Incidental Mutation 'R6280:Slc12a6'
ID 507873
Institutional Source Beutler Lab
Gene Symbol Slc12a6
Ensembl Gene ENSMUSG00000027130
Gene Name solute carrier family 12, member 6
Synonyms KCC3, gaxp
MMRRC Submission 044450-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.216) question?
Stock # R6280 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 112096659-112193508 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 112167703 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 231 (T231A)
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: T231A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000028549
Gene: ENSMUSG00000027130
AA Change: T231A

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000053666
AA Change: T180A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000051490
Gene: ENSMUSG00000027130
AA Change: T180A

DomainStartEndE-ValueType
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: T216A

PolyPhen 2 Score 0.899 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000106615
Gene: ENSMUSG00000027130
AA Change: T216A

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000110991
AA Change: T231A

PolyPhen 2 Score 0.870 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000106619
Gene: ENSMUSG00000027130
AA Change: T231A

DomainStartEndE-ValueType
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: T216A

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000124314
Gene: ENSMUSG00000096764
AA Change: T216A

DomainStartEndE-ValueType
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
Meta Mutation Damage Score 0.4711 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.5%
  • 20x: 95.9%
Validation Efficiency 100% (75/75)
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: 76 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca12 C T 1: 71,311,619 (GRCm39) D1930N probably benign Het
Adam8 A G 7: 139,564,720 (GRCm39) L667S probably damaging Het
Adcy4 A T 14: 56,016,500 (GRCm39) I317N probably damaging Het
Agpat3 A G 10: 78,120,872 (GRCm39) F102S probably damaging Het
Apbb2 A T 5: 66,522,325 (GRCm39) W443R probably damaging Het
BC049715 T A 6: 136,817,229 (GRCm39) Y156* probably null Het
Bpifc C T 10: 85,813,576 (GRCm39) V323I probably benign Het
Camp T G 9: 109,676,577 (GRCm39) I149L probably benign Het
Cfap20dc T G 14: 8,473,414 (GRCm38) probably null Het
Cibar2 A G 8: 120,898,858 (GRCm39) I94T possibly damaging Het
Cnih1 A G 14: 47,025,634 (GRCm39) probably null Het
Col18a1 A T 10: 76,948,323 (GRCm39) probably benign Het
Dsg4 A T 18: 20,599,724 (GRCm39) D780V probably damaging Het
Dync1i1 G A 6: 5,972,084 (GRCm39) V442I probably benign Het
Fam83g G T 11: 61,594,008 (GRCm39) S514I probably benign Het
Fbxo7 A G 10: 85,864,969 (GRCm39) N93D probably benign Het
Fgf20 G T 8: 40,734,153 (GRCm39) S76* probably null Het
Foxi1 A G 11: 34,157,972 (GRCm39) F18L probably damaging Het
Fxr1 G A 3: 34,100,401 (GRCm39) probably benign Het
Gon4l T A 3: 88,798,195 (GRCm39) L800H probably damaging Het
Gpn3 T A 5: 122,512,022 (GRCm39) S33T probably benign Het
Gria4 T C 9: 4,456,072 (GRCm39) M743V probably damaging Het
Hira A G 16: 18,729,457 (GRCm39) N109D probably damaging Het
Hsd3b3 A G 3: 98,660,621 (GRCm39) probably null Het
Hsf2 T G 10: 57,387,591 (GRCm39) S370A probably benign Het
Htt T A 5: 35,028,103 (GRCm39) D1786E probably benign Het
