Incidental Mutation 'R4428:Scn8a'
ID 328291
Institutional Source Beutler Lab
Gene Symbol Scn8a
Ensembl Gene ENSMUSG00000023033
Gene Name sodium channel, voltage-gated, type VIII, alpha
Synonyms nmf335, nmf58, NMF335, C630029C19Rik, nur14, mnd2, seal, mnd-2, nmf2, med, ataxia 3, NaCh6, Nav1.6, motor end-plate disease
MMRRC Submission 041698-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.790) question?
Stock # R4428 (G1)
Quality Score 225
Status Validated
Chromosome 15
Chromosomal Location 100767739-100943819 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 100881784 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 617 (Y617C)
Ref Sequence ENSEMBL: ENSMUSP00000144371 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000082209] [ENSMUST00000108908] [ENSMUST00000108909] [ENSMUST00000108910] [ENSMUST00000200963] [ENSMUST00000201518] [ENSMUST00000201549] [ENSMUST00000202702]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000082209
AA Change: Y617C

PolyPhen 2 Score 0.024 (Sensitivity: 0.95; Specificity: 0.81)
SMART Domains Protein: ENSMUSP00000080842
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 131 422 7.4e-82 PFAM
low complexity region 423 452 N/A INTRINSIC
Pfam:Na_trans_cytopl 499 700 3.5e-72 PFAM
low complexity region 701 712 N/A INTRINSIC
Pfam:Ion_trans 750 985 2.2e-57 PFAM
Pfam:Na_trans_assoc 989 1191 2e-59 PFAM
Pfam:Ion_trans 1195 1472 6.2e-69 PFAM
Pfam:Ion_trans 1519 1775 1.2e-56 PFAM
IQ 1892 1914 1.2e-4 SMART
low complexity region 1953 1972 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000108908
AA Change: Y617C

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000104536
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 72 322 1.9e-76 PFAM
low complexity region 367 378 N/A INTRINSIC
Pfam:Ion_trans 451 640 1.1e-47 PFAM
Pfam:Na_trans_assoc 655 872 1.9e-71 PFAM
Pfam:Ion_trans 898 1127 4.4e-59 PFAM
PDB:1BYY|A 1129 1181 7e-30 PDB
Pfam:Ion_trans 1220 1429 1.9e-51 PFAM
Pfam:PKD_channel 1281 1436 5.6e-7 PFAM
IQ 1558 1580 1.2e-4 SMART
low complexity region 1619 1638 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000108909
AA Change: Y617C

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000104537
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 72 322 2.2e-76 PFAM
low complexity region 335 364 N/A INTRINSIC
Pfam:DUF3451 390 616 8.7e-70 PFAM
Pfam:Ion_trans 697 886 1.3e-47 PFAM
Pfam:Na_trans_assoc 901 1118 2.3e-71 PFAM
Pfam:Ion_trans 1144 1186 9.7e-10 PFAM
Pfam:Ion_trans 1182 1332 1.7e-31 PFAM
PDB:1BYY|A 1334 1386 2e-29 PDB
Pfam:Ion_trans 1425 1634 2.3e-51 PFAM
Pfam:PKD_channel 1486 1641 6.6e-7 PFAM
IQ 1763 1785 1.2e-4 SMART
low complexity region 1824 1843 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000108910
AA Change: Y617C

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000104538
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 160 410 2.5e-76 PFAM
low complexity region 423 452 N/A INTRINSIC
Pfam:DUF3451 478 704 9.6e-70 PFAM
Pfam:Ion_trans 785 974 1.4e-47 PFAM
Pfam:Na_trans_assoc 989 1206 2.5e-71 PFAM
Pfam:Ion_trans 1232 1461 5.7e-59 PFAM
PDB:1BYY|A 1463 1515 4e-29 PDB
Pfam:Ion_trans 1554 1763 2.5e-51 PFAM
Pfam:PKD_channel 1615 1770 7.1e-7 PFAM
IQ 1892 1914 1.2e-4 SMART
low complexity region 1953 1972 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000200963
AA Change: Y617C

