Incidental Mutation 'R5766:Slc8a1'
| ID |
446308 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Slc8a1
|
| Ensembl Gene |
ENSMUSG00000054640 |
| Gene Name |
solute carrier family 8 (sodium/calcium exchanger), member 1 |
| Synonyms |
Ncx1, D930008O12Rik |
| MMRRC Submission |
044424-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5766 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
17 |
| Chromosomal Location |
81680534-82045806 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 81956390 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Cysteine
at position 216
(Y216C)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000126373
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000086538]
[ENSMUST00000163123]
[ENSMUST00000163680]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000086538
AA Change: Y216C
PolyPhen 2
Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000083725
Gene: ENSMUSG00000054640
AA Change: Y216C
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
32 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
77 |
248 |
3.8e-38 |
PFAM |
|
Pfam:Na_Ca_ex_C
|
251 |
386 |
2e-53 |
PFAM |
|
Calx_beta
|
393 |
493 |
1.28e-49 |
SMART |
|
Calx_beta
|
524 |
624 |
8.25e-44 |
SMART |
|
low complexity region
|
754 |
765 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
796 |
961 |
2.4e-29 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000163123
AA Change: Y216C
PolyPhen 2
Score 0.808 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000132809
Gene: ENSMUSG00000054640
AA Change: Y216C
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
32 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
87 |
246 |
4.6e-38 |
PFAM |
|
coiled coil region
|
313 |
332 |
N/A |
INTRINSIC |
|
Calx_beta
|
393 |
493 |
1.28e-49 |
SMART |
|
Calx_beta
|
524 |
624 |
8.25e-44 |
SMART |
|
low complexity region
|
742 |
753 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
794 |
947 |
1.2e-28 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000163680
AA Change: Y216C
PolyPhen 2
Score 0.966 (Sensitivity: 0.77; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000126373
Gene: ENSMUSG00000054640
AA Change: Y216C
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
32 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
77 |
248 |
3.8e-38 |
PFAM |
|
Pfam:Na_Ca_ex_C
|
251 |
386 |
2e-53 |
PFAM |
|
Calx_beta
|
393 |
493 |
1.28e-49 |
SMART |
|
Calx_beta
|
524 |
624 |
8.25e-44 |
SMART |
|
low complexity region
|
754 |
765 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
796 |
961 |
2.4e-29 |
PFAM |
|
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.7%
- 10x: 97.3%
- 20x: 95.5%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] In cardiac myocytes, Ca(2+) concentrations alternate between high levels during contraction and low levels during relaxation. The increase in Ca(2+) concentration during contraction is primarily due to release of Ca(2+) from intracellular stores. However, some Ca(2+) also enters the cell through the sarcolemma (plasma membrane). During relaxation, Ca(2+) is sequestered within the intracellular stores. To prevent overloading of intracellular stores, the Ca(2+) that entered across the sarcolemma must be extruded from the cell. The Na(+)-Ca(2+) exchanger is the primary mechanism by which the Ca(2+) is extruded from the cell during relaxation. In the heart, the exchanger may play a key role in digitalis action. The exchanger is the dominant mechanism in returning the cardiac myocyte to its resting state following excitation.[supplied by OMIM, Apr 2004]
