V343F	probably benign	Het
Ggt5	T	C	10: 75,603,031	L121P	probably damaging	Het
Gnmt	A	T	17: 46,726,299	C186*	probably null	Het
Gpr75	A	T	11: 30,892,072	I326F	probably damaging	Het
Gsdme	C	T	6: 50,208,122	V451M	probably damaging	Het
H2-T23	G	T	17: 36,031,798	D149E	probably damaging	Het
Hmcn2	G	T	2: 31,435,792	R4277L	probably benign	Het
Irf9	C	A	14: 55,605,766	H94N	probably benign	Het
Jhy	T	C	9: 40,961,153	N20S	probably benign	Het
Klf17	C	A	4: 117,760,371	C263F	probably damaging	Het
Lama5	T	C	2: 180,180,637	Y2881C	probably damaging	Het
Lig1	T	G	7: 13,311,028	I882S	probably damaging	Het
Ltn1	A	T	16: 87,418,487	M420K	possibly damaging	Het
Mael	T	C	1: 166,235,508	E125G	probably damaging	Het
Mib2	C	T	4: 155,657,415	D275N	possibly damaging	Het
Mical3	C	T	6: 120,957,703	R1805Q	probably damaging	Het
Mllt10	A	G	2: 18,203,633	D158G	probably damaging	Het
Mocs1	A	G	17: 49,454,585	D569G	possibly damaging	Het
Msh6	T	C	17: 87,984,806	S330P	possibly damaging	Het
Mtmr2	T	C	9: 13,795,964	S199P	probably damaging	Het
Ndufaf5	T	C	2: 140,187,755	V164A	probably benign	Het
Nek9	T	C	12: 85,314,204	E518G	probably benign	Het
Nfatc2	T	C	2: 168,571,490	I72V	probably benign	Het
Nlrp9c	C	T	7: 26,375,368	A746T	possibly damaging	Het
Nupl2	A	G	5: 24,182,417	R402G	probably benign	Het
Ogdh	G	T	11: 6,340,600	C406F	probably benign	Het
Olfr1045	A	T	2: 86,197,933	M273K	possibly damaging	Het
Olfr1225	G	A	2: 89,170,901	H104Y	probably damaging	Het
Olfr146	T	A	9: 39,019,379	Y54F	probably benign	Het
Olfr411	A	G	11: 74,346,963	V207A	probably benign	Het
Olfr881	A	T	9: 37,993,085	I198F	possibly damaging	Het
Otof	A	G	5: 30,420,974		probably null	Het
Pcdhb17	T	C	18: 37,486,206	S350P	probably damaging	Het
Phf3	T	C	1: 30,829,946	T674A	probably damaging	Het
Pikfyve	T	A	1: 65,250,273	C1235S	probably damaging	Het
Ppfia3	T	C	7: 45,352,093	E465G	probably damaging	Het
Prkg1	T	A	19: 31,664,239	I15F	probably damaging	Het
Rab5c	A	G	11: 100,720,017	F22L	probably damaging	Het
Raf1	A	G	6: 115,632,919	S220P	probably damaging	Het
Rgl1	T	G	1: 152,521,371	R716S	probably damaging	Het
Rhbg	C	A	3: 88,245,966	W205L	probably damaging	Het
Rimbp3	A	G	16: 17,209,189	E159G	possibly damaging	Het
Ryr1	T	C	7: 29,059,831	D3338G	probably null	Het
Sash1	T	C	10: 8,730,385	N747S	probably benign	Het
Serpina3g	A	T	12: 104,239,220	I73F	probably damaging	Het
Sfxn2	C	A	19: 46,585,774	N134K	probably damaging	Het
Slc16a12	C	T	19: 34,672,565	D357N	probably damaging	Het
Slc39a8	T	C	3: 135,856,011	Y164H	probably benign	Het
Snx9	A	G	17: 5,927,224	K518E	probably damaging	Het
Spdye4c	G	A	2: 128,592,353	V5I	possibly damaging	Het
Spef2	A	G	15: 9,676,373	V704A	probably benign	Het
Stard3nl	T	A	13: 19,376,519	N29Y	probably damaging	Het
Strap	C	A	6: 137,735,386	S11*	probably null	Het
Synpo2	A	G	3: 123,113,063	L868P	probably damaging	Het
Tenm2	A	G	11: 36,010,487	V2474A	probably damaging	Het
Tm9sf4	T	A	2: 153,187,308	V92D	probably damaging	Het
Tmf1	A	T	6: 97,170,427	M526K	probably benign	Het
Top2b	T	G	14: 16,409,189	I777M	probably damaging	Het
Ttc39d	A	G	17: 80,217,639	I576V	probably benign	Het
Upk1a	T	G	7: 30,605,129	T193P	probably benign	Het
Vmn2r67	A	T	7: 85,150,524	V502E	probably benign	Het
Wdr17	A	G	8: 54,690,048	V189A	possibly damaging	Het
Wrap73	A	T	4: 154,151,696	S161C	probably benign	Het
Zfp568	A	G	7: 30,023,277	H549R	probably damaging	Het
Zfp605	T	A	5: 110,127,361	M115K	possibly damaging	Het
Zp1	T	A	19: 10,918,905	H152L	probably benign	Het