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000144371
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 131 422 4.1e-80 PFAM
low complexity region 423 452 N/A INTRINSIC
Pfam:Na_trans_cytopl 499 700 2.5e-69 PFAM
low complexity region 701 712 N/A INTRINSIC
Pfam:Ion_trans 750 985 1.2e-55 PFAM
Pfam:Na_trans_assoc 989 1191 9.1e-57 PFAM
Pfam:Ion_trans 1195 1274 7.6e-16 PFAM
Pfam:Ion_trans 1270 1431 2.6e-33 PFAM
Pfam:Ion_trans 1478 1734 6.5e-55 PFAM
IQ 1851 1873 6e-7 SMART
low complexity region 1912 1931 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000201518
AA Change: Y617C

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000143879
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 131 422 8.8e-81 PFAM
low complexity region 423 452 N/A INTRINSIC
Pfam:Na_trans_cytopl 499 700 6.7e-70 PFAM
low complexity region 701 712 N/A INTRINSIC
Pfam:Ion_trans 750 804 5.3e-9 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000201549
AA Change: Y617C

PolyPhen 2 Score 0.024 (Sensitivity: 0.95; Specificity: 0.81)
SMART Domains Protein: ENSMUSP00000144013
Gene: ENSMUSG00000023033
AA Change: Y617C

DomainStartEndE-ValueType
Pfam:Ion_trans 131 422 7.4e-82 PFAM
low complexity region 423 452 N/A INTRINSIC
Pfam:Na_trans_cytopl 499 700 3.5e-72 PFAM
low complexity region 701 712 N/A INTRINSIC
Pfam:Ion_trans 750 985 2.2e-57 PFAM
Pfam:Na_trans_assoc 989 1191 2e-59 PFAM
Pfam:Ion_trans 1195 1472 6.2e-69 PFAM
Pfam:Ion_trans 1519 1775 1.2e-56 PFAM
IQ 1892 1914 1.2e-4 SMART
low complexity region 1953 1972 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000202702
AA Change: Y467C

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000143876
Gene: ENSMUSG00000023033
AA Change: Y467C

DomainStartEndE-ValueType
Pfam:Ion_trans 1 272 7.9e-75 PFAM
low complexity region 273 302 N/A INTRINSIC
Pfam:Na_trans_cytopl 349 539 9.4e-67 PFAM
Meta Mutation Damage Score 0.1180 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 20x: 95.5%
Validation Efficiency 100% (46/46)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with mental retardation, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
PHENOTYPE: Spontaneous mutant homozygotes have ataxia, dystonia, muscular atrophy, progressive paralysis, Purkinje cell loss, in some cases severe head-tossing and for severe alleles, juvenile lethality. A mild, semidominant ENU allele causes deafness of variable penetrance and severity and mild tremor. [provided by MGI curators]
Allele List at MGI

 All alleles(22) : Targeted, knock-out(1) Targeted, other(1) Gene trapped(6) Transgenic(1) Spontaneous(5) Chemically induced(8)