PHENOTYPE: Homozygotes for targeted null mutations have underdeveloped, nonbeating hearts with massive apoptosis of myocytes, a dilated pericardium and die around embryonic day 9.5. Heterozygotes exhibit altered responses to experimental cardiac pressure overload. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 52 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aadacl3 |
A |
G |
4: 144,182,439 (GRCm39) |
V343A |
probably damaging |
Het |
| AI429214 |
TCCCTGATGAAC |
TC |
8: 37,461,383 (GRCm39) |
|
probably null |
Het |
| Arid2 |
A |
G |
15: 96,270,086 (GRCm39) |
T1400A |
probably benign |
Het |
| Arrdc1 |
G |
A |
2: 24,816,417 (GRCm39) |
T184I |
probably damaging |
Het |
| Aspm |
T |
C |
1: 139,406,740 (GRCm39) |
F1876L |
probably damaging |
Het |
| Calhm1 |
C |
T |
19: 47,132,142 (GRCm39) |
V158I |
probably benign |
Het |
| Caly |
T |
C |
7: 139,650,310 (GRCm39) |
K211E |
probably benign |
Het |
| Cenpe |
T |
C |
3: 134,954,174 (GRCm39) |
L1677P |
probably damaging |
Het |
| Cttnbp2 |
A |
G |
6: 18,381,032 (GRCm39) |
V1388A |
possibly damaging |
Het |
| Dgkd |
C |
T |
1: 87,808,171 (GRCm39) |
R80* |
probably null |
Het |
| Dnah3 |
A |
T |
7: 119,577,445 (GRCm39) |
I2072N |
probably damaging |
Het |
| Dnah8 |
A |
G |
17: 30,909,235 (GRCm39) |
I1020M |
probably benign |
Het |
| Drc3 |
T |
C |
11: 60,284,647 (GRCm39) |
V484A |
probably benign |
Het |
| Efcab8 |
A |
G |
2: 153,622,912 (GRCm39) |
D27G |
possibly damaging |
Het |
| Fat4 |
G |
A |
3: 38,943,617 (GRCm39) |
G837R |
probably damaging |
Het |
| Fcgbpl1 |
G |
A |
7: 27,836,754 (GRCm39) |
W224* |
probably null |
Het |
| Fgb |
A |
T |
3: 82,953,483 (GRCm39) |
C96S |
probably damaging |
Het |
| Flt4 |
G |
C |
11: 49,517,513 (GRCm39) |
W278C |
possibly damaging |
Het |
| Fmnl2 |
T |
C |
2: 52,991,466 (GRCm39) |
V327A |
probably damaging |
Het |
| Fras1 |
A |
T |
5: 96,879,548 (GRCm39) |
Y2455F |
possibly damaging |
Het |
| Gm10549 |
C |
A |
18: 33,597,358 (GRCm39) |
|
probably benign |
Het |
| Gm13872 |
T |
A |
2: 102,568,254 (GRCm39) |
I88N |
probably damaging |
Het |
| Hoxa6 |
A |
G |
6: 52,185,394 (GRCm39) |
S71P |
probably benign |
Het |
| Hunk |
T |
A |
16: 90,250,627 (GRCm39) |
C148S |
probably damaging |
Het |
| Ighv1-18 |
A |
C |
12: 114,646,527 (GRCm39) |
S26A |
probably damaging |
Het |
| Impg2 |
T |
G |
16: 56,080,183 (GRCm39) |
D553E |
possibly damaging |
Het |
| Ints1 |
A |
G |
5: 139,757,900 (GRCm39) |
I266T |
probably benign |
Het |
| Kpna3 |
G |
T |
14: 61,640,463 (GRCm39) |
T33K |
probably benign |
Het |
| Lamb1 |
A |
G |
12: 31,349,930 (GRCm39) |
D622G |
probably damaging |
Het |
| Lamp3 |
T |
C |
16: 19,520,067 (GRCm39) |
T39A |
probably damaging |
Het |
| Mnt |
C |
T |
11: 74,733,904 (GRCm39) |
|
probably benign |
Het |
| Msh4 |
A |
G |
3: 153,573,477 (GRCm39) |
S726P |
probably damaging |
Het |
| Or13a25 |
T |
A |
7: 140,247,266 (GRCm39) |
V22E |
probably benign |
Het |
| Pah |
A |
C |
10: 87,403,209 (GRCm39) |
K195Q |
probably damaging |
Het |
| Pdc |
T |
A |
1: 150,209,251 (GRCm39) |
*245K |
probably null |
Het |
| Pdzd8 |
A |
T |
19: 59,288,972 (GRCm39) |
H809Q |
possibly damaging |
Het |
| Plekhd1 |
A |
T |
12: 80,769,140 (GRCm39) |
I467L |
probably benign |
Het |
| Ppp2ca |
A |
G |
11: 52,004,014 (GRCm39) |
D57G |
probably damaging |
Het |
| Ralgapa1 |
A |
T |
12: 55,867,551 (GRCm39) |
M1K |
probably null |
Het |
| Rfx2 |
T |
A |
17: 57,110,587 (GRCm39) |
D133V |
probably benign |
Het |
| Scfd2 |
A |
T |
5: 74,623,312 (GRCm39) |
