Mutagenetix > Incidental Mutations

Incidental Mutation 'R4631:Scn8a'

349225

Institutional Source

Beutler Lab

Gene Symbol

Scn8a

Ensembl Gene

ENSMUSG00000023033

Gene Name

sodium channel, voltage-gated, type VIII, alpha

Synonyms

mnd2, C630029C19Rik, nmf58, NMF335, mnd-2, seal, motor end-plate disease, nur14, Nav1.6, med, ataxia 3, nmf2, nmf335, NaCh6

MMRRC Submission

041896-MU

Accession Numbers

Genbank: NM_001077499, NM_011323; MGI: 103169

Is this an essential gene?

Probably essential (E-score: 0.788) question?

Stock #

R4631 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

100869858-101045938 bp(+) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

C to A at 101016503 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Stop codon at position 1130 (S1130*)

Ref Sequence

ENSEMBL: ENSMUSP00000144013 (fasta)

Gene Model

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

Predicted Effect

probably null
Transcript: ENSMUST00000082209
AA Change: S1130*

SMART Domains

Protein: ENSMUSP00000080842
Gene: ENSMUSG00000023033
AA Change: S1130*

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

probably null
Transcript: ENSMUST00000108908
AA Change: S1130*

SMART Domains

Protein: ENSMUSP00000104536
Gene: ENSMUSG00000023033
AA Change: S1130*

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

probably null
Transcript: ENSMUST00000108909
AA Change: S1140*

SMART Domains

Protein: ENSMUSP00000104537
Gene: ENSMUSG00000023033
AA Change: S1140*

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

probably null
Transcript: ENSMUST00000108910
AA Change: S1130*

SMART Domains

Protein: ENSMUSP00000104538
Gene: ENSMUSG00000023033
AA Change: S1130*

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 null
Transcript: ENSMUST00000200963
AA Change: S1130*

SMART Domains

Protein: ENSMUSP00000144371
Gene: ENSMUSG00000023033
AA Change: S1130*

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 null
Transcript: ENSMUST00000201549
AA Change: S1130*

