Mutagenetix > Incidental Mutation

Incidental Mutation 'R5464:Scn2a'

433136

Institutional Source

Beutler Lab

Gene Symbol

Scn2a

Ensembl Gene

ENSMUSG00000075318

Gene Name

sodium channel, voltage-gated, type II, alpha

Synonyms

A230052E19Rik, Nav1.2, Scn2a1

MMRRC Submission

042850-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5464 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

65451115-65597791 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 65532100 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Cysteine at position 571 (R571C)

Ref Sequence

ENSEMBL: ENSMUSP00000143882 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028377] [ENSMUST00000100067] [ENSMUST00000200829]

AlphaFold

B1AWN6

Predicted Effect

probably damaging
Transcript: ENSMUST00000028377
AA Change: R571C

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

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: R571C

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	2.2e-81	PFAM
low complexity region	450	471	N/A	INTRINSIC
Pfam:Na_trans_cytopl	505	710	9.6e-83	PFAM
Pfam:Ion_trans	759	994	3.6e-57	PFAM
Pfam:Na_trans_assoc	998	1204	1.7e-63	PFAM
Pfam:Ion_trans	1208	1484	3.3e-66	PFAM
Pfam:Ion_trans	1531	1788	2.8e-57	PFAM
Pfam:PKD_channel	1627	1782	8.6e-7	PFAM
IQ	1905	1927	3.59e-3	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000100067
AA Change: R571C

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

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: R571C

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	157	424	3.3e-75	PFAM
low complexity region	433	448	N/A	INTRINSIC
low complexity region	450	471	N/A	INTRINSIC
Pfam:DUF3451	488	711	2.6e-66	PFAM
Pfam:Ion_trans	794	983	1.1e-47	PFAM
Pfam:Na_trans_assoc	998	1219	3.5e-77	PFAM
Pfam:Ion_trans	1245	1473	4.4e-55	PFAM
PDB:1BYY\|A	1475	1527	3e-31	PDB
Pfam:Ion_trans	1566	1776	2.4e-52	PFAM
Pfam:PKD_channel	1628	1783	3.6e-7	PFAM
IQ	1905	1927	3.59e-3	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000200829
AA Change: R571C

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

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: R571C

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	1.2e-79	PFAM
low complexity region	450	471	N/A	INTRINSIC
Pfam:Na_trans_cytopl	505	710	7.1e-80	PFAM
Pfam:Ion_trans	759	994	2.1e-55	PFAM
Pfam:Na_trans_assoc	998	1204	8e-61	PFAM
Pfam:Ion_trans	1208	1484	1.9e-64	PFAM
Pfam:Ion_trans	1531	1788	1.6e-55	PFAM
Pfam:PKD_channel	1627	1782	1.2e-4	PFAM
IQ	1905	1927	1.8e-5	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.2%
20x: 95.2%