L407Q |
probably damaging |
Het |
| Scp2d1 |
T |
A |
2: 144,665,957 (GRCm39) |
S99T |
possibly damaging |
Het |
| Sec63 |
A |
T |
10: 42,677,677 (GRCm39) |
N261I |
probably damaging |
Het |
| Son |
T |
A |
16: 91,461,875 (GRCm39) |
|
probably benign |
Het |
| Syce1 |
T |
C |
7: 140,357,894 (GRCm39) |
E285G |
probably damaging |
Het |
| Taar7a |
G |
T |
10: 23,869,260 (GRCm39) |
S40R |
probably benign |
Het |
| Ube3a |
A |
T |
7: 58,925,807 (GRCm39) |
D216V |
possibly damaging |
Het |
| Vgll2 |
A |
G |
10: 51,903,659 (GRCm39) |
D174G |
probably damaging |
Het |
| Vmn2r17 |
A |
T |
5: 109,575,139 (GRCm39) |
T149S |
possibly damaging |
Het |
| Zbtb39 |
G |
T |
10: 127,578,557 (GRCm39) |
C377F |
probably damaging |
Het |
| Zfp820 |
T |
A |
17: 22,038,983 (GRCm39) |
N115I |
probably damaging |
Het |
| Zfp948 |
T |
C |
17: 21,805,078 (GRCm39) |
S23P |
probably benign |
Het |
|
| Other mutations in Slc8a1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00549:Slc8a1
|
APN |
17 |
81,956,600 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00572:Slc8a1
|
APN |
17 |
81,696,155 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00777:Slc8a1
|
APN |
17 |
81,956,009 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00857:Slc8a1
|
APN |
17 |
81,955,308 (GRCm39) |
missense |
probably benign |
0.03 |
|
IGL01068:Slc8a1
|
APN |
17 |
81,696,371 (GRCm39) |
missense |
probably benign |
0.09 |
|
IGL01089:Slc8a1
|
APN |
17 |
81,696,310 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01089:Slc8a1
|
APN |
17 |
81,955,710 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01510:Slc8a1
|
APN |
17 |
81,955,794 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01677:Slc8a1
|
APN |
17 |
81,956,036 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01862:Slc8a1
|
APN |
17 |
81,749,630 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02003:Slc8a1
|
APN |
17 |
81,735,625 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
IGL02500:Slc8a1
|
APN |
17 |
81,696,142 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02556:Slc8a1
|
APN |
17 |
81,956,173 (GRCm39) |
missense |
probably benign |
0.24 |
|
IGL02800:Slc8a1
|
APN |
17 |
81,715,752 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL03308:Slc8a1
|
APN |
17 |
81,749,624 (GRCm39) |
unclassified |
probably benign |
|
|
IGL03391:Slc8a1
|
APN |
17 |
81,740,067 (GRCm39) |
splice site |
probably benign |
|
|
cardinal
|
UTSW |
17 |
81,955,836 (GRCm39) |
missense |
probably damaging |
0.99 |
|
encyclical
|
UTSW |
17 |
81,956,883 (GRCm39) |
missense |
probably damaging |
1.00 |
|
PIT4498001:Slc8a1
|
UTSW |
17 |
81,956,269 (GRCm39) |
nonsense |
probably null |
|
|
R0067:Slc8a1
|
UTSW |
17 |
81,745,188 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0067:Slc8a1
|
UTSW |
17 |
81,745,188 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0485:Slc8a1
|
UTSW |
17 |
81,955,422 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0667:Slc8a1
|
UTSW |
17 |
81,956,310 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0845:Slc8a1
|
UTSW |
17 |
81,745,177 (GRCm39) |
missense |
probably benign |
0.05 |
|
R1073:Slc8a1
|
UTSW |
17 |
81,955,836 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1417:Slc8a1
|
UTSW |
17 |
81,715,709 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1510:Slc8a1
|
UTSW |
17 |
81,955,547 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1546:Slc8a1
|
UTSW |
17 |
81,955,676 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1625:Slc8a1
|
UTSW |
17 |