Other mutations in this stock
Total: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
0610040J01Rik G T 5: 64,056,182 (GRCm39) probably benign Het
Abcc1 T A 16: 14,263,164 (GRCm39) V708E probably damaging Het
Bag4 C T 8: 26,259,516 (GRCm39) A228T probably benign Het
Ccdc18 A G 5: 108,283,943 (GRCm39) Y82C probably benign Het
Cd82 T C 2: 93,250,214 (GRCm39) Y266C probably damaging Het
Chrna4 A G 2: 180,670,413 (GRCm39) S448P probably damaging Het
Cldn8 A C 16: 88,359,619 (GRCm39) M102R probably damaging Het
Cmpk1 T C 4: 114,820,559 (GRCm39) E180G probably benign Het
Dock8 T C 19: 25,177,863 (GRCm39) I2066T probably damaging Het
Dock8 T C 19: 25,042,754 (GRCm39) V112A probably benign Het
Fgf3 T C 7: 144,394,444 (GRCm39) V86A probably damaging Het
Frem2 A G 3: 53,561,759 (GRCm39) I916T probably benign Het
Gsk3b T A 16: 38,014,298 (GRCm39) L252Q probably damaging Het
Kif18a A G 2: 109,118,466 (GRCm39) T94A probably damaging Het
Klhdc1 T A 12: 69,315,000 (GRCm39) probably benign Het
Klhl25 T A 7: 75,515,162 (GRCm39) F23I probably damaging Het
Mapk7 T C 11: 61,380,055 (GRCm39) D701G possibly damaging Het
Mbd5 A T 2: 49,169,776 (GRCm39) Q47L possibly damaging Het
Nrcam A G 12: 44,623,558 (GRCm39) D1049G possibly damaging Het
Olfml2a G T 2: 38,831,755 (GRCm39) M111I probably damaging Het
Or3a1c T C 11: 74,046,025 (GRCm39) F15S probably damaging Het
Pld2 A T 11: 70,432,160 (GRCm39) H93L probably damaging Het
Pomgnt2 T C 9: 121,811,320 (GRCm39) E487G possibly damaging Het
Psg17 G T 7: 18,550,717 (GRCm39) N379K probably benign Het
Rfk T A 19: 17,375,959 (GRCm39) H84Q possibly damaging Het
Sema3d T C 5: 12,498,087 (GRCm39) F31S probably benign Het
Shq1 T C 6: 100,647,889 (GRCm39) Y45C probably damaging Het
Siglecg C T 7: 43,067,350 (GRCm39) P639L possibly damaging Het
Skp2 A T 15: 9,117,034 (GRCm39) N325K probably benign Het
Sost G A 11: 101,857,670 (GRCm39) P44S probably damaging Het
Sp8 T A 12: 118,812,938 (GRCm39) S264R possibly damaging Het
Sun1 T C 5: 139,220,230 (GRCm39) probably benign Het
Tardbp A G 4: 148,709,659 (GRCm39) V54A possibly damaging Het
Tert T A 13: 73,775,594 (GRCm39) F115Y probably damaging Het
Tmem181a T A 17: 6,346,061 (GRCm39) L185H probably damaging Het
Tmem68 A T 4: 3,569,534 (GRCm39) I52K probably benign Het
Trhde A T 10: 114,339,028 (GRCm39) L594Q probably damaging Het
Umps A C 16: 33,781,956 (GRCm39) V322G probably damaging Het
Vmn2r109 T C 17: 20,773,286 (GRCm39) D445G probably benign Het
Vmn2r22 T C 6: 123,614,817 (GRCm39) T258A possibly damaging Het
Vmn2r4 C T 3: 64,322,590 (GRCm39) G43E probably damaging Het
Other mutations in Scn8a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00230:Scn8a APN 15 100,853,413 (GRCm39) unclassified probably benign
IGL00979:Scn8a APN 15 100,853,287 (GRCm39) unclassified probably benign
IGL01339:Scn8a APN 15 100,930,082 (GRCm39) missense probably benign
IGL01992:Scn8a APN 15 100,866,938 (GRCm39) missense probably damaging 1.00
IGL02215:Scn8a APN 15 100,927,453 (GRCm39) splice site probably null
IGL02311:Scn8a APN 15 100,911,164 (GRCm39) missense probably damaging 0.97
IGL02404:Scn8a APN 15 100,937,611 (GRCm39) missense probably damaging 1.00
IGL02652:Scn8a APN 15 100,911,357 (GRCm39) missense probably damaging 0.98
IGL02690:Scn8a APN 15 100,868,135 (GRCm39) missense probably damaging 1.00
IGL02704:Scn8a APN 15 100,905,943 (GRCm39) missense possibly damaging 0.94
