Incidental Mutation 'R9580:Slc12a5'
ID 722489
Institutional Source Beutler Lab
Gene Symbol Slc12a5
Ensembl Gene ENSMUSG00000017740
Gene Name solute carrier family 12, member 5
Synonyms KCC2
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9580 (G1)
Quality Score 225.009
Status Not validated
Chromosome 2
Chromosomal Location 164802766-164841651 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 164816896 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Phenylalanine to Valine at position 140 (F140V)
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: F117V

PolyPhen 2 Score 0.288 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: F117V

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 probably damaging
Transcript: ENSMUST00000202136
AA Change: F117V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000143973
Gene: ENSMUSG00000017740
AA Change: F117V

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 damaging
Transcript: ENSMUST00000202223
AA Change: F140V

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: F140V

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 damaging
Transcript: ENSMUST00000202479
AA Change: F117V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000144540
Gene: ENSMUSG00000017740
AA Change: F117V

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 damaging
Transcript: ENSMUST00000202623
AA Change: F140V

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: F140V

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.2%
Validation Efficiency
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: 31 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adora2b T C 11: 62,156,145 (GRCm39) M198T probably damaging Het
Agbl2 A G 2: 90,636,248 (GRCm39) T595A probably benign Het
Cep89 A T 7: 35,102,538 (GRCm39) I84F possibly damaging Het
Eda G T X: 99,019,775 (GRCm39) R130L unknown Het
Erp44 T A 4: 48,218,187 (GRCm39) R161* probably null Het
Fcsk A G 8: 111,616,813 (GRCm39) W446R probably damaging Het
Gm12185 T G 11: 48,799,192 (GRCm39) S434R possibly damaging Het
Hmcn2 G T 2: 31,294,875 (GRCm39) A2555S probably benign Het
Idh2 TCCCAGG T 7: 79,748,079 (GRCm39) probably benign Het
Ighv1-61 A G 12: 115,322,993 (GRCm39) S40P possibly damaging Het
Kif26b C T 1: 178,506,643 (GRCm39) Q240* probably null Het
Mapkap1 C T 2: 34,509,878 (GRCm39) T456M probably damaging Het
Ncapg2 A G 12: 116,424,228 (GRCm39) N1137S probably damaging Het
Nectin4 C G 1: 171,211,324 (GRCm39) R283G probably damaging Het
Nos2 A G 11: 78,828,457 (GRCm39) I259V probably benign Het
Or2n1d A T 17: 38,646,320 (GRCm39) T91S possibly damaging Het
Or4c119 T C 2: 88,987,465 (GRCm39) N18S probably benign Het
Pgm2 A T 5: 64,265,092 (GRCm39) N371I possibly damaging Het
Ppargc1a A T 5: 51,620,139 (GRCm39) N733K unknown Het
Ptpn5 A G 7: 46,732,622 (GRCm39) Y345H probably damaging Het
Ptprd C G 4: 75,872,315 (GRCm39) A1134P possibly damaging Het
Rbm47 A C 5: 66,183,877 (GRCm39) M242R possibly damaging Het
Slc22a2 G T 17: 12,803,177 (GRCm39) V4L probably benign Het
Stk26 C T X: 49,930,618 (GRCm39) probably benign Het
Tas2r105 A T 6: 131,663,699 (GRCm39) I243K probably damaging Het
Tmem126b G T 7: 90,118,231 (GRCm39) Y216* probably null Het
Usp25 C T 16: 76,880,682 (GRCm39) T681I probably benign Het
Vmn1r206 C T 13: 22,804,890 (GRCm39) A106T probably damaging Het
Vmn1r39 A T 6: 66,781,915 (GRCm39) N134K probably damaging Het
Vmn1r9 T C 6: 57,048,812 (GRCm39) S296P probably benign Het
Zfp97 T A 17: 17,365,243 (GRCm39) F247L 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
R4039:Slc12a5 UTSW 2 164,834,250 (GRCm39) missense probably benign 0.03
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
R9677:Slc12a5 UTSW 2 164,834,246 (GRCm39) missense possibly damaging 0.66
Predicted Primers PCR Primer
(F):5'- GCATGTGAGAACCTGGGG -3'
(R):5'- AAAGCTCAGGTCGCATGCT -3'

Sequencing Primer
(F):5'- CATGTGAGAACCTGGGGGAAGAG -3'
(R):5'- AGGTCGCATGCTTCCCC -3'
Posted On 2022-08-09