Mutagenetix > Incidental Mutation

Incidental Mutation 'R0945:Scn8a'

82075

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

039084-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.790) question?

Stock #

R0945 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

100767739-100943819 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 100913668 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 1020 (H1020R)

Ref Sequence

ENSEMBL: ENSMUSP00000144013 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000082209
AA Change: H1020R

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000080842
Gene: ENSMUSG00000023033
AA Change: H1020R

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: H1020R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000104536
Gene: ENSMUSG00000023033
AA Change: H1020R

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: H1030R

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000104537
Gene: ENSMUSG00000023033
AA Change: H1030R

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: H1020R

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000104538
Gene: ENSMUSG00000023033
AA Change: H1020R

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 benign
Transcript: ENSMUST00000200963
AA Change: H1020R

PolyPhen 2 Score 0.386 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000144371
Gene: ENSMUSG00000023033
AA Change: H1020R

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

possibly damaging
Transcript: ENSMUST00000201549
AA Change: H1020R

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000144013
Gene: ENSMUSG00000023033
AA Change: H1020R

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

0.0757

Coding Region Coverage

1x: 99.5%
3x: 99.1%
10x: 98.1%
20x: 96.8%

Validation Efficiency

98% (44/45)

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: 43 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy5	A	G	16: 35,110,481 (GRCm39)	M883V	probably benign	Het
Allc	A	G	12: 28,609,962 (GRCm39)	S212P	probably benign	Het
Anxa10	A	G	8: 62,513,279 (GRCm39)		probably benign	Het
Apoa2	A	G	1: 171,053,268 (GRCm39)		probably null	Het
Arfgef2	T	C	2: 166,668,889 (GRCm39)		probably benign	Het
Arhgap30	G	T	1: 171,230,854 (GRCm39)	V204L	probably damaging	Het
Cd109	T	A	9: 78,596,223 (GRCm39)	V852E	possibly damaging	Het
Ceacam5	T	A	7: 17,481,269 (GRCm39)	Y339N	probably damaging	Het
Chaf1a	A	G	17: 56,374,441 (GRCm39)	D876G	probably damaging	Het
Chd9	A	G	8: 91,659,630 (GRCm39)	K197E	possibly damaging	Het
Cnr2	A	T	4: 135,644,632 (GRCm39)	M237L	probably benign	Het
Dnm2	C	A	9: 21,416,956 (GRCm39)	Q830K	probably damaging	Het
Dst	T	C	1: 34,310,500 (GRCm39)	L1615P	probably damaging	Het
Eid1	A	G	2: 125,515,497 (GRCm39)	D129G	probably damaging	Het
Exoc5	A	G	14: 49,276,799 (GRCm39)		probably benign	Het
Greb1	T	C	12: 16,723,803 (GRCm39)	Y1854C	probably benign	Het
Il15ra	T	A	2: 11,723,138 (GRCm39)	V54E	probably damaging	Het
Il4i1	G	A	7: 44,489,128 (GRCm39)	V306M	probably damaging	Het
Lrsam1	T	C	2: 32,837,921 (GRCm39)	D211G	probably benign	Het
Miga1	A	T	3: 152,023,300 (GRCm39)	F250L	possibly damaging	Het
Myrfl	C	T	10: 116,639,299 (GRCm39)		probably benign	Het
Nell1	A	G	7: 49,869,333 (GRCm39)	I203V	probably benign	Het
Ofcc1	C	T	13: 40,362,305 (GRCm39)	G206R	probably benign	Het
Or14j9	G	A	17: 37,874,278 (GRCm39)	T308I	probably benign	Het
Or4a15	T	C	2: 89,193,599 (GRCm39)	Y58C	probably damaging	Het
Or52u1	T	A	7: 104,237,879 (GRCm39)	N289K	probably damaging	Het
Pdxdc1	A	G	16: 13,675,296 (GRCm39)	L345P	probably damaging	Het
Pex3	C	A	10: 13,418,420 (GRCm39)	A79S	probably benign	Het
Pla2r1	A	C	2: 60,288,754 (GRCm39)	L626R	possibly damaging	Het
Plcb3	A	G	19: 6,932,246 (GRCm39)	S1107P	probably damaging	Het
Ppcdc	C	T	9: 57,327,441 (GRCm39)		probably null	Het
Rbak	A	T	5: 143,159,334 (GRCm39)	F573Y	probably damaging	Het
Rfc1	A	G	5: 65,436,052 (GRCm39)		probably null	Het
Rpl13	C	T	8: 123,831,913 (GRCm39)	A203V	possibly damaging	Het
Slf1	A	G	13: 77,251,590 (GRCm39)		probably benign	Het
Synj1	A	G	16: 90,757,333 (GRCm39)	L905S	possibly damaging	Het
Tmem59	T	A	4: 107,044,922 (GRCm39)		probably benign	Het
Ugcg	C	T	4: 59,207,798 (GRCm39)	P46S	probably benign	Het
Uri1	A	T	7: 37,669,103 (GRCm39)	D127E	probably damaging	Het
Usp31	T	C	7: 121,269,476 (GRCm39)	E489G	probably damaging	Het
Zfp329	T	A	7: 12,545,395 (GRCm39)	N43I	probably benign	Het
Zfp941	C	T	7: 140,391,577 (GRCm39)	R594H	probably damaging	Het
Zfy1	T	C	Y: 725,983 (GRCm39)	D594G	probably damaging	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
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
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'- GTGCTGAACTTATTTCTGGCCTTGC -3'
(R):5'- GACTCGCTGCTAACATCCTCTGTG -3'

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

Posted On

2013-11-08