Mutagenetix > Incidental Mutation

Incidental Mutation 'R7395:Slc12a6'

573707

Institutional Source

Beutler Lab

Gene Symbol

Slc12a6

Ensembl Gene

ENSMUSG00000027130

Gene Name

solute carrier family 12, member 6

Synonyms

KCC3, gaxp

MMRRC Submission

045477-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.212) question?

Stock #

R7395 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

112096659-112193508 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 112182887 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Isoleucine at position 754 (N754I)

Ref Sequence

ENSEMBL: ENSMUSP00000028549 (fasta)

Gene Model

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

AlphaFold

Q924N4

Predicted Effect

probably damaging
Transcript: ENSMUST00000028549
AA Change: N754I

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

SMART Domains

Protein: ENSMUSP00000028549
Gene: ENSMUSG00000027130
AA Change: N754I

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: N703I

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000051490
Gene: ENSMUSG00000027130
AA Change: N703I

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: N739I

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000106615
Gene: ENSMUSG00000027130
AA Change: N739I

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: N754I

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000106619
Gene: ENSMUSG00000027130
AA Change: N754I

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

probably damaging
Transcript: ENSMUST00000141047
AA Change: N739I

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

SMART Domains

Protein: ENSMUSP00000124314
Gene: ENSMUSG00000096764
AA Change: N739I

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

99% (92/93)

