Incidental Mutation 'R0062:Slc8b1'
| ID |
17111 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Slc8b1
|
| Ensembl Gene |
ENSMUSG00000032754 |
| Gene Name |
solute carrier family 8 (sodium/lithium/calcium exchanger), member B1 |
| Synonyms |
NCLX, NCKX6, Slc24a6 |
| MMRRC Submission |
038354-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R0062 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
120649233-120672089 bp(+) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
T to A
at 120659928 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000107521
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000068326]
[ENSMUST00000076051]
[ENSMUST00000111889]
[ENSMUST00000111890]
[ENSMUST00000140329]
|
| AlphaFold |
Q925Q3 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000068326
|
| SMART Domains |
Protein: ENSMUSP00000064714
Gene: ENSMUSG00000032754
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
103 |
246 |
5.7e-25 |
PFAM |
|
low complexity region
|
262 |
275 |
N/A |
INTRINSIC |
|
low complexity region
|
337 |
351 |
N/A |
INTRINSIC |
|
transmembrane domain
|
360 |
382 |
N/A |
INTRINSIC |
|
transmembrane domain
|
387 |
409 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
421 |
574 |
1.8e-29 |
PFAM |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000076051
|
| SMART Domains |
Protein: ENSMUSP00000075428
Gene: ENSMUSG00000032754
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
113 |
244 |
9.2e-19 |
PFAM |
|
low complexity region
|
262 |
275 |
N/A |
INTRINSIC |
|
transmembrane domain
|
323 |
345 |
N/A |
INTRINSIC |
|
transmembrane domain
|
360 |
382 |
N/A |
INTRINSIC |
|
transmembrane domain
|
387 |
409 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
431 |
477 |
2.3e-8 |
PFAM |
|
low complexity region
|
507 |
519 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000111889
|
| SMART Domains |
Protein: ENSMUSP00000107520
Gene: ENSMUSG00000032754
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
113 |
232 |
2.5e-16 |
PFAM |
|
low complexity region
|
281 |
295 |
N/A |
INTRINSIC |
|
transmembrane domain
|
304 |
326 |
N/A |
INTRINSIC |
|
transmembrane domain
|
331 |
353 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
375 |
516 |
1.7e-27 |
PFAM |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000111890
|
| SMART Domains |
Protein: ENSMUSP00000107521
Gene: ENSMUSG00000032754
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
116 |
227 |
2.8e-12 |
PFAM |
|
low complexity region
|
245 |
258 |
N/A |
INTRINSIC |
|
low complexity region
|
320 |
334 |
N/A |
INTRINSIC |
|
transmembrane domain
|
343 |
365 |
N/A |
INTRINSIC |
|
transmembrane domain
|
370 |
392 |
N/A |
INTRINSIC |
|
Pfam:Na_Ca_ex
|
414 |
555 |
3.2e-27 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000123326
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000140329
|
| SMART Domains |
Protein: ENSMUSP00000117260
Gene: ENSMUSG00000032754
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.9488 |
| Coding Region Coverage |
- 1x: 90.3%
- 3x: 88.1%
- 10x: 83.4%
- 20x: 77.5%
|
| Validation Efficiency |
91% (72/79) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] SLC24A6 belongs to a family of potassium-dependent sodium/calcium exchangers that maintain cellular calcium homeostasis through the electrogenic countertransport of 4 sodium ions for 1 calcium ion and 1 potassium ion (Cai and Lytton, 2004 [PubMed 14625281]).[supplied by OMIM, Mar 2008]
|
| Allele List at MGI |
All alleles(22) : Targeted(3) Gene trapped(19)
|
| Other mutations in this stock |
Total: 55 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4921513I03Rik |
G |
T |
10: 120,614,511 (GRCm39) |
|
probably benign |
Het |
| Abi2 |
T |
A |
1: 60,492,884 (GRCm39) |
N182K |
probably benign |
Het |
| Adam25 |
A |
T |
8: 41,207,829 (GRCm39) |
H365L |
probably damaging |
Het |
| Ankfy1 |
T |
A |
11: 72,603,030 (GRCm39) |
Y20N |
probably damaging |
Het |
| Arhgef28 |
A |
T |
13: 98,093,150 (GRCm39) |
I977N |
possibly damaging |
Het |
| Cacna1b |
A |
G |
2: 24,648,343 (GRCm39) |
Y161H |
probably damaging |
Het |
| Cacna1c |
T |
C |
6: 118,579,198 (GRCm39) |
D1480G |
probably damaging |
Het |
| Chl1 |
A |
T |
6: 103,726,613 (GRCm39) |
Y1143F |
unknown |