Validation Efficiency

MGI Phenotype

FUNCTION: Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. In humans, variants of this gene are associated with seizure disorders and autism spectrum disorder. Mice homozygous for a knockout mutation die with severe hypoxia and extensive neuronal cell death, while gain of function mutations result in progressive seizure disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
PHENOTYPE: Homozygotes for a targeted mutation exhibit excess neuronal apoptosis (especially in the brainstem), reduced neuronal sodium channel currents in vitro, and severe hypoxia resulting in neonatal lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 49 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930562C15Rik	G	A	16: 4,682,227 (GRCm39)	G180E	probably damaging	Het
Acsl1	T	A	8: 46,958,775 (GRCm39)	D95E	probably benign	Het
Acyp2	C	T	11: 30,456,354 (GRCm39)	E98K	possibly damaging	Het
Adamts16	T	A	13: 70,909,868 (GRCm39)	H895L	probably benign	Het
Alox12e	T	C	11: 70,208,505 (GRCm39)	Y483C	probably damaging	Het
Atp13a2	T	A	4: 140,733,381 (GRCm39)	F952I	probably damaging	Het
Crot	T	G	5: 9,033,690 (GRCm39)		probably null	Het
Dnaja1	T	A	4: 40,724,133 (GRCm39)	M98K	probably benign	Het
Eps8	C	T	6: 137,504,473 (GRCm39)	G87R	probably damaging	Het
Flg2	C	A	3: 93,109,277 (GRCm39)	T435K	possibly damaging	Het
Gpatch4	T	C	3: 87,962,062 (GRCm39)		probably null	Het
Heatr1	T	A	13: 12,448,524 (GRCm39)	M1795K	probably benign	Het
Ift52	T	C	2: 162,871,735 (GRCm39)	V189A	probably benign	Het
Kif21a	T	A	15: 90,878,058 (GRCm39)	D250V	probably damaging	Het
Lrrc66	T	C	5: 73,765,622 (GRCm39)	T474A	probably benign	Het
Mcub	T	C	3: 129,709,365 (GRCm39)	E316G	probably benign	Het
Mettl15	C	T	2: 109,021,967 (GRCm39)	V113I	probably benign	Het
Mroh8	T	A	2: 157,063,150 (GRCm39)	I824F	probably damaging	Het
Mrpl19	A	G	6: 81,938,992 (GRCm39)	M270T	probably damaging	Het
Naa12	C	T	18: 80,255,138 (GRCm39)	A144V	probably damaging	Het
Or10d4	A	T	9: 39,581,066 (GRCm39)	T238S	probably damaging	Het
Or4ac1-ps1	T	C	2: 88,370,599 (GRCm39)	Y58C	probably null	Het
Or51a25	A	G	7: 102,373,124 (GRCm39)	V191A	possibly damaging	Het
Or51a39	T	C	7: 102,362,889 (GRCm39)	T244A	probably benign	Het
Or51a43	C	A	7: 103,717,674 (GRCm39)	R188L	possibly damaging	Het
Or51f5	A	G	7: 102,424,640 (GRCm39)	K303R	probably benign	Het
Or52a24	T	A	7: 103,381,396 (GRCm39)	W88R	probably damaging	Het
Or5ak23	AAGTCTGGAGTC	AAGTC	2: 85,245,057 (GRCm39)		probably null	Het
Or6x1	T	C	9: 40,099,080 (GRCm39)	I223T	probably damaging	Het
Pacs1	T	C	19: 5,197,235 (GRCm39)	M430V	probably benign	Het
Piezo2	A	G	18: 63,278,176 (GRCm39)	S243P	probably damaging	Het
Ppp1r36	A	T	12: 76,474,852 (GRCm39)		probably null	Het
Prdm16	T	A	4: 154,430,601 (GRCm39)		probably null	Het
Prss36	A	T	7: 127,533,405 (GRCm39)	W97R	probably damaging	Het
Psmg4	A	T	13: 34,362,047 (GRCm39)	I112F	probably damaging	Het
Ptpru	C	T	4: 131,499,868 (GRCm39)	G1259R	probably damaging	Het
Rsph4a	T	C	10: 33,785,337 (GRCm39)	I416T	possibly damaging	Het
Selenbp1	A	G	3: 94,851,727 (GRCm39)	M423V	probably benign	Het
Serpina3i	G	A	12: 104,234,751 (GRCm39)	A361T	possibly damaging	Het
Serpinb3c	A	T	1: 107,199,434 (GRCm39)	D362E	probably damaging	Het
Sf3a3	T	C	4: 124,622,033 (GRCm39)		probably null	Het
Sgcg	A	G	14: 61,474,304 (GRCm39)	V113A	possibly damaging	Het
Slc3a2	T	C	19: 8,691,008 (GRCm39)	K74R	probably damaging	Het
Smco1	T	A	16: 32,092,694 (GRCm39)	W122R	probably damaging	Het
Snx19	A	G	9: 30,339,269 (GRCm39)	K136E	possibly damaging	Het
Trim32	A	G	4: 65,532,625 (GRCm39)	N394S	probably damaging	Het
Uqcrb	T	C	13: 67,048,889 (GRCm39)	D87G	probably damaging	Het
Wipf3	T	C	6: 54,462,308 (GRCm39)	S173P	possibly damaging	Het
Zfp473	T	C	7: 44,382,062 (GRCm39)	E756G	probably damaging	Het