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: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3830403N18Rik	G	T	X: 55,184,140 (GRCm39)		probably null	Het
4930433I11Rik	A	T	7: 40,639,102 (GRCm39)	T13S	probably damaging	Het
Abca13	A	G	11: 9,241,658 (GRCm39)	I1174V	probably benign	Het
Acoxl	G	A	2: 127,726,336 (GRCm39)	V237M	probably damaging	Het
Adam33	A	C	2: 130,903,089 (GRCm39)	W52G	probably benign	Het
Adgrv1	T	C	13: 81,707,467 (GRCm39)	H1313R	probably damaging	Het
Ap3d1	T	C	10: 80,566,716 (GRCm39)	T89A	probably benign	Het
Armc8	T	C	9: 99,415,185 (GRCm39)	E165G	probably damaging	Het
Atp6v1c1	T	C	15: 38,691,949 (GRCm39)	*383Q	probably null	Het
Atp8b4	A	T	2: 126,217,614 (GRCm39)	L634Q	possibly damaging	Het
B3glct	A	G	5: 149,649,069 (GRCm39)		probably null	Het
Bhlhe40	TG	TGG	6: 108,641,818 (GRCm39)	254	probably null	Het
Bicd2	A	G	13: 49,531,706 (GRCm39)	D316G	possibly damaging	Het
Bop1	A	T	15: 76,338,041 (GRCm39)	S610T	probably damaging	Het
Car11	T	A	7: 45,350,745 (GRCm39)	Y80*	probably null	Het
Ccdc121rt2	A	T	5: 112,598,035 (GRCm39)	E194V	possibly damaging	Het
Ccdc96	T	C	5: 36,642,609 (GRCm39)	I205T	probably benign	Het
Ces2a	A	G	8: 105,466,273 (GRCm39)	E390G	probably benign	Het
Cfap54	C	A	10: 92,720,565 (GRCm39)	V2630L	unknown	Het
Chek2	G	T	5: 111,019,974 (GRCm39)		probably null	Het
Cntn3	C	T	6: 102,314,355 (GRCm39)		probably null	Het
Cpne3	A	T	4: 19,528,239 (GRCm39)	D339E	probably damaging	Het
Crocc2	C	T	1: 93,143,829 (GRCm39)	Q1403*	probably null	Het
Crppa	A	T	12: 36,551,994 (GRCm39)	I283F	possibly damaging	Het
Csnka2ip	G	A	16: 64,299,803 (GRCm39)	T187I		Het
Ctu1	A	G	7: 43,326,019 (GRCm39)	H226R	possibly damaging	Het
Cubn	G	T	2: 13,291,875 (GRCm39)	Q3317K	probably damaging	Het
Cyp17a1	A	G	19: 46,659,134 (GRCm39)	L169P	probably benign	Het
Dcc	T	A	18: 71,507,640 (GRCm39)	K911*	probably null	Het
Dcun1d2	G	A	8: 13,328,675 (GRCm39)	R75*	probably null	Het
Defb19	A	T	2: 152,421,943 (GRCm39)		probably null	Het
Dffb	A	T	4: 154,053,570 (GRCm39)	S257R	probably damaging	Het
Dip2c	A	C	13: 9,664,413 (GRCm39)	N942T	probably damaging	Het
Dnah3	T	A	7: 119,565,474 (GRCm39)	I169F		Het
Dnah3	T	C	7: 119,660,183 (GRCm39)	M830V	probably benign	Het
Dnajc5g	G	A	5: 31,269,009 (GRCm39)	S130N	possibly damaging	Het
Dscaml1	C	A	9: 45,613,703 (GRCm39)	Q939K	possibly damaging	Het
Evpl	G	C	11: 116,117,905 (GRCm39)	N761K	possibly damaging	Het
Fbxw8	A	T	5: 118,206,280 (GRCm39)	I556N	probably damaging	Het
Fry	G	T	5: 150,304,348 (GRCm39)	M579I	possibly damaging	Het
Ggt7	A	T	2: 155,337,800 (GRCm39)	M488K	probably benign	Het
Gnpnat1	T	A	14: 45,619,038 (GRCm39)	H107L	probably benign	Het
Golga2	C	A	2: 32,195,599 (GRCm39)	P798Q	possibly damaging	Het
Gpr35	G	A	1: 92,910,929 (GRCm39)	A214T	probably damaging	Het
Greb1	A	T	12: 16,759,431 (GRCm39)		probably null	Het
Hdac10	G	A	15: 89,012,487 (GRCm39)	T32I	probably benign	Het
