Incidental Mutation 'R4039:Slc12a5'
ID 313828
Institutional Source Beutler Lab
Gene Symbol Slc12a5
Ensembl Gene ENSMUSG00000017740
Gene Name solute carrier family 12, member 5
Synonyms KCC2
MMRRC Submission 041614-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4039 (G1)
Quality Score 225
Status Validated
Chromosome 2
Chromosomal Location 164802766-164841651 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 164834250 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Glycine at position 757 (E757G)
Ref Sequence ENSEMBL: ENSMUSP00000144623 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000099092] [ENSMUST00000202136] [ENSMUST00000202223] [ENSMUST00000202479] [ENSMUST00000202623]
AlphaFold Q91V14
Predicted Effect probably benign
Transcript: ENSMUST00000099092
AA Change: E734G

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: E734G

DomainStartEndE-ValueType
low complexity region 10 22 N/A INTRINSIC
low complexity region 77 90 N/A INTRINSIC
Pfam:AA_permease 102 304 5.2e-22 PFAM
Pfam:AA_permease_2 364 632 1e-17 PFAM
Pfam:AA_permease 389 676 1.9e-42 PFAM
Pfam:SLC12 688 814 2.1e-19 PFAM
Pfam:SLC12 807 959 1.8e-20 PFAM
low complexity region 978 1002 N/A INTRINSIC
Pfam:SLC12 1009 1115 2.1e-15 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000137302
Predicted Effect probably benign
Transcript: ENSMUST00000202136
SMART Domains Protein: ENSMUSP00000143973
Gene: ENSMUSG00000017740

DomainStartEndE-ValueType
low complexity region 10 22 N/A INTRINSIC
low complexity region 77 90 N/A INTRINSIC
Pfam:AA_permease 102 175 2.5e-10 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000202223
AA Change: E757G

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: E757G

DomainStartEndE-ValueType
low complexity region 11 19 N/A INTRINSIC
low complexity region 100 113 N/A INTRINSIC
Pfam:AA_permease 125 327 1e-19 PFAM
Pfam:AA_permease_2 386 655 4.5e-15 PFAM
Pfam:AA_permease 412 699 3.7e-40 PFAM
Pfam:SLC12 711 837 7.2e-17 PFAM
Pfam:SLC12 830 982 6.2e-18 PFAM
low complexity region 1001 1025 N/A INTRINSIC
Pfam:SLC12 1030 1133 8.6e-13 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000202479
SMART Domains Protein: ENSMUSP00000144540
Gene: ENSMUSG00000017740

DomainStartEndE-ValueType
low complexity region 10 22 N/A INTRINSIC
low complexity region 77 90 N/A INTRINSIC
Pfam:AA_permease 102 176 5.2e-10 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000202623
AA Change: E757G