SMART Domains

Protein: ENSMUSP00000144013
Gene: ENSMUSG00000023033
AA Change: S1130*

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

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.0%

Validation Efficiency

100% (84/84)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700017B05Rik	A	T	9: 57,257,987	L368Q	probably damaging	Het
Abcc2	C	T	19: 43,814,707	P661S	possibly damaging	Het
Adgre4	T	G	17: 55,814,305	M457R	probably null	Het
Ank	C	A	15: 27,467,090	F29L	probably benign	Het
Arhgap20	T	C	9: 51,840,353		probably benign	Het
Atf6	T	C	1: 170,747,197		probably null	Het
Bod1l	A	G	5: 41,817,735	F2079L	probably damaging	Het
Cd163	T	C	6: 124,329,086	*1122Q	probably null	Het
Ces2g	T	C	8: 104,967,462		probably null	Het
Cntnap3	A	G	13: 64,778,883	Y558H	probably benign	Het
Ctsm	T	A	13: 61,537,696	S301C	probably null	Het
Dlc1	A	C	8: 36,937,558		probably null	Het
Dlg2	A	T	7: 92,088,614	I435F	probably damaging	Het
Dnah5	T	C	15: 28,401,953	V3420A	probably damaging	Het
Dnah5	T	A	15: 28,419,994	Y3813N	probably damaging	Het
Dnajc13	A	G	9: 104,190,417	M1181T	probably damaging	Het
Drc3	C	A	11: 60,364,908	T107N	probably benign	Het
Dydc2	T	C	14: 41,049,329	E131G	probably benign	Het
Eif5b	T	C	1: 38,041,747	V723A	probably damaging	Het
Fndc9	C	A	11: 46,237,848	H65N	possibly damaging	Het
Fzd1	A	T	5: 4,755,865	Y572*	probably null	Het
Gm1966	A	G	7: 106,599,523		noncoding transcript	Het
Gm38394	A	T	1: 133,658,744	V285E	probably damaging	Het
Gm5096	G	A	18: 87,756,401	R16H	probably damaging	Het
Gps1	T	A	11: 120,788,239		probably null	Het
Kazn	G	A	4: 142,118,160		probably benign	Het
Kcnd3	C	T	3: 105,658,766	A421V	probably damaging	Het
Kcnip1	T	A	11: 33,992,821		noncoding transcript	Het
Kif19a	A	G	11: 114,784,847	I382V	possibly damaging	Het
Krt1	C	T	15: 101,846,187	G543S	unknown	Het
Malsu1	A	T	6: 49,084,533	E177V	probably damaging	Het
Man2a2	A	G	7: 80,362,463	F649L	probably benign	Het
Map3k11	A	G	19: 5,690,913	I223V	probably benign	Het
Mroh2a	A	G	1: 88,258,664	S64G	probably benign	Het
Myh9	T	G	15: 77,797,028	D164A	probably damaging	Het
Myo16	T	C	8: 10,506,984	I1040T	probably damaging	Het
Myo18b	C	T	5: 112,846,400	A896T	probably damaging	Het
Myocd	G	T	11: 65,178,859	N798K	probably benign	Het
Olfr1206	C	T	2: 88,864,830	T75I	probably benign	Het
Olfr1288	T	A	2: 111,479,563	W260R	probably damaging	Het
Olfr1458	T	A	19: 13,103,272	I11F	probably benign	Het
Olfr156	T	C	4: 43,820,563	D266G	probably benign	Het
Olfr168	G	A	16: 19,530,141	R260*	probably null	Het
Olfr353	T	G	2: 36,890,618	T77P	probably benign	Het
Olfr68	A	T	7: 103,777,475	L290Q	probably damaging	Het
Pcdh18	T	A	3: 49,756,441	I142F	probably damaging	Het
Pcyox1	T	C	6: 86,389,143	D363G	probably benign	Het
Pcyox1	T	C	6: 86,389,230	E334G	possibly damaging	Het
Pgm1	A	G	5: 64,105,947		probably null	Het
Plagl1	T	G	10: 13,127,999		probably benign	Het
Ppp1r9a	A	G	6: 4,906,537	D364G	possibly damaging	Het
Rab2b	T	A	14: 52,266,242	H141L	possibly damaging	Het
Rev3l	A	G	10: 39,828,416	K279E	probably benign	Het
Rnf111	G	T	9: 70,450,396	T607N	probably benign	Het
Selenbp1	A	G	3: 94,944,568	*473W	probably null	Het
Sh3bp4	A	C	1: 89,144,273	D281A	probably damaging	Het
Skint5	T	A	4: 113,629,117		probably null	Het
Slc1a4	A	G	11: 20,308,452	L249P	probably damaging	Het
Slc45a2	T	A	15: 11,012,576	S222T	probably benign	Het
Slc7a4	A	G	16: 17,574,391	F393S	probably damaging	Het
Slc9a2	A	T	1: 40,761,918	D536V	possibly damaging	Het
Stra6	T	A	9: 58,140,832		probably benign	Het
Tmem145	A	G	7: 25,307,825	D156G	probably benign	Het
Tns3	A	C	11: 8,451,119	F1060V	probably benign	Het
Trak1	G	A	9: 121,454,425	R419Q	probably benign	Het
Trappc8	A	G	18: 20,867,808	S273P	probably benign	Het
Trmt11	A	G	10: 30,559,204	S320P	probably benign	Het
Ugt1a6a	A	T	1: 88,139,258	Y262F	probably benign	Het
Vmn1r73	G	A	7: 11,756,831	C192Y	probably benign	Het
Vmn2r103	T	C	17: 19,793,696	I250T	probably benign	Het
Vmn2r25	T	A	6: 123,853,003	D63V	possibly damaging	Het
Vps13b	C	T	15: 35,646,132	H1461Y	possibly damaging	Het
Ythdc2	A	T	18: 44,887,631	E1427D	probably benign	Het
Zbtb26	A	G	2: 37,436,956	F23L	probably benign	Het
Zfp62	T	A	11: 49,217,805	*908R	probably null	Het
Zfp975	A	T	7: 42,662,945	N81K	probably benign	Het
Zkscan16	G	A	4: 58,951,918	V198M	probably damaging	Het