IGL03084:Scn8a APN 15 100,915,053 (GRCm39) missense probably damaging 1.00
IGL03108:Scn8a APN 15 100,872,496 (GRCm39) missense probably benign
IGL03224:Scn8a APN 15 100,933,520 (GRCm39) missense probably damaging 1.00
dan UTSW 15 100,933,505 (GRCm39) nonsense probably null
nymph UTSW 15 100,933,527 (GRCm39) missense probably damaging 1.00
Tremord UTSW 15 100,911,385 (GRCm39) missense probably damaging 1.00
3-1:Scn8a UTSW 15 100,937,820 (GRCm39) missense probably benign 0.04
PIT4280001:Scn8a UTSW 15 100,855,370 (GRCm39) missense probably damaging 1.00
PIT4508001:Scn8a UTSW 15 100,927,573 (GRCm39) missense probably damaging 0.98
R0010:Scn8a UTSW 15 100,911,454 (GRCm39) missense probably damaging 1.00
R0010:Scn8a UTSW 15 100,911,454 (GRCm39) missense probably damaging 1.00
R0254:Scn8a UTSW 15 100,916,245 (GRCm39) missense probably damaging 1.00
R0412:Scn8a UTSW 15 100,906,187 (GRCm39) splice site probably benign
R0538:Scn8a UTSW 15 100,933,505 (GRCm39) nonsense probably null
R0539:Scn8a UTSW 15 100,914,449 (GRCm39) missense probably damaging 1.00
R0631:Scn8a UTSW 15 100,933,418 (GRCm39) missense probably damaging 1.00
R0726:Scn8a UTSW 15 100,870,711 (GRCm39) missense probably damaging 1.00
R0945:Scn8a UTSW 15 100,913,668 (GRCm39) missense possibly damaging 0.54
R0967:Scn8a UTSW 15 100,933,527 (GRCm39) missense probably damaging 1.00
R1164:Scn8a UTSW 15 100,938,043 (GRCm39) missense probably benign 0.06
R1283:Scn8a UTSW 15 100,867,052 (GRCm39) missense possibly damaging 0.82
R1368:Scn8a UTSW 15 100,933,422 (GRCm39) missense probably damaging 1.00
R1633:Scn8a UTSW 15 100,927,696 (GRCm39) missense probably benign 0.01
R1669:Scn8a UTSW 15 100,909,001 (GRCm39) missense probably damaging 1.00
R1694:Scn8a UTSW 15 100,853,409 (GRCm39) nonsense probably null
R1735:Scn8a UTSW 15 100,913,742 (GRCm39) missense possibly damaging 0.94
R1773:Scn8a UTSW 15 100,937,496 (GRCm39) missense probably damaging 0.97
R1940:Scn8a UTSW 15 100,868,085 (GRCm39) missense probably benign 0.22
R1996:Scn8a UTSW 15 100,922,260 (GRCm39) missense probably damaging 1.00
R2107:Scn8a UTSW 15 100,916,244 (GRCm39) missense probably damaging 0.99
R2251:Scn8a UTSW 15 100,914,987 (GRCm39) missense probably benign 0.02
R2516:Scn8a UTSW 15 100,867,043 (GRCm39) missense probably benign 0.05
R2917:Scn8a UTSW 15 100,937,613 (GRCm39) missense probably damaging 1.00
R3417:Scn8a UTSW 15 100,869,549 (GRCm39) splice site probably benign
R3896:Scn8a UTSW 15 100,933,379 (GRCm39) missense probably benign
R4024:Scn8a UTSW 15 100,937,674 (GRCm39) missense probably damaging 1.00
R4050:Scn8a UTSW 15 100,911,294 (GRCm39) nonsense probably null
R4193:Scn8a UTSW 15 100,869,484 (GRCm39) missense probably damaging 1.00
R4212:Scn8a UTSW 15 100,854,954 (GRCm39) missense possibly damaging 0.88
R4358:Scn8a UTSW 15 100,838,014 (GRCm39) missense probably benign 0.00
R4396:Scn8a UTSW 15 100,870,711 (GRCm39) missense probably damaging 1.00
R4452:Scn8a UTSW 15 100,854,972 (GRCm39) missense possibly damaging 0.95
R4631:Scn8a UTSW 15 100,914,384 (GRCm39) nonsense probably null
R4693:Scn8a UTSW 15 100,913,572 (GRCm39) missense probably damaging 1.00
R4765:Scn8a UTSW 15 100,938,352 (GRCm39) missense probably benign 0.07
R4777:Scn8a UTSW 15 100,913,832 (GRCm39) missense probably damaging 1.00
R4949:Scn8a UTSW 15 100,927,663 (GRCm39) missense probably damaging 1.00