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: E757G

DomainStartEndE-ValueType
low complexity region 11 19 N/A INTRINSIC
low complexity region 100 113 N/A INTRINSIC
Pfam:AA_permease 125 327 5.3e-22 PFAM
Pfam:AA_permease_2 386 655 1.2e-17 PFAM
Pfam:AA_permease 412 699 2e-42 PFAM
Pfam:SLC12 711 837 2.1e-19 PFAM
Pfam:SLC12 830 982 1.8e-20 PFAM
low complexity region 1001 1025 N/A INTRINSIC
Pfam:SLC12 1032 1138 2.2e-15 PFAM
Meta Mutation Damage Score 0.0673 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.5%
  • 10x: 97.0%
  • 20x: 94.0%
Validation Efficiency 98% (48/49)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die within a few minutes of birth of respiratory failure resulting from a motor nerve defect. Mice homozygous for a hypomorphic allele display postnatal lethality and tonic-clonic seizures. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 44 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4933412E24Rik A T 15: 59,888,215 (GRCm39) L75Q possibly damaging Het
Cep290 T C 10: 100,348,263 (GRCm39) probably null Het
Col11a2 A G 17: 34,264,748 (GRCm39) T268A probably benign Het
Crnkl1 T A 2: 145,774,247 (GRCm39) D72V possibly damaging Het
Csn2 C T 5: 87,845,935 (GRCm39) M1I probably null Het
Dhcr24 T C 4: 106,431,075 (GRCm39) F255L probably benign Het
Epn2 A G 11: 61,437,348 (GRCm39) Y75H probably damaging Het
Galnt3 A T 2: 65,915,671 (GRCm39) H563Q probably damaging Het
Galnt9 T C 5: 110,762,074 (GRCm39) V37A probably damaging Het
Glb1l3 A C 9: 26,740,343 (GRCm39) M329R probably damaging Het
Gorab A T 1: 163,224,635 (GRCm39) D55E possibly damaging Het
Herc2 G A 7: 55,806,159 (GRCm39) R2318Q probably damaging Het
Hspa2 T C 12: 76,452,542 (GRCm39) V412A probably damaging Het
Hspb8 A G 5: 116,547,403 (GRCm39) V193A probably benign Het
Ly75 A G 2: 60,183,339 (GRCm39) L481P probably damaging Het
Lyzl1 T C 18: 4,169,140 (GRCm39) L48P probably damaging Het
Mettl27 C T 5: 134,969,463 (GRCm39) Q212* probably null Het
Mmachc T A 4: 116,563,215 (GRCm39) T47S probably damaging Het
Ncam2 C T 16: 81,287,211 (GRCm39) S375L probably benign Het
Ogfrl1 T C 1: 23,418,045 (GRCm39) probably benign Het
Parp9 T C 16: 35,780,417 (GRCm39) L461P probably damaging Het
Pcsk7 A G 9: 45,839,305 (GRCm39) probably null Het
Plekhh1 C A 12: 79,101,957 (GRCm39) H342Q probably benign Het
Prdm13 T G 4: 21,685,774 (GRCm39) probably benign Het
Prkaa2 T C 4: 104,908,444 (GRCm39) N144D probably damaging Het
Ptpn12 A T 5: 21,207,508 (GRCm39) Y283* probably null Het
Rab12 T C 17: 66,807,396 (GRCm39) Y111C possibly damaging Het
Ralgapa1 T C 12: 55,842,486 (GRCm39) N61S probably damaging Het
Rims1 T C 1: 22,514,793 (GRCm39) S537G probably damaging Het
Sash1 G T 10: 8,605,391 (GRCm39) P1000T probably damaging Het
Skint5 G T 4: 113,743,011 (GRCm39) T352K unknown Het
Sycp2 C A 2: 178,022,720 (GRCm39) M470I possibly damaging Het
Szt2 T C 4: 118,222,149 (GRCm39) probably benign Het
Tbc1d1 A G 5: 64,473,771 (GRCm39) T765A probably damaging Het
Tgfbr2 T C 9: 116,004,105 (GRCm39) M1V probably null Het
Tnfrsf11a A G 1: 105,755,464 (GRCm39) probably null Het
Trim43b A G 9: 88,973,400 (GRCm39) L111P probably damaging Het
Ttbk2 A T 2: 120,576,276 (GRCm39) S900R probably benign Het
Unc79 G A 12: 103,041,208 (GRCm39) C747Y possibly damaging Het
Vmn1r218 T C 13: 23,320,971 (GRCm39) V26A possibly damaging Het
Vmn2r115 A T 17: 23,564,077 (GRCm39) Y83F probably benign Het
Zfp536 A T 7: 37,268,975 (GRCm39) L147Q probably damaging Het
Zfp931 T A 2: 177,709,777 (GRCm39) Q203L possibly damaging Het
Zswim2 G A 2: 83,746,338 (GRCm39) H367Y probably damaging Het
Other mutations in Slc12a5
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00324:Slc12a5 APN 2 164,839,041 (GRCm39) missense probably damaging 1.00