Other mutations in Scn8a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00230:Scn8a	APN	15	100955532	unclassified	probably benign
IGL00979:Scn8a	APN	15	100955406	unclassified	probably benign
IGL01339:Scn8a	APN	15	101032201	missense	probably benign
IGL01992:Scn8a	APN	15	100969057	missense	probably damaging	1.00
IGL02215:Scn8a	APN	15	101029572	splice site	probably null
IGL02311:Scn8a	APN	15	101013283	missense	probably damaging	0.97
IGL02404:Scn8a	APN	15	101039730	missense	probably damaging	1.00
IGL02652:Scn8a	APN	15	101013476	missense	probably damaging	0.98
IGL02690:Scn8a	APN	15	100970254	missense	probably damaging	1.00
IGL02704:Scn8a	APN	15	101008062	missense	possibly damaging	0.94
IGL03084:Scn8a	APN	15	101017172	missense	probably damaging	1.00
IGL03108:Scn8a	APN	15	100974615	missense	probably benign
IGL03224:Scn8a	APN	15	101035639	missense	probably damaging	1.00
dan	UTSW	15	101035624	nonsense	probably null
nymph	UTSW	15	101035646	missense	probably damaging	1.00
Tremord	UTSW	15	101013504	missense	probably damaging	1.00
3-1:Scn8a	UTSW	15	101039939	missense	probably benign	0.04
PIT4280001:Scn8a	UTSW	15	100957489	missense	probably damaging	1.00
PIT4508001:Scn8a	UTSW	15	101029692	missense	probably damaging	0.98
R0010:Scn8a	UTSW	15	101013573	missense	probably damaging	1.00
R0010:Scn8a	UTSW	15	101013573	missense	probably damaging	1.00
R0254:Scn8a	UTSW	15	101018364	missense	probably damaging	1.00
R0412:Scn8a	UTSW	15	101008306	splice site	probably benign
R0538:Scn8a	UTSW	15	101035624	nonsense	probably null
R0539:Scn8a	UTSW	15	101016568	missense	probably damaging	1.00
R0631:Scn8a	UTSW	15	101035537	missense	probably damaging	1.00
R0726:Scn8a	UTSW	15	100972830	missense	probably damaging	1.00
R0945:Scn8a	UTSW	15	101015787	missense	possibly damaging	0.54
R0967:Scn8a	UTSW	15	101035646	missense	probably damaging	1.00
R1164:Scn8a	UTSW	15	101040162	missense	probably benign	0.06
R1283:Scn8a	UTSW	15	100969171	missense	possibly damaging	0.82
R1368:Scn8a	UTSW	15	101035541	missense	probably damaging	1.00
R1633:Scn8a	UTSW	15	101029815	missense	probably benign	0.01
R1669:Scn8a	UTSW	15	101011120	missense	probably damaging	1.00
R1694:Scn8a	UTSW	15	100955528	nonsense	probably null
R1735:Scn8a	UTSW	15	101015861	missense	possibly damaging	0.94
R1773:Scn8a	UTSW	15	101039615	missense	probably damaging	0.97
R1940:Scn8a	UTSW	15	100970204	missense	probably benign	0.22
R1996:Scn8a	UTSW	15	101024379	missense	probably damaging	1.00
R2107:Scn8a	UTSW	15	101018363	missense	probably damaging	0.99
R2251:Scn8a	UTSW	15	101017106	missense	probably benign	0.02
R2516:Scn8a	UTSW	15	100969162	missense	probably benign	0.05
R2917:Scn8a	UTSW	15	101039732	missense	probably damaging	1.00
R3417:Scn8a	UTSW	15	100971668	splice site	probably benign
R3896:Scn8a	UTSW	15	101035498	missense	probably benign
R4024:Scn8a	UTSW	15	101039793	missense	probably damaging	1.00
R4050:Scn8a	UTSW	15	101013413	nonsense	probably null