81,956,670 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1806:Slc8a1
|
UTSW |
17 |
81,955,916 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1879:Slc8a1
|
UTSW |
17 |
81,955,442 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2025:Slc8a1
|
UTSW |
17 |
81,956,541 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2187:Slc8a1
|
UTSW |
17 |
81,955,982 (GRCm39) |
missense |
possibly damaging |
0.48 |
|
R2198:Slc8a1
|
UTSW |
17 |
81,715,685 (GRCm39) |
nonsense |
probably null |
|
|
R3856:Slc8a1
|
UTSW |
17 |
81,955,803 (GRCm39) |
missense |
probably benign |
|
|
R4067:Slc8a1
|
UTSW |
17 |
81,955,703 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4224:Slc8a1
|
UTSW |
17 |
81,956,781 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4225:Slc8a1
|
UTSW |
17 |
81,956,781 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5028:Slc8a1
|
UTSW |
17 |
81,956,702 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R5307:Slc8a1
|
UTSW |
17 |
81,956,653 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5787:Slc8a1
|
UTSW |
17 |
81,696,166 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5902:Slc8a1
|
UTSW |
17 |
81,715,511 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5913:Slc8a1
|
UTSW |
17 |
81,955,431 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6017:Slc8a1
|
UTSW |
17 |
81,955,683 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6481:Slc8a1
|
UTSW |
17 |
81,696,347 (GRCm39) |
missense |
probably benign |
|
|
R6670:Slc8a1
|
UTSW |
17 |
81,956,883 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6714:Slc8a1
|
UTSW |
17 |
81,715,678 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6914:Slc8a1
|
UTSW |
17 |
81,715,549 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6919:Slc8a1
|
UTSW |
17 |
81,696,301 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6942:Slc8a1
|
UTSW |
17 |
81,715,549 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7057:Slc8a1
|
UTSW |
17 |
81,956,524 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7431:Slc8a1
|
UTSW |
17 |
81,749,092 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7447:Slc8a1
|
UTSW |
17 |
81,956,435 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7480:Slc8a1
|
UTSW |
17 |
81,956,649 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7572:Slc8a1
|
UTSW |
17 |
81,749,200 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8056:Slc8a1
|
UTSW |
17 |
81,955,352 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8326:Slc8a1
|
UTSW |
17 |
81,715,535 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8782:Slc8a1
|
UTSW |
17 |
81,955,442 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8905:Slc8a1
|
UTSW |
17 |
81,749,084 (GRCm39) |
missense |
probably benign |
0.05 |
|
R8987:Slc8a1
|
UTSW |
17 |
81,955,282 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R9057:Slc8a1
|
UTSW |
17 |
81,955,479 (GRCm39) |
missense |
probably benign |
|
|
R9441:Slc8a1
|
UTSW |
17 |
81,956,498 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9616:Slc8a1
|
UTSW |
17 |
81,955,407 (GRCm39) |
missense |
probably benign |
0.25 |
|
R9657:Slc8a1
|
UTSW |
17 |
81,955,244 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0024:Slc8a1
|
UTSW |
17 |
81,740,191 (GRCm39) |
missense |
probably benign |
0.11 |
|
Z1186:Slc8a1
|
UTSW |
17 |
81,955,311 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TTGGAAGCTGGTCTGTCTCC -3'
(R):5'- AGTCATTGAAGTGTGCGGC -3'
Sequencing Primer
(F):5'- GAAGCTGGTCTGTCTCCTTCATG -3'
(R):5'- AAGTGTGCGGCCATAACTTC -3'
|
| Posted On |
2016-11-21 |
Incidental Mutation