Hkdc1	G	A	10: 62,221,478 (GRCm39)	T860I	probably damaging	Het
Icam5	C	A	9: 20,946,738 (GRCm39)	P422Q	possibly damaging	Het
Ist1	A	C	8: 110,404,159 (GRCm39)	S238A	probably benign	Het
Lrig2	T	C	3: 104,404,836 (GRCm39)	N91D	probably benign	Het
Mapt	A	C	11: 104,218,949 (GRCm39)	D352A	probably damaging	Het
Micall2	G	A	5: 139,702,124 (GRCm39)	P373L	possibly damaging	Het
Mocs1	A	G	17: 49,761,585 (GRCm39)	S560G	possibly damaging	Het
Mpo	A	G	11: 87,691,950 (GRCm39)	D461G	probably damaging	Het
Myo1a	G	T	10: 127,546,309 (GRCm39)	V271L	probably damaging	Het
Ncoa1	G	A	12: 4,345,188 (GRCm39)	P720S	not run	Het
Ncr1	T	A	7: 4,341,150 (GRCm39)	I47N	probably damaging	Het
Ndufb6	G	A	4: 40,277,730 (GRCm39)	R66C	probably damaging	Het
Obox5	A	T	7: 15,492,668 (GRCm39)	S208C	probably damaging	Het
Or10q1	T	C	19: 13,726,502 (GRCm39)	S11P	probably damaging	Het
Or2n1d	A	T	17: 38,646,755 (GRCm39)	K236*	probably null	Het
Or5p75-ps1	T	A	7: 108,107,611 (GRCm39)	F116Y	unknown	Het
Or7d9	T	A	9: 20,197,826 (GRCm39)	M285K	probably damaging	Het
Padi4	A	C	4: 140,488,983 (GRCm39)	V152G	probably damaging	Het
Pdzd7	A	T	19: 45,025,450 (GRCm39)	D348E	probably damaging	Het
Pdzph1	T	A	17: 59,186,154 (GRCm39)	K1212N	possibly damaging	Het
Piezo2	C	T	18: 63,160,634 (GRCm39)	G2341R	probably damaging	Het
Plb1	A	G	5: 32,511,028 (GRCm39)	K1298E	probably benign	Het
Prr14l	A	G	5: 32,985,982 (GRCm39)	L1171P	probably benign	Het
Rab11fip5	T	C	6: 85,318,850 (GRCm39)	T680A	probably benign	Het
Rev1	A	T	1: 38,127,146 (GRCm39)	N371K	possibly damaging	Het
Rsf1	CGGCGGCGG	CGGCGGCGGGGGCGGCGG	7: 97,229,133 (GRCm39)		probably benign	Het
Ryr2	A	G	13: 11,799,997 (GRCm39)	C917R	probably damaging	Het
Sall1	A	T	8: 89,757,549 (GRCm39)	S852T	possibly damaging	Het
Serpine2	A	G	1: 79,779,272 (GRCm39)	F296L	probably damaging	Het
Slc39a6	A	T	18: 24,718,332 (GRCm39)	L575Q	probably damaging	Het
Smarcc2	T	A	10: 128,321,475 (GRCm39)	L890Q	probably damaging	Het
Smg5	T	A	3: 88,268,378 (GRCm39)	V1006D	probably damaging	Het
Ssh2	T	C	11: 77,283,899 (GRCm39)	V51A	probably damaging	Het
St14	T	C	9: 31,008,195 (GRCm39)	K547E	probably benign	Het
Stag1	T	G	9: 100,678,781 (GRCm39)	V234G	probably damaging	Het
Stag3	A	T	5: 138,280,207 (GRCm39)	Q24L	probably benign	Het
Stra6	T	C	9: 58,048,380 (GRCm39)	Y158H	probably damaging	Het
Tcstv1a	A	T	13: 120,355,666 (GRCm39)		probably null	Het
Tmem196	G	A	12: 119,975,002 (GRCm39)	C62Y	probably damaging	Het
Tmem265	T	A	7: 127,164,039 (GRCm39)	F84L		Het
Tph1	C	T	7: 46,306,627 (GRCm39)		probably null	Het
Ttn	A	G	2: 76,776,834 (GRCm39)	I1522T	unknown	Het
Ulk4	T	A	9: 121,084,178 (GRCm39)	Q129L	probably benign	Het
Usp17la	T	A	7: 104,510,792 (GRCm39)	S466T	probably benign	Het
Vmn2r31	A	T	7: 7,387,744 (GRCm39)	V609E	probably damaging	Het
Vmn2r52	C	T	7: 9,904,744 (GRCm39)	C365Y	probably benign	Het
Zbtb4	A	T	11: 69,666,937 (GRCm39)	T81S	possibly damaging	Het
Zfp605	A	T	5: 110,259,885 (GRCm39)		probably benign	Het