R4193:Scn8a	UTSW	15	100971603	missense	probably damaging	1.00
R4212:Scn8a	UTSW	15	100957073	missense	possibly damaging	0.88
R4358:Scn8a	UTSW	15	100940133	missense	probably benign	0.00
R4396:Scn8a	UTSW	15	100972830	missense	probably damaging	1.00
R4428:Scn8a	UTSW	15	100983903	missense	probably damaging	1.00
R4452:Scn8a	UTSW	15	100957091	missense	possibly damaging	0.95
R4693:Scn8a	UTSW	15	101015691	missense	probably damaging	1.00
R4765:Scn8a	UTSW	15	101040471	missense	probably benign	0.07
R4777:Scn8a	UTSW	15	101015951	missense	probably damaging	1.00
R4949:Scn8a	UTSW	15	101029782	missense	probably damaging	1.00
R4997:Scn8a	UTSW	15	100957054	missense	probably damaging	1.00
R5246:Scn8a	UTSW	15	101011057	missense	probably damaging	1.00
R5566:Scn8a	UTSW	15	100974534	missense	probably damaging	1.00
R5875:Scn8a	UTSW	15	100972822	nonsense	probably null
R6031:Scn8a	UTSW	15	100983984	missense	probably damaging	1.00
R6031:Scn8a	UTSW	15	100983984	missense	probably damaging	1.00
R6057:Scn8a	UTSW	15	100974667	missense	possibly damaging	0.94
R6114:Scn8a	UTSW	15	101040596	missense	probably damaging	0.99
R6362:Scn8a	UTSW	15	100940115	splice site	probably null
R6535:Scn8a	UTSW	15	100959707	intron	probably benign
R6677:Scn8a	UTSW	15	100969072	missense	probably damaging	1.00
R6687:Scn8a	UTSW	15	100974627	missense	probably benign	0.12
R6701:Scn8a	UTSW	15	101040096	missense	probably damaging	1.00
R6719:Scn8a	UTSW	15	101011015	critical splice acceptor site	probably null
R6739:Scn8a	UTSW	15	101015955	missense	possibly damaging	0.82
R6769:Scn8a	UTSW	15	101035564	missense	probably benign
R6786:Scn8a	UTSW	15	101032215	missense	probably benign	0.00
R6849:Scn8a	UTSW	15	100955587	splice site	probably null
R7108:Scn8a	UTSW	15	101039778	missense	probably benign	0.01
R7215:Scn8a	UTSW	15	101029830	missense	possibly damaging	0.80
R7217:Scn8a	UTSW	15	100970227	missense	probably benign	0.00
R7219:Scn8a	UTSW	15	100969103	missense	probably damaging	1.00
R7356:Scn8a	UTSW	15	100957579	missense	probably damaging	1.00
R7479:Scn8a	UTSW	15	100955477	missense	probably damaging	0.99
R7816:Scn8a	UTSW	15	101011036	missense	possibly damaging	0.63
R7985:Scn8a	UTSW	15	101016962	splice site	probably null
R8112:Scn8a	UTSW	15	101029837	missense	probably benign	0.27
R8263:Scn8a	UTSW	15	100983855	missense	probably damaging	1.00
R8305:Scn8a	UTSW	15	101040506	missense	probably benign	0.01
R8489:Scn8a	UTSW	15	100969133	missense	probably damaging	1.00
X0066:Scn8a	UTSW	15	101040080	missense	probably damaging	1.00
X0066:Scn8a	UTSW	15	101040081	missense	probably damaging	1.00
Z1176:Scn8a	UTSW	15	101033518	missense	probably damaging	1.00
Z1177:Scn8a	UTSW	15	101040222	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- AGCCCTTTAGTTTGTCCCGG -3'
(R):5'- CCTTTCTAATGGCAGTCTGGGG -3'

Sequencing Primer
(F):5'- GCTCTGAATCCACGTGACC -3'
(R):5'- TATATCAGAACTGGGTAAGGGAAATC -3'

Posted On

2015-10-08