Het |
| Clk3 |
A |
G |
9: 57,659,449 (GRCm39) |
M533T |
probably damaging |
Het |
| Clstn1 |
G |
A |
4: 149,719,253 (GRCm39) |
V361M |
probably damaging |
Het |
| Cnbd1 |
A |
G |
4: 18,860,504 (GRCm39) |
I414T |
possibly damaging |
Het |
| Commd3 |
A |
T |
2: 18,679,514 (GRCm39) |
|
probably null |
Het |
| Dnah8 |
T |
A |
17: 30,984,685 (GRCm39) |
F3128I |
probably damaging |
Het |
| Dock1 |
A |
G |
7: 134,379,224 (GRCm39) |
|
probably null |
Het |
| Dpysl3 |
C |
T |
18: 43,466,941 (GRCm39) |
|
probably null |
Het |
| Ebf2 |
T |
A |
14: 67,475,989 (GRCm39) |
|
probably benign |
Het |
| F830045P16Rik |
T |
C |
2: 129,305,624 (GRCm39) |
E250G |
possibly damaging |
Het |
| Fmn2 |
A |
T |
1: 174,436,015 (GRCm39) |
|
probably benign |
Het |
| Fryl |
T |
C |
5: 73,179,621 (GRCm39) |
I2929V |
probably benign |
Het |
| Gm11232 |
T |
A |
4: 71,675,112 (GRCm39) |
Q130L |
possibly damaging |
Het |
| Gna15 |
A |
G |
10: 81,348,239 (GRCm39) |
|
probably null |
Het |
| Gtf3c5 |
T |
C |
2: 28,462,198 (GRCm39) |
|
probably benign |
Het |
| Irs2 |
G |
A |
8: 11,055,723 (GRCm39) |
T903I |
possibly damaging |
Het |
| Itga2 |
G |
A |
13: 115,007,032 (GRCm39) |
S432L |
possibly damaging |
Het |
| Izumo1 |
A |
G |
7: 45,276,621 (GRCm39) |
T395A |
probably benign |
Het |
| Kcnd2 |
G |
A |
6: 21,727,225 (GRCm39) |
V593M |
possibly damaging |
Het |
| Kprp |
T |
C |
3: 92,731,989 (GRCm39) |
S354G |
probably damaging |
Het |
| Krt72 |
T |
C |
15: 101,694,443 (GRCm39) |
K151E |
probably damaging |
Het |
| Letm2 |
A |
T |
8: 26,077,464 (GRCm39) |
|
probably benign |
Het |
| Lipe |
A |
G |
7: 25,097,874 (GRCm39) |
V23A |
possibly damaging |
Het |
| Mcc |
C |
G |
18: 44,652,583 (GRCm39) |
|
probably benign |
Het |
| Mthfd1 |
G |
A |
12: 76,344,363 (GRCm39) |
|
probably benign |
Het |
| Nbeal1 |
C |
A |
1: 60,286,876 (GRCm39) |
N899K |
probably benign |
Het |
| Odad2 |
T |
A |
18: 7,129,593 (GRCm39) |
|
probably benign |
Het |
| Or10ak14 |
T |
C |
4: 118,611,100 (GRCm39) |
I212V |
probably benign |
Het |
| Or4c118 |
T |
C |
2: 88,974,966 (GRCm39) |
I134V |
possibly damaging |
Het |
| Pcdha1 |
T |
A |
18: 37,139,681 (GRCm39) |
W437R |
probably benign |
Het |
| Pcdhga11 |
T |
G |
18: 37,941,528 (GRCm39) |
I643S |
probably benign |
Het |
| Pik3r6 |
T |
A |
11: 68,419,635 (GRCm39) |
Y149N |
probably damaging |
Het |
| Pja2 |
C |
A |
17: 64,615,966 (GRCm39) |
V310L |
probably damaging |
Het |
| Ripor3 |
A |
G |
2: 167,826,358 (GRCm39) |
|
probably benign |
Het |
| Rpa2 |
C |
A |
4: 132,505,125 (GRCm39) |
N251K |
probably damaging |
Het |
| Rttn |
T |
C |
18: 89,029,090 (GRCm39) |
|
probably null |
Het |
| Ryr2 |
C |
T |
13: 11,884,002 (GRCm39) |
|
probably null |
Het |
| Scara3 |
T |
C |
14: 66,168,417 (GRCm39) |
N400S |
probably damaging |
Het |
| Slco1a4 |
G |
A |
6: 141,765,205 (GRCm39) |
Q346* |
probably null |
Het |
| Stk32b |
A |
G |
5: 37,618,792 (GRCm39) |
S229P |
probably damaging |
Het |
| Syde2 |
A |
G |
3: 145,704,508 (GRCm39) |
R487G |
probably benign |
Het |
| Tbc1d2b |
T |
C |
9: 90,104,355 (GRCm39) |
|
probably benign |
Het |
| Ticrr |
T |
C |
7: 79,317,654 (GRCm39) |
V396A |
probably benign |
Het |
| Trrap |
T |
C |
5: 144,719,003 (GRCm39) |
|
probably benign |
Het |
| Vps13a |
A |
T |
19: 16,646,054 (GRCm39) |
H1994Q |
probably damaging |
Het |
| Wdr36 |
T |
G |
18: 32,997,802 (GRCm39) |
V820G |
possibly damaging |
Het |
| Wdr83 |
G |
A |
8: 85,806,456 (GRCm39) |
T114I |
possibly damaging |
Het |
| Zfc3h1 |
A |
G |
10: 115,252,658 (GRCm39) |
K1324E |
probably benign |
Het |
|
| Other mutations in Slc8b1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00958:Slc8b1
|
APN |
5 |
120,671,049 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01111:Slc8b1
|
APN |
5 |
120,671,000 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02186:Slc8b1
|
APN |
5 |
120,665,928 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02448:Slc8b1
|
APN |
5 |
120,663,856 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02501:Slc8b1
|
APN |
5 |
120,658,918 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03380:Slc8b1
|
APN |
5 |
120,657,800 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0062:Slc8b1
|
UTSW |
5 |
