Mutagenetix > Incidental Mutation

Incidental Mutation 'R7552:Slc12a6'

584450

Institutional Source

Beutler Lab

Gene Symbol

Slc12a6

Ensembl Gene

ENSMUSG00000027130

Gene Name

solute carrier family 12, member 6

Synonyms

KCC3, gaxp

MMRRC Submission

045621-MU

Accession Numbers

Essential gene?

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

Stock #

R7552 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

112096659-112193508 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 112172319 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 421 (D421G)

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: D421G

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000028549
Gene: ENSMUSG00000027130
AA Change: D421G

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

possibly damaging
Transcript: ENSMUST00000053666
AA Change: D370G

PolyPhen 2 Score 0.952 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000051490
Gene: ENSMUSG00000027130
AA Change: D370G

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

possibly damaging
Transcript: ENSMUST00000110987
AA Change: D406G

PolyPhen 2 Score 0.917 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000106615
Gene: ENSMUSG00000027130
AA Change: D406G

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: D421G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000106619
Gene: ENSMUSG00000027130
AA Change: D421G

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: D406G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000124314
Gene: ENSMUSG00000096764
AA Change: D406G

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: 99.7%
20x: 99.0%

Validation Efficiency

100% (89/89)

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abhd17a	A	G	10: 80,419,737 (GRCm39)	Y290H	probably benign	Het
Aco2	T	C	15: 81,788,142 (GRCm39)	V257A	probably damaging	Het
Adam26a	C	A	8: 44,023,007 (GRCm39)	C161F	possibly damaging	Het
Adam9	G	A	8: 25,445,988 (GRCm39)	P820S	unknown	Het
Adcy4	G	A	14: 56,010,922 (GRCm39)	T665M	probably benign	Het
Ahnak	T	A	19: 8,984,188 (GRCm39)	M1824K	probably benign	Het
Alpi	T	C	1: 87,026,795 (GRCm39)	N428D	probably benign	Het
Ano5	C	T	7: 51,196,528 (GRCm39)	P153L	probably benign	Het
Atp1a1	A	T	3: 101,489,437 (GRCm39)	L725*	probably null	Het
Atp8b2	G	A	3: 89,854,071 (GRCm39)	T595I	probably damaging	Het
Ccdc66	T	C	14: 27,220,820 (GRCm39)	I35V	possibly damaging	Het
Cd163	A	G	6: 124,284,187 (GRCm39)	T120A	probably benign	Het
Cmah	A	T	13: 24,640,938 (GRCm39)	T396S	possibly damaging	Het
Cmya5	C	T	13: 93,205,820 (GRCm39)	V3350I	probably benign	Het
Commd9	A	C	2: 101,731,410 (GRCm39)	K198N	probably damaging	Het
Cxcr1	A	G	1: 74,231,773 (GRCm39)	V83A	probably benign	Het
D630045J12Rik	A	G	6: 38,125,383 (GRCm39)	S1544P	probably damaging	Het
Ddt	A	T	10: 75,609,048 (GRCm39)		probably null	Het
Depdc7	A	G	2: 104,557,585 (GRCm39)	S222P	possibly damaging	Het
Ehd2	A	G	7: 15,684,431 (GRCm39)	I456T	probably damaging	Het
Epas1	A	T	17: 87,136,471 (GRCm39)	M748L	probably benign	Het
Esr1	G	A	10: 4,806,903 (GRCm39)	R273H	probably damaging	Het
Fras1	G	A	5: 96,916,297 (GRCm39)	D3444N	probably damaging	Het
Hand2	A	G	8: 57,775,272 (GRCm39)	R111G	probably damaging	Het
Hecw1	A	T	13: 14,490,835 (GRCm39)	V306E	probably damaging	Het
Ift140	T	C	17: 25,252,089 (GRCm39)	I312T	probably benign	Het
Ikbke	A	T	1: 131,199,887 (GRCm39)	L257*	probably null	Het
Kcnk5	G	A	14: 20,192,349 (GRCm39)	P271S	probably benign	Het
Lama1	T	C	17: 68,044,662 (GRCm39)	V187A		Het
Lemd2	A	T	17: 27,412,810 (GRCm39)		probably null	Het
Lig3	T	A	11: 82,679,717 (GRCm39)	D341E	probably benign	Het