Other mutations in Slc12a6

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01488:Slc12a6	APN	2	112353064	splice site	probably null
IGL02573:Slc12a6	APN	2	112358641	critical splice donor site	probably null
R0548:Slc12a6	UTSW	2	112335924	critical splice donor site	probably null
R1495:Slc12a6	UTSW	2	112354190	missense	probably damaging	0.99
R1726:Slc12a6	UTSW	2	112347426	missense	probably damaging	1.00
R1856:Slc12a6	UTSW	2	112335927	splice site	probably null
R1958:Slc12a6	UTSW	2	112355158	missense	possibly damaging	0.92
R2112:Slc12a6	UTSW	2	112356485	missense	probably damaging	1.00
R2865:Slc12a6	UTSW	2	112347317	missense	probably benign	0.09
R3888:Slc12a6	UTSW	2	112267030	missense	possibly damaging	0.76
R4412:Slc12a6	UTSW	2	112335888	missense	possibly damaging	0.95
R4655:Slc12a6	UTSW	2	112357766	critical splice acceptor site	probably null
R4928:Slc12a6	UTSW	2	112352961	missense	probably damaging	1.00
R4974:Slc12a6	UTSW	2	112358525	missense	probably damaging	1.00
R5016:Slc12a6	UTSW	2	112356627	intron	probably benign
R5372:Slc12a6	UTSW	2	112347360	nonsense	probably null
R5405:Slc12a6	UTSW	2	112339379	missense	probably damaging	1.00
R5786:Slc12a6	UTSW	2	112284722	missense	probably benign	0.01
R5836:Slc12a6	UTSW	2	112341998	missense	possibly damaging	0.62
R6280:Slc12a6	UTSW	2	112337358	missense	probably damaging	1.00
R6310:Slc12a6	UTSW	2	112335839	missense	probably damaging	1.00
R6525:Slc12a6	UTSW	2	112352451	missense	probably damaging	1.00
R6597:Slc12a6	UTSW	2	112352935	missense	probably damaging	1.00
R6723:Slc12a6	UTSW	2	112337942	missense	probably damaging	1.00
R6895:Slc12a6	UTSW	2	112355095	missense	probably damaging	1.00
R7059:Slc12a6	UTSW	2	112352912	missense	probably damaging	0.99
R7188:Slc12a6	UTSW	2	112334415	missense	probably benign	0.04
R7395:Slc12a6	UTSW	2	112352542	missense	probably damaging	1.00
R7552:Slc12a6	UTSW	2	112341974	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGGAGCTACATGTGGACAGC -3'
(R):5'- ATGTTTCATGGCATGGTCTCTAC -3'

Sequencing Primer
(F):5'- TAATCTTATGTAGAATCTGGGGAGAG -3'
(R):5'- CATGGTCTCTACTTTAGGACAGAG -3'

Posted On

2015-10-08