Mutagenetix > Incidental Mutation

Incidental Mutation 'R6677:Scn8a'

527326

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

044796-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.790) question?

Stock #

R6677 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

100767739-100943819 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 100866953 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 103 (D103G)

Ref Sequence

ENSEMBL: ENSMUSP00000143876 (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 damaging
Transcript: ENSMUST00000082209
AA Change: D253G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000080842
Gene: ENSMUSG00000023033
AA Change: D253G

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: D253G

PolyPhen 2 Score 0.628 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000104536
Gene: ENSMUSG00000023033
AA Change: D253G

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: D253G

PolyPhen 2 Score 0.215 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000104537
Gene: ENSMUSG00000023033
AA Change: D253G

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: D253G

PolyPhen 2 Score 0.628 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000104538
Gene: ENSMUSG00000023033
AA Change: D253G

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: D253G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000144371
Gene: ENSMUSG00000023033
AA Change: D253G

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

probably damaging
Transcript: ENSMUST00000201518
AA Change: D253G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000143879
Gene: ENSMUSG00000023033
AA Change: D253G

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 damaging
Transcript: ENSMUST00000201549
AA Change: D253G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000144013
Gene: ENSMUSG00000023033
AA Change: D253G

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 damaging
Transcript: ENSMUST00000202702
AA Change: D103G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000143876
Gene: ENSMUSG00000023033
AA Change: D103G

Domain	Start	End	E-Value	Type
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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000202971

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000202452

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.4%
20x: 95.7%

Validation Efficiency

100% (31/31)

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: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc12	G	T	8: 87,261,381 (GRCm39)	H713Q	possibly damaging	Het
Akap9	A	G	5: 4,079,869 (GRCm39)	T1874A	probably benign	Het
Atl1	A	G	12: 70,000,218 (GRCm39)	I289M	probably damaging	Het
Atp12a	A	G	14: 56,618,311 (GRCm39)	D654G	probably damaging	Het
Bbox1	C	A	2: 110,135,770 (GRCm39)	D70Y	probably damaging	Het
Blzf1	A	T	1: 164,130,181 (GRCm39)	V50D	possibly damaging	Het
Ccdc168	G	T	1: 44,097,859 (GRCm39)	R1080S	probably benign	Het
Cfap65	C	A	1: 74,943,844 (GRCm39)	D1556Y	probably damaging	Het
Chrm2	A	T	6: 36,501,027 (GRCm39)	N295Y	probably damaging	Het
Clca3b	T	A	3: 144,529,145 (GRCm39)	E843V	probably benign	Het
Enpp3	T	A	10: 24,653,855 (GRCm39)	N701Y	possibly damaging	Het
Fbxo30	G	T	10: 11,166,380 (GRCm39)	L367F	possibly damaging	Het
Gm4841	A	T	18: 60,403,652 (GRCm39)	F147Y	probably damaging	Het
Itprid2	A	G	2: 79,485,445 (GRCm39)	T500A	possibly damaging	Het
Lama1	G	A	17: 68,102,228 (GRCm39)	V1951I	probably benign	Het
Mgat4b	A	G	11: 50,123,898 (GRCm39)		probably null	Het
Mpp3	A	G	11: 101,899,444 (GRCm39)	V359A	probably benign	Het
Nhsl1	T	A	10: 18,401,610 (GRCm39)	D911E	probably damaging	Het
Or13a23-ps1	T	G	7: 140,118,465 (GRCm39)	F12V	probably damaging	Het
Polr1b	T	C	2: 128,962,131 (GRCm39)		probably benign	Het
Qrfprl	A	T	6: 65,433,229 (GRCm39)	I350F	probably benign	Het
Rnd2	C	T	11: 101,359,825 (GRCm39)	L57F	probably damaging	Het
Saxo2	T	C	7: 82,284,484 (GRCm39)	R125G	probably benign	Het
Sfxn2	A	T	19: 46,570,967 (GRCm39)	N9I	possibly damaging	Het
Shroom1	G	A	11: 53,354,343 (GRCm39)	A88T	possibly damaging	Het
Slc24a5	G	T	2: 124,922,615 (GRCm39)	A126S	possibly damaging	Het
Sult5a1	A	G	8: 123,876,017 (GRCm39)	F100L	probably benign	Het
Syne1	T	C	10: 4,990,942 (GRCm39)	Q579R	possibly damaging	Het
Vmn1r113	G	A	7: 20,521,903 (GRCm39)	G232S	probably benign	Het
Zic5	C	G	14: 122,702,566 (GRCm39)	R55P	unknown	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
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
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'- CCGTATTTCAAGTGGTGGTCC -3'
(R):5'- TTCCAAGCTCCATCTGGCTG -3'

Sequencing Primer
(F):5'- TCCTCTGGGGAGAGTAGAGC -3'
(R):5'- CTGGGCCGGACCACTTTTTG -3'

Posted On

2018-07-23