Lpcat1	C	T	13: 73,643,014 (GRCm39)	S196L	probably damaging	Het
Lrp1b	A	T	2: 40,567,582 (GRCm39)	D4048E		Het
Lrrfip1	G	A	1: 91,033,005 (GRCm39)	E158K	probably damaging	Het
Mcm5	T	C	8: 75,848,220 (GRCm39)	S490P	probably damaging	Het
Mia3	A	C	1: 183,147,036 (GRCm39)	Y73*	probably null	Het
Minar1	T	A	9: 89,483,888 (GRCm39)	H503L	probably benign	Het
Msr1	A	T	8: 40,077,003 (GRCm39)	N202K	probably benign	Het
N4bp2l2	A	T	5: 150,585,286 (GRCm39)	Y231*	probably null	Het
Nbeal2	A	G	9: 110,482,985 (GRCm39)	W11R	probably benign	Het
Ncor1	T	C	11: 62,264,250 (GRCm39)	E384G	possibly damaging	Het
Neb	A	G	2: 52,137,202 (GRCm39)	V254A		Het
Nlrp9b	T	C	7: 19,779,691 (GRCm39)	S785P	probably benign	Het
Oprd1	T	G	4: 131,841,092 (GRCm39)	I289L	possibly damaging	Het
Or4c10	G	T	2: 89,761,064 (GRCm39)	D304Y	probably benign	Het
Or4s2	A	G	2: 88,473,752 (GRCm39)	I214V	probably benign	Het
Or5m12	A	G	2: 85,734,447 (GRCm39)	V317A	probably benign	Het
Or6a2	T	C	7: 106,600,534 (GRCm39)	T178A	probably benign	Het
Or6c2	T	A	10: 129,362,429 (GRCm39)	F111Y	possibly damaging	Het
Orc1	A	G	4: 108,445,951 (GRCm39)	N23S	probably benign	Het
Paip1	A	T	13: 119,577,356 (GRCm39)	H149L	possibly damaging	Het
Pdhx	A	T	2: 102,877,099 (GRCm39)	D103E	probably benign	Het
Pi4ka	T	C	16: 17,109,080 (GRCm39)	Y1614C		Het
Pias3	ACC	AC	3: 96,608,701 (GRCm39)		probably null	Het
Pigb	A	G	9: 72,941,770 (GRCm39)	V163A	probably benign	Het
Pla2g4d	A	G	2: 120,114,620 (GRCm39)	I37T	possibly damaging	Het
Ppfia1	A	T	7: 144,059,982 (GRCm39)	V610D	probably damaging	Het
Pramel41	G	A	5: 94,596,394 (GRCm39)	C477Y	probably damaging	Het
Prss1	T	C	6: 41,439,507 (GRCm39)	V80A	probably benign	Het
Psph	G	A	5: 129,847,800 (GRCm39)	R49W	probably benign	Het
Qrich2	T	C	11: 116,347,080 (GRCm39)	Y1248C	possibly damaging	Het
Rlbp1	T	A	7: 79,029,861 (GRCm39)	Y124F	probably damaging	Het
Scn4a	T	A	11: 106,239,995 (GRCm39)	E74V	probably benign	Het
Sdk2	A	T	11: 113,764,039 (GRCm39)	I249N	possibly damaging	Het
Sgsh	A	T	11: 119,237,378 (GRCm39)	L412Q	probably damaging	Het
Shank1	C	A	7: 44,002,452 (GRCm39)	D1390E	probably benign	Het
Snx29	T	A	16: 11,238,649 (GRCm39)		probably null	Het
Spata31d1c	A	G	13: 65,183,937 (GRCm39)	Y493C	probably damaging	Het
Stmn4	G	A	14: 66,593,727 (GRCm39)	G40E	probably damaging	Het
Stox2	A	G	8: 47,656,154 (GRCm39)		probably null	Het
Strada	T	C	11: 106,077,830 (GRCm39)	S45G	unknown	Het
Taco1	G	A	11: 105,962,774 (GRCm39)	G154S	probably benign	Het
Tas2r121	T	C	6: 132,677,505 (GRCm39)	M156V	probably benign	Het
Tbc1d31	A	G	15: 57,804,136 (GRCm39)	S384G	probably benign	Het
Tbc1d9	A	T	8: 83,966,560 (GRCm39)	D387V	probably damaging	Het
Tet3	A	G	6: 83,345,289 (GRCm39)	L1716P	probably damaging	Het
Thbs1	A	G	2: 117,943,843 (GRCm39)	K154E	possibly damaging	Het
Ush2a	T	C	1: 187,999,241 (GRCm39)	Y184H	possibly damaging	Het
Vmn1r235	C	A	17: 21,481,713 (GRCm39)	Q13K	probably benign	Het
Vmn2r15	A	T	5: 109,440,774 (GRCm39)	Y361*	probably null	Het
Vmn2r88	A	T	14: 51,648,315 (GRCm39)		probably null	Het
Vps54	T	C	11: 21,248,831 (GRCm39)	V460A	probably benign	Het
Wdr64	A	G	1: 175,613,147 (GRCm39)	N674S	possibly damaging	Het
Zfp592	A	G	7: 80,673,390 (GRCm39)	D118G	probably benign	Het
Zfp763	A	G	17: 33,237,625 (GRCm39)	Y507H	probably benign	Het
Zfp934	T	C	13: 62,640,705 (GRCm39)	E16G	probably damaging	Het
Zfyve26	G	A	12: 79,337,731 (GRCm39)	L94F	probably damaging	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
R7395:Slc12a6	UTSW	2	112,182,887 (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'- CCCCTGTGAGGTGACGTTTT -3'
(R):5'- TCAAAATAACATAATGTGCATGCATG -3'

Sequencing Primer
(F):5'- CCTTTACTGACCAGCATTAAAAGG -3'
(R):5'- AAATAGGGGGAGGGTGAAAAATC -3'

Posted On

2019-10-17