Other mutations in Slc12a6

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01488:Slc12a6	APN	2	112,183,409 (GRCm39)	splice site	probably null
IGL02573:Slc12a6	APN	2	112,188,986 (GRCm39)	critical splice donor site	probably null
burgess	UTSW	2	112,177,662 (GRCm39)	missense	probably benign	0.09
petrified_forest	UTSW	2	112,177,771 (GRCm39)	missense	probably damaging	1.00
Prebiotic	UTSW	2	112,183,280 (GRCm39)	missense	probably benign	0.30
R0548:Slc12a6	UTSW	2	112,166,269 (GRCm39)	critical splice donor site	probably null
R1495:Slc12a6	UTSW	2	112,184,535 (GRCm39)	missense	probably damaging	0.99
R1726:Slc12a6	UTSW	2	112,177,771 (GRCm39)	missense	probably damaging	1.00
R1856:Slc12a6	UTSW	2	112,166,272 (GRCm39)	splice site	probably null
R1958:Slc12a6	UTSW	2	112,185,503 (GRCm39)	missense	possibly damaging	0.92
R2112:Slc12a6	UTSW	2	112,186,830 (GRCm39)	missense	probably damaging	1.00
R2865:Slc12a6	UTSW	2	112,177,662 (GRCm39)	missense	probably benign	0.09
R3888:Slc12a6	UTSW	2	112,097,375 (GRCm39)	missense	possibly damaging	0.76
R4412:Slc12a6	UTSW	2	112,166,233 (GRCm39)	missense	possibly damaging	0.95
R4655:Slc12a6	UTSW	2	112,188,111 (GRCm39)	critical splice acceptor site	probably null
R4669:Slc12a6	UTSW	2	112,184,640 (GRCm39)	missense	probably damaging	1.00
R4928:Slc12a6	UTSW	2	112,183,306 (GRCm39)	missense	probably damaging	1.00
R4974:Slc12a6	UTSW	2	112,188,870 (GRCm39)	missense	probably damaging	1.00
R5016:Slc12a6	UTSW	2	112,186,972 (GRCm39)	intron	probably benign
R5372:Slc12a6	UTSW	2	112,177,705 (GRCm39)	nonsense	probably null
R5405:Slc12a6	UTSW	2	112,169,724 (GRCm39)	missense	probably damaging	1.00
R5786:Slc12a6	UTSW	2	112,115,067 (GRCm39)	missense	probably benign	0.01
R5836:Slc12a6	UTSW	2	112,172,343 (GRCm39)	missense	possibly damaging	0.62
R6280:Slc12a6	UTSW	2	112,167,703 (GRCm39)	missense	probably damaging	1.00
R6310:Slc12a6	UTSW	2	112,166,184 (GRCm39)	missense	probably damaging	1.00
R6525:Slc12a6	UTSW	2	112,182,796 (GRCm39)	missense	probably damaging	1.00
R6597:Slc12a6	UTSW	2	112,183,280 (GRCm39)	missense	probably damaging	1.00
R6723:Slc12a6	UTSW	2	112,168,287 (GRCm39)	missense	probably damaging	1.00
R6895:Slc12a6	UTSW	2	112,185,440 (GRCm39)	missense	probably damaging	1.00
R7059:Slc12a6	UTSW	2	112,183,257 (GRCm39)	missense	probably damaging	0.99
R7188:Slc12a6	UTSW	2	112,164,760 (GRCm39)	missense	probably benign	0.04
R7552:Slc12a6	UTSW	2	112,172,319 (GRCm39)	missense	probably damaging	1.00
R7992:Slc12a6	UTSW	2	112,166,256 (GRCm39)	missense	probably damaging	1.00
R8016:Slc12a6	UTSW	2	112,186,899 (GRCm39)	missense	probably benign	0.42
R8122:Slc12a6	UTSW	2	112,097,167 (GRCm39)	start codon destroyed	probably null
R8192:Slc12a6	UTSW	2	112,181,722 (GRCm39)	missense	probably damaging	1.00
R8222:Slc12a6	UTSW	2	112,169,870 (GRCm39)	splice site	probably null
R8534:Slc12a6	UTSW	2	112,174,312 (GRCm39)	missense	probably damaging	1.00
R9018:Slc12a6	UTSW	2	112,174,585 (GRCm39)	splice site	probably benign
R9281:Slc12a6	UTSW	2	112,164,754 (GRCm39)	missense	probably benign	0.00
R9418:Slc12a6	UTSW	2	112,174,555 (GRCm39)	missense
R9448:Slc12a6	UTSW	2	112,179,704 (GRCm39)	missense	probably damaging	1.00
R9460:Slc12a6	UTSW	2	112,183,280 (GRCm39)	missense	probably benign	0.30
R9694:Slc12a6	UTSW	2	112,174,881 (GRCm39)	missense	probably damaging	1.00
R9712:Slc12a6	UTSW	2	112,186,817 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGCTAGATTTAGAGAATCCTGGG -3'
(R):5'- AGGAGGGCCACAAAGCATTC -3'

Sequencing Primer
(F):5'- TTTTTCTCCCAAGGGCTG -3'
(R):5'- GCATTCAACTTTGACAGAAGAATGG -3'

Posted On

2019-09-13