Other mutations in Scn2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00088:Scn2a	APN	2	65,594,784 (GRCm39)	missense	probably benign
IGL00159:Scn2a	APN	2	65,573,434 (GRCm39)	missense	probably damaging	1.00
IGL00418:Scn2a	APN	2	65,594,866 (GRCm39)	missense	probably benign	0.43
IGL00753:Scn2a	APN	2	65,514,207 (GRCm39)	missense	possibly damaging	0.66
IGL00770:Scn2a	APN	2	65,566,197 (GRCm39)	missense	probably damaging	1.00
IGL00774:Scn2a	APN	2	65,566,197 (GRCm39)	missense	probably damaging	1.00
IGL00847:Scn2a	APN	2	65,501,078 (GRCm39)	missense	probably damaging	1.00
IGL01155:Scn2a	APN	2	65,548,092 (GRCm39)	missense	probably damaging	1.00
IGL01329:Scn2a	APN	2	65,547,852 (GRCm39)	missense	probably benign	0.05
IGL01537:Scn2a	APN	2	65,546,219 (GRCm39)	missense	probably benign	0.00
IGL01672:Scn2a	APN	2	65,582,278 (GRCm39)	missense	probably damaging	1.00
IGL01958:Scn2a	APN	2	65,532,173 (GRCm39)	missense	probably damaging	1.00
IGL02028:Scn2a	APN	2	65,594,002 (GRCm39)	missense	probably damaging	0.96
IGL02142:Scn2a	APN	2	65,546,182 (GRCm39)	missense	probably damaging	1.00
IGL02160:Scn2a	APN	2	65,560,460 (GRCm39)	missense	probably damaging	1.00
IGL02183:Scn2a	APN	2	65,501,947 (GRCm39)	missense	probably benign	0.20
IGL02341:Scn2a	APN	2	65,518,721 (GRCm39)	missense	probably damaging	1.00
IGL02504:Scn2a	APN	2	65,514,228 (GRCm39)	missense	probably benign	0.02
IGL02530:Scn2a	APN	2	65,560,522 (GRCm39)	missense	probably damaging	0.99
IGL02621:Scn2a	APN	2	65,579,223 (GRCm39)	splice site	probably benign
IGL02652:Scn2a	APN	2	65,532,382 (GRCm39)	missense	possibly damaging	0.82
IGL02966:Scn2a	APN	2	65,532,188 (GRCm39)	missense	possibly damaging	0.93
IGL03188:Scn2a	APN	2	65,501,997 (GRCm39)	missense	probably damaging	0.99
IGL03329:Scn2a	APN	2	65,594,973 (GRCm39)	missense	probably benign
IGL03336:Scn2a	APN	2	65,519,088 (GRCm39)	missense	probably damaging	1.00
IGL03391:Scn2a	APN	2	65,594,557 (GRCm39)	missense	probably damaging	1.00
PIT4280001:Scn2a	UTSW	2	65,546,074 (GRCm39)	missense	probably damaging	1.00
PIT4362001:Scn2a	UTSW	2	65,514,182 (GRCm39)	missense	probably benign	0.09
PIT4403001:Scn2a	UTSW	2	65,542,252 (GRCm39)	missense	probably damaging	1.00
PIT4520001:Scn2a	UTSW	2	65,518,763 (GRCm39)	missense	probably damaging	1.00
R0021:Scn2a	UTSW	2	65,500,859 (GRCm39)	missense	possibly damaging	0.51
R0141:Scn2a	UTSW	2	65,542,160 (GRCm39)	missense	probably benign	0.01
R0240:Scn2a	UTSW	2	65,566,118 (GRCm39)	missense	probably benign	0.32
R0240:Scn2a	UTSW	2	65,566,118 (GRCm39)	missense	probably benign	0.32
R0335:Scn2a	UTSW	2	65,512,435 (GRCm39)	missense	probably damaging	1.00
R0508:Scn2a	UTSW	2	65,548,186 (GRCm39)	missense	probably damaging	0.99
R0558:Scn2a	UTSW	2	65,542,269 (GRCm39)	missense	probably benign	0.26
R0600:Scn2a	UTSW	2	65,532,177 (GRCm39)	missense	possibly damaging	0.90
R0667:Scn2a	UTSW	2	65,582,340 (GRCm39)	missense	possibly damaging	0.91
R1178:Scn2a	UTSW	2	65,517,123 (GRCm39)	splice site	probably benign
R1244:Scn2a	UTSW	2	65,593,999 (GRCm39)	missense	probably damaging	0.98
R1386:Scn2a	UTSW	2	65,519,085 (GRCm39)	missense	probably damaging	1.00
R1434:Scn2a	UTSW	2	65,532,335 (GRCm39)	missense	possibly damaging	0.79
R1440:Scn2a	UTSW	2	65,594,938 (GRCm39)	missense	probably benign