120,659,928 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0082:Slc8b1
|
UTSW |
5 |
120,662,265 (GRCm39) |
unclassified |
probably benign |
|
|
R0532:Slc8b1
|
UTSW |
5 |
120,657,736 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0550:Slc8b1
|
UTSW |
5 |
120,669,220 (GRCm39) |
splice site |
probably benign |
|
|
R0751:Slc8b1
|
UTSW |
5 |
120,662,260 (GRCm39) |
unclassified |
probably benign |
|
|
R1667:Slc8b1
|
UTSW |
5 |
120,659,147 (GRCm39) |
missense |
probably benign |
0.39 |
|
R1710:Slc8b1
|
UTSW |
5 |
120,657,717 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1731:Slc8b1
|
UTSW |
5 |
120,659,180 (GRCm39) |
missense |
probably benign |
0.12 |
|
R1865:Slc8b1
|
UTSW |
5 |
120,667,717 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2829:Slc8b1
|
UTSW |
5 |
120,662,078 (GRCm39) |
missense |
probably benign |
0.22 |
|
R4544:Slc8b1
|
UTSW |
5 |
120,669,218 (GRCm39) |
splice site |
probably null |
|
|
R4553:Slc8b1
|
UTSW |
5 |
120,667,663 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4976:Slc8b1
|
UTSW |
5 |
120,663,740 (GRCm39) |
nonsense |
probably null |
|
|
R4977:Slc8b1
|
UTSW |
5 |
120,662,352 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
R5690:Slc8b1
|
UTSW |
5 |
120,651,270 (GRCm39) |
nonsense |
probably null |
|
|
R5812:Slc8b1
|
UTSW |
5 |
120,651,403 (GRCm39) |
splice site |
probably null |
|
|
R6030:Slc8b1
|
UTSW |
5 |
120,657,985 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6030:Slc8b1
|
UTSW |
5 |
120,657,985 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6107:Slc8b1
|
UTSW |
5 |
120,667,665 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6411:Slc8b1
|
UTSW |
5 |
120,659,191 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6486:Slc8b1
|
UTSW |
5 |
120,671,067 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6542:Slc8b1
|
UTSW |
5 |
120,667,582 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6550:Slc8b1
|
UTSW |
5 |
120,662,082 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6992:Slc8b1
|
UTSW |
5 |
120,665,880 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7672:Slc8b1
|
UTSW |
5 |
120,671,100 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8056:Slc8b1
|
UTSW |
5 |
120,658,682 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8444:Slc8b1
|
UTSW |
5 |
120,651,203 (GRCm39) |
start gained |
probably benign |
|
|
R9103:Slc8b1
|
UTSW |
5 |
120,670,939 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9106:Slc8b1
|
UTSW |
5 |
120,668,416 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9166:Slc8b1
|
UTSW |
5 |
120,662,096 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9565:Slc8b1
|
UTSW |
5 |
120,665,865 (GRCm39) |
missense |
probably benign |
0.01 |
|
| Protein Function and Prediction |
Slc24a6 encodes NCKX6, a member of the potassium-dependent sodium/calcium exchangers that maintain cellular calcium homeostasis through the electrogenic countertransport of 4 sodium ions for 1 calcium ion and 1 potassium ion (1). Slc24a6 encodes two alternatively spliced transcripts that encode proteins of different lengths. The shorter isoform differs from the full-length at the C-terminus (1). Examination of the function of the two isoforms found that the short isoform of mouse NCKX6 exhibited potassium-dependent sodium/calcium exchange activity, whereas the full-length isoform did not (1). Overexpression of Slc24a6 results in an increase in mitochondrial Na(+)-dependent Ca(2+) efflux, while siRNA-mediated knockdown of Slc24a6 results in reduced Na(+)-dependent Ca(2+) efflux (2).
|
| Expression/Localization |
Northern blot analysis determined that Slc24a6 is ubiquitously expressed in rat and mouse (1). The short isoform of NCKX6 is expressed at the plasma membrane, while the longer isoform is retained within the endoplasmic reticulum (1). Another study determined that NCKX6 localized to the mitochondria (2).
|
| References |
2. Palty, R., Silverman, W. F., Hershfinkel, M., Caporale, T., Sensi, S. L., Parnis, J., Nolte, C., Fishman, D., Shoshan-Barmatz, V., Herrmann, S., Khananshvili, D., and Sekler, I. (2010) NCLX is an Essential Component of Mitochondrial Na+/Ca2+ Exchange. Proc Natl Acad Sci U S A. 107, 436-441. |
| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation