Mutagenetix > Incidental Mutation

Incidental Mutation 'R4949:Scn8a'

383682

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

042546-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.790) question?

Stock #

R4949 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

100767739-100943819 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 100927663 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Aspartic acid at position 1381 (N1381D)

Ref Sequence

ENSEMBL: ENSMUSP00000144013 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000082209] [ENSMUST00000108908] [ENSMUST00000108909] [ENSMUST00000108910] [ENSMUST00000200963] [ENSMUST00000201549]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000082209
AA Change: N1381D

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000080842
Gene: ENSMUSG00000023033
AA Change: N1381D

Domain	Start	End	E-Value	Type
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: ENSMUST00000108908
AA Change: N1381D

PolyPhen 2 Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000104536
Gene: ENSMUSG00000023033
AA Change: N1381D

Domain	Start	End	E-Value	Type
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

possibly damaging
Transcript: ENSMUST00000108909
AA Change: N1391D

PolyPhen 2 Score 0.834 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000104537
Gene: ENSMUSG00000023033
AA Change: N1391D

Domain	Start	End	E-Value	Type
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

possibly damaging
Transcript: ENSMUST00000108910
AA Change: N1381D

PolyPhen 2 Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000104538
Gene: ENSMUSG00000023033
AA Change: N1381D

Domain	Start	End	E-Value	Type
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: N1340D

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000144371
Gene: ENSMUSG00000023033
AA Change: N1340D

Domain	Start	End	E-Value	Type
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

noncoding transcript
Transcript: ENSMUST00000201246

Predicted Effect

probably damaging
Transcript: ENSMUST00000201549
AA Change: N1381D

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000144013
Gene: ENSMUSG00000023033
AA Change: N1381D

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.1%
20x: 91.3%

Validation Efficiency

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: 35 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acox3	T	C	5: 35,769,450 (GRCm39)	V692A	probably benign	Het
Bcl2l13	G	T	6: 120,864,191 (GRCm39)	G382W	probably damaging	Het
Cdhr5	T	A	7: 140,852,557 (GRCm39)	N353I	probably damaging	Het
Chil4	A	G	3: 106,113,408 (GRCm39)	S170P	possibly damaging	Het
Clp1	A	C	2: 84,554,086 (GRCm39)	M361R	possibly damaging	Het
Cylc2	A	G	4: 51,229,804 (GRCm39)	K382R	unknown	Het
Dsg2	T	A	18: 20,723,241 (GRCm39)	D422E	probably damaging	Het
Dync1h1	C	A	12: 110,624,560 (GRCm39)	T3700N	probably damaging	Het
Gm14295	A	C	2: 176,501,469 (GRCm39)	T320P	probably damaging	Het
Ido2	T	G	8: 25,023,970 (GRCm39)		probably null	Het
Ift140	T	A	17: 25,313,639 (GRCm39)	S1357T	probably benign	Het
Insr	T	G	8: 3,235,059 (GRCm39)	E145A	probably benign	Het
Itpripl1	A	G	2: 126,983,327 (GRCm39)	M265T	probably benign	Het
Kcnb1	G	T	2: 166,947,521 (GRCm39)	N442K	probably damaging	Het
Kifc5b	C	A	17: 27,144,488 (GRCm39)	R536S	probably damaging	Het
Klf6	A	T	13: 5,914,947 (GRCm39)	S129C	probably benign	Het
Lpin2	C	G	17: 71,538,334 (GRCm39)	P327A	probably damaging	Het
Lsm1	T	C	8: 26,292,065 (GRCm39)	V114A	probably benign	Het
Map7d1	C	T	4: 126,128,846 (GRCm39)	W218*	probably null	Het
N4bp2	T	A	5: 65,979,142 (GRCm39)		probably null	Het
Nt5el	T	A	13: 105,246,214 (GRCm39)	S258R	probably damaging	Het
Rheb	A	T	5: 25,008,729 (GRCm39)	I163K	possibly damaging	Het
Rph3a	T	C	5: 121,101,897 (GRCm39)	D113G	probably damaging	Het
Sdsl	T	A	5: 120,597,870 (GRCm39)	N208Y	possibly damaging	Het
Serpinb9e	A	G	13: 33,435,591 (GRCm39)	N8S	possibly damaging	Het
Sox18	G	A	2: 181,313,017 (GRCm39)	Q100*	probably null	Het
Taar8b	C	T	10: 23,967,825 (GRCm39)	C123Y	probably damaging	Het
Tas2r124	A	G	6: 132,731,858 (GRCm39)	I56V	possibly damaging	Het
Tes	C	A	6: 17,100,359 (GRCm39)	H331N	probably benign	Het
Tmbim1	T	G	1: 74,334,524 (GRCm39)	D12A	probably damaging	Het
Tmprss4	T	C	9: 45,086,841 (GRCm39)	I307V	possibly damaging	Het
Ttll1	A	T	15: 83,386,374 (GRCm39)	M77K	probably null	Het
Ttpal	G	A	2: 163,455,671 (GRCm39)	R220Q	probably damaging	Het
Vmn1r230	T	A	17: 21,067,625 (GRCm39)	H271Q	probably benign	Het
Vmn2r32	A	G	7: 7,467,083 (GRCm39)	I815T	probably benign	Het

Other mutations in Scn8a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R4428:Scn8a	UTSW	15	100,881,784 (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
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	100,937,961 (GRCm39)	missense	probably damaging	1.00
X0066:Scn8a	UTSW	15	100,937,962 (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'- TCATGAACGTGCTGCTGGTG -3'
(R):5'- CACCAAGATGCTGCCAAGAG -3'

Sequencing Primer
(F):5'- CTGGTGTGTCTCATCTTCTGGC -3'
(R):5'- GCTGATTTGGGGAGCATAACG -3'

Posted On

2016-04-27