Incidental Mutation 'R6670:Slc8a1'
ID 527120
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 044790-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6670 (G1)
Quality Score 225.009
Status Validated
Chromosome 17
Chromosomal Location 81680534-82045806 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 81956883 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Arginine at position 52 (C52R)
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: C52R

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000083725
Gene: ENSMUSG00000054640
AA Change: C52R

DomainStartEndE-ValueType
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 probably damaging
Transcript: ENSMUST00000163123
AA Change: C52R

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000132809
Gene: ENSMUSG00000054640
AA Change: C52R

DomainStartEndE-ValueType
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: C52R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000126373
Gene: ENSMUSG00000054640
AA Change: C52R

DomainStartEndE-ValueType
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
Meta Mutation Damage Score 0.8839 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.7%
  • 20x: 96.6%
Validation Efficiency 100% (38/38)
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: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc2 A G 19: 43,827,850 (GRCm39) 1544 probably benign Het
Acsm3 T A 7: 119,379,978 (GRCm39) probably null Het
AW551984 T C 9: 39,504,292 (GRCm39) D558G probably damaging Het
Bcl9l GTGAACATGAACATGAACATGAAC GTGAACATGAACATGAACATGAACATGAAC 9: 44,418,369 (GRCm39) probably benign Het
Brd8dc A G 18: 34,719,319 (GRCm39) V167A possibly damaging Het
Ccdc12 T G 9: 110,537,595 (GRCm39) probably null Het
Ctsl T C 13: 64,511,916 (GRCm39) probably null Het
Cul1 T A 6: 47,494,068 (GRCm39) D460E probably damaging Het
Dnttip2 T A 3: 122,069,870 (GRCm39) S362T probably damaging Het
Fbxw16 T A 9: 109,267,280 (GRCm39) D317V probably damaging Het
Fbxw9 T A 8: 85,788,839 (GRCm39) N196K possibly damaging Het
Grap A G 11: 61,551,064 (GRCm39) D32G probably damaging Het
Hhatl T C 9: 121,618,137 (GRCm39) D206G probably damaging Het
Hrnr A T 3: 93,239,192 (GRCm39) Q3143H unknown Het
Ighv1-62-1 T C 12: 115,350,529 (GRCm39) Y46C probably damaging Het
Krtap16-3 A T 16: 88,759,540 (GRCm39) Y58N unknown Het
Mef2c A G 13: 83,810,716 (GRCm39) K384R probably damaging Het
Nalcn A G 14: 123,702,084 (GRCm39) Y476H possibly damaging Het
Oxgr1 A T 14: 120,259,669 (GRCm39) N179K probably damaging Het
Polk G A 13: 96,633,138 (GRCm39) Q302* probably null Het
Rab3gap1 T A 1: 127,858,512 (GRCm39) S540R probably benign Het
Samd5 A T 10: 9,504,808 (GRCm39) probably null Het
Sema6d GTGATAC G 2: 124,496,762 (GRCm39) probably benign Het
Slc1a6 C A 10: 78,623,646 (GRCm39) A15D probably benign Het
Sod2 T A 17: 13,227,252 (GRCm39) Y69N possibly damaging Het
Tank T C 2: 61,474,768 (GRCm39) probably null Het
Tbc1d23 A T 16: 57,034,580 (GRCm39) I73N probably benign Het
Tnf A C 17: 35,420,800 (GRCm39) M6R possibly damaging Het
Trmt2a C T 16: 18,068,341 (GRCm39) A16V possibly damaging Het
Ttn A G 2: 76,556,055 (GRCm39) Y21990H probably damaging Het
Uaca C T 9: 60,779,306 (GRCm39) S1231L probably benign Het
Ubr1 A G 2: 120,754,611 (GRCm39) probably null Het
Unc13b A G 4: 43,255,562 (GRCm39) D3849G probably damaging Het
Vmn2r75 T A 7: 85,797,644 (GRCm39) D723V probably damaging Het
Wnt2 C A 6: 18,028,091 (GRCm39) V48L possibly damaging Het
Other mutations in Slc8a1
AlleleSourceChrCoordTypePredicted EffectPPH 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
R5766:Slc8a1 UTSW 17 81,956,390 (GRCm39) missense probably damaging 0.97
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
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'- GTTCCAGATTCTCACCGTCG -3'
(R):5'- GGAGCAGTTGGAAGTCTTATTGTAC -3'

Sequencing Primer
(F):5'- AGATTCTCACCGTCGTCTTGGTG -3'
(R):5'- GTACAACATGCTTCGATTAAGTCTCC -3'
Posted On 2018-07-23