Incidental Mutation 'R0587:Slc12a5'
| ID |
55796 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Slc12a5
|
| Ensembl Gene |
ENSMUSG00000017740 |
| Gene Name |
solute carrier family 12, member 5 |
| Synonyms |
KCC2 |
| MMRRC Submission |
038777-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0587 (G1)
|
| Quality Score |
220 |
|
Status
|
Validated
|
| Chromosome |
2 |
| Chromosomal Location |
164802766-164841651 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 164818453 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Isoleucine
at position 217
(M217I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000144623
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000099092]
[ENSMUST00000202136]
[ENSMUST00000202223]
[ENSMUST00000202479]
[ENSMUST00000202623]
|
| AlphaFold |
Q91V14 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000099092
AA Change: M194I
PolyPhen 2
Score 0.568 (Sensitivity: 0.88; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: M194I
| Domain | Start | End | E-Value | Type |
|---|
|
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: ENSMUST00000124372
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000202136
|
| SMART Domains |
Protein: ENSMUSP00000143973
Gene: ENSMUSG00000017740
| Domain | Start | End | E-Value | Type |
|---|
|
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: M217I
PolyPhen 2
Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: M217I
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
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: M217I
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: M217I
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000208579
|
| Meta Mutation Damage Score |
0.7677 |
| Coding Region Coverage |
- 1x: 99.4%
- 3x: 98.9%
- 10x: 97.6%
- 20x: 95.3%
|
| Validation Efficiency |
94% (34/36) |
| 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: 33 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2310061I04Rik |
T |
C |
17: 36,203,855 (GRCm39) |
*212W |
probably null |
Het |
| Abca1 |
A |
G |
4: 53,107,035 (GRCm39) |
Y231H |
probably benign |
Het |
| Abca5 |
T |
G |
11: 110,202,203 (GRCm39) |
I401L |
probably benign |
Het |
| Ak2 |
A |
G |
4: 128,896,171 (GRCm39) |
D112G |
probably damaging |
Het |
| Ankrd60 |
T |
A |
2: 173,410,644 (GRCm39) |
D292V |
possibly damaging |
Het |
| Bank1 |
A |
G |
3: 135,919,798 (GRCm39) |
|
probably benign |
Het |
| Bod1l |
G |
A |
5: 41,978,980 (GRCm39) |
S778L |
probably benign |
Het |
| Cep76 |
C |
A |
18: 67,756,245 (GRCm39) |
E529* |
probably null |
Het |
| Col24a1 |
T |
C |
3: 144,998,906 (GRCm39) |
V13A |
possibly damaging |
Het |
| Ctsc |
T |
A |
7: 87,946,437 (GRCm39) |
H154Q |
probably benign |
Het |
| Ctsf |
A |
G |
19: 4,905,766 (GRCm39) |
E87G |
probably benign |
Het |
| Dmxl1 |
A |
T |
18: 50,068,374 (GRCm39) |
T2716S |
probably benign |
Het |
| Espl1 |
A |
G |
15: 102,212,382 (GRCm39) |
|
probably benign |
Het |
| Fcsk |
T |
A |
8: 111,609,957 (GRCm39) |
Q1019L |
probably damaging |
Het |
| Hnrnpul1 |
T |
A |
7: 25,444,657 (GRCm39) |
Y217F |
possibly damaging |
Het |
| Kmt2a |
A |
T |
9: 44,758,831 (GRCm39) |
M1039K |
probably damaging |
Het |
| Large1 |
T |
C |
8: 73,585,961 (GRCm39) |
N382D |
probably damaging |
Het |
| Madd |
A |
G |
2: 90,977,230 (GRCm39) |
V1402A |
probably damaging |
Het |
| Mlh3 |
C |
T |
12: 85,313,193 (GRCm39) |
V998M |
probably benign |
Het |
| Myo1c |
A |
G |
11: 75,548,616 (GRCm39) |
Y71C |
probably damaging |
Het |
| Myt1l |
G |
A |
12: 29,861,634 (GRCm39) |
D139N |
unknown |
Het |
| Nes |
C |
A |
3: 87,885,876 (GRCm39) |
H1378Q |
probably benign |
Het |
| Or4c12 |
T |
C |
2: 89,773,736 (GRCm39) |
H241R |
probably damaging |
Het |
| Otud6b |
T |
C |
4: 14,815,661 (GRCm39) |
E243G |
probably benign |
Het |
| Pak3 |
TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC |
TTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC |
X: 142,526,889 (GRCm39) |
|
probably benign |
Het |
| Pcm1 |
G |
T |
8: 41,739,088 (GRCm39) |
R912L |
probably damaging |
Het |
| Piezo2 |
A |
G |
18: 63,155,497 (GRCm39) |
I2449T |
possibly damaging |
Het |
| Sorl1 |
C |
A |
9: 41,895,802 (GRCm39) |
W1784C |
probably damaging |
Het |
| Spatc1l |
A |
G |
10: 76,400,011 (GRCm39) |
R178G |
possibly damaging |
Het |
| Strada |
A |
C |
11: 106,061,790 (GRCm39) |
Y154D |
probably damaging |
Het |
| Syt6 |
A |
G |
3: 103,532,887 (GRCm39) |
T424A |
probably damaging |
Het |
| Tbx1 |
C |
T |
16: 18,402,243 (GRCm39) |
A245T |
possibly damaging |
Het |
| Tmem143 |
T |
C |
7: 45,556,478 (GRCm39) |
L161P |
probably damaging |
Het |
|
| Other mutations in Slc12a5 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
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'- GCAAACTCCATGCAGAGTGGTTGG -3'
(R):5'- ATGACATGGGCTGTCACTGTTCC -3'
Sequencing Primer
(F):5'- GAGGTCTAGAGAAACCTTCTTCTGTC -3'
(R):5'- cgtatctcgtctccccaacc -3'
|
| Posted On |
2013-07-11 |
Incidental Mutation