Mutagenetix > Incidental Mutation

Incidental Mutation 'R1735:Scn8a'

199678

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

039767-MU

Accession Numbers

Genbank: NM_001077499, NM_011323; MGI: 103169

Essential gene?

Possibly essential (E-score: 0.749) question?

Stock #

R1735 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

100869858-101045938 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 101015861 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Aspartic acid at position 1045 (N1045D)

Ref Sequence

ENSEMBL: ENSMUSP00000144371 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000082209] [ENSMUST00000108908] [ENSMUST00000108909] [ENSMUST00000108910] [ENSMUST00000200963] [ENSMUST00000201518] [ENSMUST00000201549]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000082209
AA Change: N1045D

PolyPhen 2 Score 0.367 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000080842
Gene: ENSMUSG00000023033
AA Change: N1045D

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 benign
Transcript: ENSMUST00000108908
AA Change: N1045D

PolyPhen 2 Score 0.028 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000104536
Gene: ENSMUSG00000023033
AA Change: N1045D

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 benign
Transcript: ENSMUST00000108909
AA Change: N1055D

PolyPhen 2 Score 0.286 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000104537
Gene: ENSMUSG00000023033
AA Change: N1055D

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 benign
Transcript: ENSMUST00000108910
AA Change: N1045D

PolyPhen 2 Score 0.065 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000104538
Gene: ENSMUSG00000023033
AA Change: N1045D

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

possibly damaging
Transcript: ENSMUST00000200963
AA Change: N1045D

PolyPhen 2 Score 0.941 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000144371
Gene: ENSMUSG00000023033
AA Change: N1045D

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 benign
Transcript: ENSMUST00000201518

SMART Domains

Protein: ENSMUSP00000143879
Gene: ENSMUSG00000023033

Domain	Start	End	E-Value	Type
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: N1045D

PolyPhen 2 Score 0.367 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000144013
Gene: ENSMUSG00000023033
AA Change: N1045D

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: 97.6%
3x: 97.0%
10x: 95.3%
20x: 92.1%