R4997:Scn8a UTSW 15 100,854,935 (GRCm39) missense probably damaging 1.00
R5246:Scn8a UTSW 15 100,908,938 (GRCm39) missense probably damaging 1.00
R5566:Scn8a UTSW 15 100,872,415 (GRCm39) missense probably damaging 1.00
R5875:Scn8a UTSW 15 100,870,703 (GRCm39) nonsense probably null
R6031:Scn8a UTSW 15 100,881,865 (GRCm39) missense probably damaging 1.00
R6031:Scn8a UTSW 15 100,881,865 (GRCm39) missense probably damaging 1.00
R6057:Scn8a UTSW 15 100,872,548 (GRCm39) missense possibly damaging 0.94
R6114:Scn8a UTSW 15 100,938,477 (GRCm39) missense probably damaging 0.99
R6362:Scn8a UTSW 15 100,837,996 (GRCm39) splice site probably null
R6535:Scn8a UTSW 15 100,857,588 (GRCm39) intron probably benign
R6677:Scn8a UTSW 15 100,866,953 (GRCm39) missense probably damaging 1.00
R6687:Scn8a UTSW 15 100,872,508 (GRCm39) missense probably benign 0.12
R6701:Scn8a UTSW 15 100,937,977 (GRCm39) missense probably damaging 1.00
R6719:Scn8a UTSW 15 100,908,896 (GRCm39) critical splice acceptor site probably null
R6739:Scn8a UTSW 15 100,913,836 (GRCm39) missense possibly damaging 0.82
R6769:Scn8a UTSW 15 100,933,445 (GRCm39) missense probably benign
R6786:Scn8a UTSW 15 100,930,096 (GRCm39) missense probably benign 0.00
R6849:Scn8a UTSW 15 100,853,468 (GRCm39) splice site probably null
R7108:Scn8a UTSW 15 100,937,659 (GRCm39) missense probably benign 0.01
R7215:Scn8a UTSW 15 100,927,711 (GRCm39) missense possibly damaging 0.80
R7217:Scn8a UTSW 15 100,868,108 (GRCm39) missense probably benign 0.00
R7219:Scn8a UTSW 15 100,866,984 (GRCm39) missense probably damaging 1.00
R7356:Scn8a UTSW 15 100,855,460 (GRCm39) missense probably damaging 1.00
R7479:Scn8a UTSW 15 100,853,358 (GRCm39) missense probably damaging 0.99
R7816:Scn8a UTSW 15 100,908,917 (GRCm39) missense possibly damaging 0.63
R7985:Scn8a UTSW 15 100,914,843 (GRCm39) splice site probably null
R8112:Scn8a UTSW 15 100,927,718 (GRCm39) missense probably benign 0.27
R8263:Scn8a UTSW 15 100,881,736 (GRCm39) missense probably damaging 1.00
R8305:Scn8a UTSW 15 100,938,387 (GRCm39) missense probably benign 0.01
R8489:Scn8a UTSW 15 100,867,014 (GRCm39) missense probably damaging 1.00
R8983:Scn8a UTSW 15 100,900,030 (GRCm39) missense possibly damaging 0.81
R9034:Scn8a UTSW 15 100,927,642 (GRCm39) missense probably damaging 0.98
R9050:Scn8a UTSW 15 100,906,161 (GRCm39) missense possibly damaging 0.80
R9240:Scn8a UTSW 15 100,915,068 (GRCm39) nonsense probably null
R9249:Scn8a UTSW 15 100,914,456 (GRCm39) missense probably benign 0.00
R9462:Scn8a UTSW 15 100,930,159 (GRCm39) missense
R9599:Scn8a UTSW 15 100,911,172 (GRCm39) missense probably damaging 1.00
R9609:Scn8a UTSW 15 100,834,407 (GRCm39) missense possibly damaging 0.91
R9653:Scn8a UTSW 15 100,937,947 (GRCm39) missense probably damaging 1.00
R9794:Scn8a UTSW 15 100,933,332 (GRCm39) missense probably benign 0.00
X0066:Scn8a UTSW 15 100,937,962 (GRCm39) missense probably damaging 1.00
X0066:Scn8a UTSW 15 100,937,961 (GRCm39) missense probably damaging 1.00
Z1176:Scn8a UTSW 15 100,931,399 (GRCm39) missense probably damaging 1.00
Z1177:Scn8a UTSW 15 100,938,103 (GRCm39) missense probably benign 0.00
Predicted Primers PCR Primer
(F):5'- TCCCACAGGACTTTCTGGGT -3'
(R):5'- ACACTGTCTGTAGCTGCCTT -3'

Sequencing Primer
(F):5'- TGCTCAGCATCCCAGGCTC -3'
(R):5'- GCCTTATCTATTTTCACCTCAGGCAG -3'
Posted On 2015-07-07