IGL00425:Slc12a5 APN 2 164,825,201 (GRCm39) missense probably damaging 1.00
IGL00976:Slc12a5 APN 2 164,821,224 (GRCm39) missense probably damaging 1.00
IGL01654:Slc12a5 APN 2 164,815,675 (GRCm39) missense possibly damaging 0.91
IGL01905:Slc12a5 APN 2 164,832,301 (GRCm39) missense probably benign 0.02
IGL02205:Slc12a5 APN 2 164,838,399 (GRCm39) missense probably benign 0.03
IGL02510:Slc12a5 APN 2 164,824,728 (GRCm39) splice site probably benign
IGL02746:Slc12a5 APN 2 164,816,836 (GRCm39) missense probably benign 0.01
G1Funyon:Slc12a5 UTSW 2 164,835,611 (GRCm39) missense probably damaging 0.98
R0051:Slc12a5 UTSW 2 164,828,583 (GRCm39) missense probably damaging 1.00
R0254:Slc12a5 UTSW 2 164,839,165 (GRCm39) critical splice donor site probably null
R0412:Slc12a5 UTSW 2 164,835,982 (GRCm39) missense probably benign 0.05
R0587:Slc12a5 UTSW 2 164,818,453 (GRCm39) missense probably damaging 1.00
R0835:Slc12a5 UTSW 2 164,835,958 (GRCm39) missense probably damaging 0.97
R0932:Slc12a5 UTSW 2 164,838,805 (GRCm39) splice site probably benign
R1643:Slc12a5 UTSW 2 164,835,947 (GRCm39) missense probably benign 0.01
R1700:Slc12a5 UTSW 2 164,834,296 (GRCm39) missense possibly damaging 0.94
R1760:Slc12a5 UTSW 2 164,838,048 (GRCm39) missense probably damaging 0.99
R2063:Slc12a5 UTSW 2 164,839,067 (GRCm39) missense probably damaging 1.00
R2293:Slc12a5 UTSW 2 164,834,250 (GRCm39) missense probably benign 0.03
R2412:Slc12a5 UTSW 2 164,818,382 (GRCm39) critical splice donor site probably null
R3035:Slc12a5 UTSW 2 164,822,178 (GRCm39) missense probably benign 0.06
R3116:Slc12a5 UTSW 2 164,838,101 (GRCm39) splice site probably null
R3412:Slc12a5 UTSW 2 164,810,351 (GRCm39) missense probably benign 0.26
R3788:Slc12a5 UTSW 2 164,835,695 (GRCm39) missense probably damaging 1.00
R4174:Slc12a5 UTSW 2 164,821,410 (GRCm39) missense probably damaging 1.00
R4492:Slc12a5 UTSW 2 164,821,263 (GRCm39) missense probably benign 0.08
R4608:Slc12a5 UTSW 2 164,815,685 (GRCm39) missense probably damaging 0.99
R4750:Slc12a5 UTSW 2 164,824,851 (GRCm39) missense probably benign 0.06
R4994:Slc12a5 UTSW 2 164,825,285 (GRCm39) splice site probably null
R5103:Slc12a5 UTSW 2 164,834,353 (GRCm39) missense probably damaging 1.00
R5539:Slc12a5 UTSW 2 164,829,126 (GRCm39) missense possibly damaging 0.94
R5632:Slc12a5 UTSW 2 164,829,141 (GRCm39) missense possibly damaging 0.86
R5771:Slc12a5 UTSW 2 164,815,688 (GRCm39) missense possibly damaging 0.88
R6139:Slc12a5 UTSW 2 164,834,231 (GRCm39) missense probably damaging 0.98
R6336:Slc12a5 UTSW 2 164,834,384 (GRCm39) splice site probably null
R6581:Slc12a5 UTSW 2 164,829,035 (GRCm39) missense probably damaging 1.00
R6706:Slc12a5 UTSW 2 164,830,509 (GRCm39) missense probably damaging 1.00
R6886:Slc12a5 UTSW 2 164,824,825 (GRCm39) missense probably benign
R7134:Slc12a5 UTSW 2 164,816,878 (GRCm39) missense probably damaging 1.00
R7310:Slc12a5 UTSW 2 164,834,360 (GRCm39) missense probably damaging 1.00
R7402:Slc12a5 UTSW 2 164,824,852 (GRCm39) missense probably benign 0.01
R8079:Slc12a5 UTSW 2 164,834,372 (GRCm39) missense probably damaging 1.00
R8301:Slc12a5 UTSW 2 164,835,611 (GRCm39) missense probably damaging 0.98
R9105:Slc12a5 UTSW 2 164,838,114 (GRCm39) missense probably benign
R9132:Slc12a5 UTSW 2 164,835,876 (GRCm39) intron probably benign
R9431:Slc12a5 UTSW 2 164,832,178 (GRCm39) missense possibly damaging 0.95
R9580:Slc12a5 UTSW 2 164,816,896 (GRCm39) missense probably damaging 0.99
R9677:Slc12a5 UTSW 2 164,834,246 (GRCm39) missense possibly damaging 0.66
Predicted Primers PCR Primer
(F):5'- GGCTTATCTGTGAGGAGCAG -3'
(R):5'- TGAAGTTCCTCCATGTCTGATG -3'

Sequencing Primer
(F):5'- GGGTCCTAGAGTTGGATAAGATC -3'
(R):5'- AAGTTCCTCCATGTCTGATGATCCTC -3'
Posted On 2015-04-30