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9230110C19Rik	A	C	9: 8,027,265	S91A	probably benign	Het
Acot5	A	T	12: 84,075,487	I282F	probably benign	Het
Adam19	C	A	11: 46,138,917	Q730K	probably benign	Het
Adgrv1	A	G	13: 81,487,947	V3481A	possibly damaging	Het
Akr1c20	T	C	13: 4,487,208	D316G	probably benign	Het
Ap3b1	G	A	13: 94,493,717	V827I	unknown	Het
Aph1a	T	A	3: 95,895,509	D140E	probably damaging	Het
Arhgef19	G	T	4: 141,249,618	V502L	possibly damaging	Het
Arl9	T	C	5: 77,006,626	F67S	probably damaging	Het
B430305J03Rik	G	A	3: 61,363,940		probably benign	Het
B4galnt2	A	G	11: 95,890,983	F119L	probably damaging	Het
Bcap29	T	A	12: 31,630,840	N49I	probably damaging	Het
C77080	G	T	4: 129,223,577	S476R	probably damaging	Het
Capn11	T	A	17: 45,632,401	K616*	probably null	Het
Cdh12	T	A	15: 21,520,366	Y306N	probably damaging	Het
Cep350	T	A	1: 155,953,214	N315Y	probably damaging	Het
Cited2	C	A	10: 17,724,046	P34Q	probably damaging	Het
Cmya5	A	T	13: 93,089,789	D2930E	probably benign	Het
Cog3	T	A	14: 75,729,321	K470*	probably null	Het
Commd10	A	G	18: 46,990,485	T136A	probably benign	Het
Csf2ra	C	A	19: 61,226,344	D181Y	probably damaging	Het
Csmd1	T	A	8: 15,932,610	I2686F	probably damaging	Het
Dhx29	T	C	13: 112,945,086	S415P	probably benign	Het
Dsel	A	T	1: 111,860,915	F630Y	probably damaging	Het
Ell	T	A	8: 70,578,940	I96N	possibly damaging	Het
Ephx2	T	A	14: 66,088,303	I358L	probably benign	Het
Fam162b	A	G	10: 51,587,211	I120T	probably damaging	Het
Fam187a	T	C	11: 102,885,780	Y137H	probably damaging	Het
Fastk	T	C	5: 24,441,803	E403G	probably damaging	Het
Fcrlb	C	A	1: 170,907,332	V409F	probably benign	Het
Flot2	G	T	11: 78,058,005	A269S	probably benign	Het
Gpd2	T	A	2: 57,355,551	N419K	probably damaging	Het
Hecw1	A	T	13: 14,377,765	M61K	probably null	Het
Htr2a	T	C	14: 74,706,128	F383L	probably damaging	Het
Kctd6	C	T	14: 8,222,253	R32C	probably damaging	Het
Khdc1a	A	G	1: 21,350,965	T125A	probably benign	Het
Klhl40	T	C	9: 121,779,938	S390P	probably benign	Het
Lonp1	G	A	17: 56,614,956	T808I	probably damaging	Het
Loxhd1	A	C	18: 77,404,889	D1342A	probably damaging	Het
Lrat	T	C	3: 82,897,110	I187V	probably benign	Het
Lrif1	T	C	3: 106,735,846	*238Q	probably null	Het
Lrp2bp	T	C	8: 46,011,988	F48S	probably benign	Het
Mafg	A	G	11: 120,629,678	M32T	possibly damaging	Het
Map4	C	T	9: 110,034,955	T416I	probably benign	Het
N4bp2	T	C	5: 65,808,316	F1236S	probably damaging	Het
Nfatc3	A	G	8: 106,083,834	D414G	probably damaging	Het
Nrip2	T	G	6: 128,405,074	V50G	probably damaging	Het
Olfr1449	T	A	19: 12,934,843	I35N	probably damaging	Het
Olfr16	A	G	1: 172,956,807	N4S	probably benign	Het
Olfr432	A	T	1: 174,050,799	K142I	probably benign	Het
Olfr608	T	A	7: 103,470,146	F36I	possibly damaging	Het
Pcdhb18	A	T	18: 37,490,769	H384L	probably benign	Het
Pik3r1	A	T	13: 101,686,374	Y607N	probably damaging	Het
Plagl2	G	A	2: 153,232,477	T168I	probably damaging	Het
Polr2a	A	G	11: 69,742,396	S912P	probably damaging	Het
Ppp1r16b	A	G	2: 158,761,495	K447E	possibly damaging	Het
Prkd1	T	C	12: 50,342,039	E907G	possibly damaging	Het
Rabep2	A	G	7: 126,444,540	R470G	probably damaging	Het
Rasal2	T	C	1: 157,174,160	Y518C	probably damaging	Het
Rbmxl1	A	G	8: 78,506,082	Y211H	probably damaging	Het
Rdh7	T	C	10: 127,884,585	Y306C	probably benign	Het
Rtn3	T	C	19: 7,457,911	I220V	probably damaging	Het
Scube1	T	C	15: 83,607,437	H952R	probably damaging	Het
Sf3b1	A	G	1: 55,000,652	I690T	probably damaging	Het
Sharpin	T	C	15: 76,347,936	K240R	probably benign	Het
Skint5	A	G	4: 113,563,459	I1108T	unknown	Het
Snip1	A	G	4: 125,071,201	D133G	probably benign	Het
St3gal3	T	C	4: 118,014,774	Y77C	probably damaging	Het
Sytl3	T	C	17: 6,715,481	V112A	probably benign	Het
Tnxb	C	T	17: 34,717,970	P3718S	probably damaging	Het
Ttc24	A	T	3: 88,073,094		probably null	Het
Ubr3	A	T	2: 70,009,129	E1529V	probably damaging	Het
Utrn	T	A	10: 12,710,138	H965L	probably benign	Het
Xrn2	T	A	2: 147,061,423	L781Q	probably damaging	Het
Zbtb11	T	C	16: 55,990,682	I401T	probably benign	Het
Zc3h14	C	T	12: 98,758,580	P167L	probably damaging	Het
Zfp609	G	T	9: 65,703,092	S863*	probably null	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
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
R4631:Scn8a	UTSW	15	101016503	nonsense	probably null
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
R8983:Scn8a	UTSW	15	101002149	missense	possibly damaging	0.81
R9034:Scn8a	UTSW	15	101029761	missense	probably damaging	0.98
R9050:Scn8a	UTSW	15	101008280	missense	possibly damaging	0.80
R9240:Scn8a	UTSW	15	101017187	nonsense	probably null
R9249:Scn8a	UTSW	15	101016575	missense	probably benign	0.00
R9462:Scn8a	UTSW	15	101032278	missense
R9599:Scn8a	UTSW	15	101013291	missense	probably damaging	1.00
R9609:Scn8a	UTSW	15	100936526	missense	possibly damaging	0.91
R9653:Scn8a	UTSW	15	101040066	missense	probably damaging	1.00
R9794:Scn8a	UTSW	15	101035451	missense	probably benign	0.00
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'- GTGCTGAACTTATTTCTGGCCTTGC -3'
(R):5'- GACTCGCTGCTAACATCCTCTGTG -3'

Sequencing Primer
(F):5'- AGCGCAGACAATCTGGC -3'
(R):5'- GGTTCTCGAAATCAGACTCGC -3'

Posted On

2014-05-23