Incidental Mutation 'R5299:Slc12a3'
| ID |
405569 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Slc12a3
|
| Ensembl Gene |
ENSMUSG00000031766 |
| Gene Name |
solute carrier family 12, member 3 |
| Synonyms |
TSC, NCC |
| MMRRC Submission |
042882-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R5299 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
8 |
| Chromosomal Location |
95055829-95092842 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 95078417 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Cysteine
at position 815
(Y815C)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000148455
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034218]
[ENSMUST00000212134]
|
| AlphaFold |
P59158 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000034218
AA Change: Y815C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000034218
Gene: ENSMUSG00000031766
AA Change: Y815C
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:AA_permease_N
|
43 |
114 |
1.5e-30 |
PFAM |
|
Pfam:AA_permease
|
139 |
645 |
3.6e-145 |
PFAM |
|
Pfam:SLC12
|
653 |
801 |
1.4e-53 |
PFAM |
|
Pfam:SLC12
|
787 |
1001 |
2e-85 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000211905
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000211942
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000212041
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000212134
AA Change: Y815C
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000212632
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000212915
|
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.7%
- 20x: 93.5%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit hypomagnesemia, hypocalciurua and abnormal renal distal convoluted tubule morphology, and show significantly reduced arterial blood pressure on a sodium-depleted diet. Mutant kidney cortical collecting ductsdisplay thiazide-sensitive NaCl absorption. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 39 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca13 |
A |
G |
11: 9,381,861 (GRCm39) |
I3838V |
probably damaging |
Het |
| Arid1a |
A |
T |
4: 133,414,537 (GRCm39) |
D1231E |
unknown |
Het |
| Atxn1 |
A |
T |
13: 45,710,730 (GRCm39) |
I734K |
probably benign |
Het |
| Axin1 |
A |
G |
17: 26,392,708 (GRCm39) |
S330G |
probably damaging |
Het |
| Bend3 |
G |
A |
10: 43,369,686 (GRCm39) |
|
probably null |
Het |
| Chodl |
C |
T |
16: 78,738,296 (GRCm39) |
T88I |
probably damaging |
Het |
| Dnah2 |
C |
T |
11: 69,349,746 (GRCm39) |
R2399Q |
probably benign |
Het |
| Dst |
A |
G |
1: 34,174,173 (GRCm39) |
I179M |
probably damaging |
Het |
| Ehmt2 |
C |
T |
17: 35,118,067 (GRCm39) |
R40* |
probably null |
Het |
| Exoc2 |
A |
T |
13: 31,055,901 (GRCm39) |
|
probably null |
Het |
| Grk2 |
T |
C |
19: 4,342,799 (GRCm39) |
E45G |
probably damaging |
Het |
| Ift81 |
T |
C |
5: 122,745,119 (GRCm39) |
Y144C |
probably damaging |
Het |
| Ighv1-15 |
T |
C |
12: 114,620,998 (GRCm39) |
D109G |
probably damaging |
Het |
| Igtp |
T |
C |
11: 58,097,959 (GRCm39) |
W377R |
possibly damaging |
Het |
| Lgr6 |
C |
T |
1: 134,921,748 (GRCm39) |
A199T |
probably damaging |
Het |
| Map2k6 |
A |
G |
11: 110,383,789 (GRCm39) |
D145G |
probably benign |
Het |
| Mcph1 |
T |
C |
8: 18,702,596 (GRCm39) |
|
probably benign |
Het |
| Mdfi |
A |
G |
17: 48,131,759 (GRCm39) |
V95A |
possibly damaging |
Het |
| Mical3 |
A |
G |
6: 120,936,473 (GRCm39) |
L1351P |
possibly damaging |
Het |
| Nbas |
C |
T |
12: 13,491,926 (GRCm39) |
Q1506* |
probably null |
Het |
| Nelfb |
A |
G |
2: 25,100,757 (GRCm39) |
V128A |
probably benign |
Het |
| Otog |
A |
G |
7: 45,938,275 (GRCm39) |
T1995A |
probably benign |
Het |
| Ppp1r7 |
A |
T |
1: 93,280,348 (GRCm39) |
I139L |
probably benign |
Het |
| Ppp2r1b |
A |
G |
9: 50,768,340 (GRCm39) |
D19G |
probably benign |
Het |
| Proca1 |
T |
C |
11: 78,096,078 (GRCm39) |
S150P |
probably damaging |
Het |
| Rhof |
A |
G |
5: 123,258,611 (GRCm39) |
V100A |
probably damaging |
Het |
| Rsbn1 |
G |
C |
3: 103,821,806 (GRCm39) |
G14R |
probably benign |
Het |
| Serinc1 |
A |
G |
10: 57,399,147 (GRCm39) |
I252T |
probably damaging |
Het |
| Skint4 |
A |
T |
4: 111,993,203 (GRCm39) |
I309F |
possibly damaging |
Het |
| Slc25a24 |
A |
G |
3: 109,073,668 (GRCm39) |
S424G |
probably benign |
Het |
| Spint2 |
G |
A |
7: 28,963,151 (GRCm39) |
A49V |
probably damaging |
Het |
| Traf3ip3 |
T |
A |
1: 192,860,483 (GRCm39) |
K480* |
probably null |
Het |
| Ube2g2 |
T |
C |
10: 77,480,379 (GRCm39) |
S162P |
possibly damaging |
Het |
| Ubxn8 |
C |
A |
8: 34,131,947 (GRCm39) |
V7L |
possibly damaging |
Het |
| Vmn1r200 |
T |
A |
13: 22,579,945 (GRCm39) |
C249* |
probably null |
Het |
| Vmn1r38 |
T |
A |
6: 66,753,682 (GRCm39) |
T145S |
probably benign |
Het |
| Wapl |
G |
A |
14: 34,455,765 (GRCm39) |
|
probably null |
Het |
| Wfdc6a |
T |
C |
2: 164,422,311 (GRCm39) |
N96S |
possibly damaging |
Het |
| Zfp503 |
A |
G |
14: 22,035,507 (GRCm39) |
S470P |
probably benign |
Het |
|