Ifit1bl2 T A 19: 34,597,534 (GRCm39) R27S possibly damaging Het
Il17rb G A 14: 29,724,928 (GRCm39) A186V probably benign Het
Irak4 G T 15: 94,449,691 (GRCm39) E57* probably null Het
Kcnh2 T A 5: 24,536,921 (GRCm39) H221L probably benign Het
Kdm2b T C 5: 123,016,687 (GRCm39) N1149D probably damaging Het
Kif26a A G 12: 112,141,303 (GRCm39) H702R probably damaging Het
Kmt2e T C 5: 23,704,514 (GRCm39) S1236P possibly damaging Het
Krt77 T A 15: 101,773,910 (GRCm39) D248V probably damaging Het
Lgals3bp T C 11: 118,284,106 (GRCm39) N52S possibly damaging Het
Lhfpl6 T C 3: 53,167,935 (GRCm39) Y170H probably damaging Het
Lpin2 A G 17: 71,539,243 (GRCm39) probably benign Het
Lrig3 T C 10: 125,846,848 (GRCm39) I872T probably benign Het
Lrit3 T C 3: 129,582,412 (GRCm39) E525G probably damaging Het
Lrp1 T C 10: 127,425,453 (GRCm39) T726A probably benign Het
Mep1a A T 17: 43,813,283 (GRCm39) N46K probably damaging Het
Muc16 C A 9: 18,490,613 (GRCm39) probably null Het
N4bp1 A C 8: 87,579,794 (GRCm39) N669K possibly damaging Het
Nelfcd A G 2: 174,257,739 (GRCm39) D26G probably benign Het
Neu4 G A 1: 93,952,873 (GRCm39) S414N probably damaging Het
Nudt9 A G 5: 104,212,935 (GRCm39) D336G probably benign Het
Obscn C A 11: 58,954,509 (GRCm39) G3691V possibly damaging Het
Or4c52 A C 2: 89,845,393 (GRCm39) I40L possibly damaging Het
Or5t17 A G 2: 86,832,364 (GRCm39) N17S probably damaging Het
Pdgfd T A 9: 6,288,627 (GRCm39) S94T probably benign Het
Picalm A G 7: 89,826,770 (GRCm39) H290R probably benign Het
Pou2f3 A T 9: 43,050,634 (GRCm39) L242Q probably damaging Het
Pou2f3 G T 9: 43,050,635 (GRCm39) L242M probably damaging Het
Prkd3 C T 17: 79,289,360 (GRCm39) G187D probably damaging Het
Pwp1 A G 10: 85,710,326 (GRCm39) S49G probably damaging Het
Ralgapa2 A G 2: 146,184,129 (GRCm39) L1626P probably damaging Het
Resf1 T C 6: 149,228,555 (GRCm39) S534P probably damaging Het
Rin2 A G 2: 145,702,939 (GRCm39) Y545C probably damaging Het
Rwdd4a A G 8: 47,995,832 (GRCm39) T71A probably benign Het
Senp7 T C 16: 55,982,738 (GRCm39) F504L possibly damaging Het
Slc13a2 CGTTATCTGT CGT 11: 78,294,306 (GRCm39) probably benign Het
Slc34a1 A G 13: 24,006,377 (GRCm39) S468G probably benign Het
Slc4a10 A G 2: 62,112,310 (GRCm39) N697S probably benign Het
Spint1 T A 2: 119,075,759 (GRCm39) V194E possibly damaging Het
Sptlc2 A T 12: 87,434,905 (GRCm39) M14K probably benign Het
Stard9 A G 2: 120,531,608 (GRCm39) K2622E probably benign Het
Tbc1d5 T C 17: 51,089,338 (GRCm39) N614S probably benign Het
Tdpoz2 A T 3: 93,559,190 (GRCm39) C261S probably benign Het
Tmem150b A T 7: 4,727,373 (GRCm39) I44N probably benign Het
Ttn A G 2: 76,608,502 (GRCm39) L17807P probably damaging Het
Vcan G A 13: 89,873,492 (GRCm39) R121W probably damaging Het
Vmn2r15 T A 5: 109,441,291 (GRCm39) H189L possibly damaging Het
Vmn2r19 A G 6: 123,313,212 (GRCm39) S761G probably benign Het
Wdr11 A T 7: 129,200,830 (GRCm39) K34* probably null Het
Zfp120 A T 2: 149,959,964 (GRCm39) S141R possibly damaging Het
Zfp462 C G 4: 55,010,253 (GRCm39) P740A probably benign Het
Other mutations in Slc12a6
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- GCTAGTCTGTAGGTAGGTTCACC -3'
(R):5'- CCTTAAGCTAAACAGCATTTGTCTCTC -3'

Sequencing Primer
(F):5'- AGGTTCACCCTACCTTGCAATGTTAG -3'
(R):5'- AAACAGCATTTGTCTCTCTGGCTTG -3'
Posted On 2018-03-15