| Other mutations in Slc12a3 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01823:Slc12a3
|
APN |
8 |
95,083,724 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01947:Slc12a3
|
APN |
8 |
95,092,447 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
IGL02151:Slc12a3
|
APN |
8 |
95,075,220 (GRCm39) |
missense |
probably benign |
0.26 |
|
IGL02440:Slc12a3
|
APN |
8 |
95,058,310 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03213:Slc12a3
|
APN |
8 |
95,061,933 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
IGL03260:Slc12a3
|
APN |
8 |
95,059,870 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03306:Slc12a3
|
APN |
8 |
95,078,386 (GRCm39) |
missense |
possibly damaging |
0.72 |
|
IGL03329:Slc12a3
|
APN |
8 |
95,092,519 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
avaricious
|
UTSW |
8 |
95,057,100 (GRCm39) |
missense |
probably benign |
0.01 |
|
Pugilist
|
UTSW |
8 |
95,072,401 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R0131:Slc12a3
|
UTSW |
8 |
95,067,511 (GRCm39) |
splice site |
probably benign |
|
|
R0189:Slc12a3
|
UTSW |
8 |
95,082,986 (GRCm39) |
missense |
probably benign |
0.30 |
|
R0330:Slc12a3
|
UTSW |
8 |
95,072,974 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
R0569:Slc12a3
|
UTSW |
8 |
95,057,153 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0715:Slc12a3
|
UTSW |
8 |
95,056,061 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
R1248:Slc12a3
|
UTSW |
8 |
95,059,905 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1565:Slc12a3
|
UTSW |
8 |
95,072,505 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
R2068:Slc12a3
|
UTSW |
8 |
95,072,456 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2108:Slc12a3
|
UTSW |
8 |
95,067,158 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R2273:Slc12a3
|
UTSW |
8 |
95,059,915 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R2274:Slc12a3
|
UTSW |
8 |
95,059,915 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R2275:Slc12a3
|
UTSW |
8 |
95,059,915 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R2433:Slc12a3
|
UTSW |
8 |
95,072,944 (GRCm39) |
missense |
probably benign |
0.00 |
|
R3770:Slc12a3
|
UTSW |
8 |
95,079,668 (GRCm39) |
missense |
probably benign |
|
|
R4429:Slc12a3
|
UTSW |
8 |
95,069,713 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4431:Slc12a3
|
UTSW |
8 |
95,069,713 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4533:Slc12a3
|
UTSW |
8 |
95,083,714 (GRCm39) |
missense |
probably null |
0.02 |
|
R4627:Slc12a3
|
UTSW |
8 |
95,056,012 (GRCm39) |
missense |
probably benign |
|
|
R4856:Slc12a3
|
UTSW |
8 |
95,078,438 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4886:Slc12a3
|
UTSW |
8 |
95,078,438 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4908:Slc12a3
|
UTSW |
8 |
95,075,216 (GRCm39) |
missense |
possibly damaging |
0.76 |
|
R5054:Slc12a3
|
UTSW |
8 |
95,072,979 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5451:Slc12a3
|
UTSW |
8 |
95,083,655 (GRCm39) |
missense |
possibly damaging |
0.61 |
|
R5590:Slc12a3
|
UTSW |
8 |
95,072,416 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5725:Slc12a3
|
UTSW |
8 |
95,057,074 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6038:Slc12a3
|
UTSW |
8 |
95,057,100 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6038:Slc12a3
|
UTSW |
8 |
95,057,100 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6162:Slc12a3
|
UTSW |
8 |
95,072,401 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R6266:Slc12a3
|
UTSW |
8 |
95,085,099 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R6489:Slc12a3
|
UTSW |
8 |
95,061,632 (GRCm39) |
missense |
possibly damaging |
0.96 |
|
R6521:Slc12a3
|
UTSW |
8 |
95,069,741 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R6882:Slc12a3
|
UTSW |
8 |
95,092,546 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
R7051:Slc12a3
|
UTSW |
8 |
95,092,572 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7510:Slc12a3
|
UTSW |
8 |
95,092,477 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7805:Slc12a3
|
UTSW |
8 |
95,071,515 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8152:Slc12a3
|
UTSW |
8 |
95,057,012 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8412:Slc12a3
|
UTSW |
8 |
95,060,695 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8996:Slc12a3
|
UTSW |
8 |
95,056,063 (GRCm39) |
missense |
probably benign |
|
|
R9307:Slc12a3
|
UTSW |
8 |
95,061,625 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9324:Slc12a3
|
UTSW |
8 |
95,083,028 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9515:Slc12a3
|
UTSW |
8 |
95,083,658 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R9564:Slc12a3
|
UTSW |
8 |
95,082,983 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9687:Slc12a3
|
UTSW |
8 |
95,075,208 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
| Predicted Primers |
PCR Primer
(F):5'- ACATTAGCTGTGTCTGGCC -3'
(R):5'- ACAGGCTAAGGCATCTGTCC -3'
Sequencing Primer
(F):5'- GATGCTTCTGGCCACTGCATG -3'
(R):5'- CAGGCTAAGGCATCTGTCCATTTTG -3'
|
| Posted On |
2016-07-22 |
Incidental Mutation