R1448:Scn2a	UTSW	2	65,514,189 (GRCm39)	missense	probably benign	0.17
R1460:Scn2a	UTSW	2	65,532,187 (GRCm39)	missense	probably damaging	0.96
R1553:Scn2a	UTSW	2	65,544,180 (GRCm39)	nonsense	probably null
R1642:Scn2a	UTSW	2	65,514,041 (GRCm39)	missense	probably damaging	1.00
R1803:Scn2a	UTSW	2	65,501,111 (GRCm39)	splice site	probably null
R1981:Scn2a	UTSW	2	65,520,514 (GRCm39)	missense	probably damaging	1.00
R2002:Scn2a	UTSW	2	65,512,427 (GRCm39)	missense	probably null	1.00
R2068:Scn2a	UTSW	2	65,582,417 (GRCm39)	missense	probably benign	0.14
R2125:Scn2a	UTSW	2	65,582,423 (GRCm39)	nonsense	probably null
R2126:Scn2a	UTSW	2	65,582,423 (GRCm39)	nonsense	probably null
R2876:Scn2a	UTSW	2	65,546,241 (GRCm39)	missense	possibly damaging	0.64
R2878:Scn2a	UTSW	2	65,518,715 (GRCm39)	missense	probably damaging	1.00
R3113:Scn2a	UTSW	2	65,579,129 (GRCm39)	missense	possibly damaging	0.86
R3749:Scn2a	UTSW	2	65,544,115 (GRCm39)	missense	probably damaging	1.00
R3750:Scn2a	UTSW	2	65,544,115 (GRCm39)	missense	probably damaging	1.00
R3765:Scn2a	UTSW	2	65,513,054 (GRCm39)	missense	possibly damaging	0.51
R3850:Scn2a	UTSW	2	65,512,375 (GRCm39)	missense	probably benign	0.14
R4585:Scn2a	UTSW	2	65,573,395 (GRCm39)	splice site	probably null
R4586:Scn2a	UTSW	2	65,573,395 (GRCm39)	splice site	probably null
R4588:Scn2a	UTSW	2	65,544,111 (GRCm39)	missense	possibly damaging	0.76
R4622:Scn2a	UTSW	2	65,582,371 (GRCm39)	missense	probably benign	0.04
R5108:Scn2a	UTSW	2	65,518,974 (GRCm39)	missense	probably damaging	1.00
R5161:Scn2a	UTSW	2	65,594,935 (GRCm39)	missense	probably benign	0.00
R5235:Scn2a	UTSW	2	65,582,355 (GRCm39)	missense	probably damaging	1.00
R5586:Scn2a	UTSW	2	65,537,639 (GRCm39)	nonsense	probably null
R5630:Scn2a	UTSW	2	65,556,709 (GRCm39)	missense	probably damaging	1.00
R5715:Scn2a	UTSW	2	65,547,928 (GRCm39)	missense	probably benign	0.27
R5730:Scn2a	UTSW	2	65,512,882 (GRCm39)	nonsense	probably null
R5734:Scn2a	UTSW	2	65,548,066 (GRCm39)	missense	possibly damaging	0.49
R5779:Scn2a	UTSW	2	65,594,827 (GRCm39)	missense	probably benign	0.00
R6133:Scn2a	UTSW	2	65,573,448 (GRCm39)	missense	probably benign	0.35
R6547:Scn2a	UTSW	2	65,546,241 (GRCm39)	missense	probably benign	0.29
R6549:Scn2a	UTSW	2	65,595,018 (GRCm39)	missense	probably benign	0.05
R6818:Scn2a	UTSW	2	65,519,013 (GRCm39)	nonsense	probably null
R6999:Scn2a	UTSW	2	65,512,453 (GRCm39)	missense	probably benign
R7069:Scn2a	UTSW	2	65,594,950 (GRCm39)	missense	probably benign	0.00
R7073:Scn2a	UTSW	2	65,558,787 (GRCm39)	missense	probably benign	0.00
R7125:Scn2a	UTSW	2	65,594,277 (GRCm39)	missense	probably damaging	1.00
R7178:Scn2a	UTSW	2	65,579,197 (GRCm39)	nonsense	probably null
R7179:Scn2a	UTSW	2	65,532,323 (GRCm39)	missense	probably damaging	1.00
R7203:Scn2a	UTSW	2	65,578,663 (GRCm39)	missense	probably benign	0.01
R7227:Scn2a	UTSW	2	65,582,367 (GRCm39)	missense	probably damaging	0.98
R7269:Scn2a	UTSW	2	65,594,113 (GRCm39)	missense	probably damaging	1.00
R7358:Scn2a	UTSW	2	65,512,850 (GRCm39)	nonsense	probably null
R7388:Scn2a	UTSW	2	65,518,998 (GRCm39)	missense	probably damaging	1.00
R7491:Scn2a	UTSW	2	65,532,352 (GRCm39)	missense	probably damaging	0.99
R7619:Scn2a	UTSW	2	65,546,247 (GRCm39)	missense	probably damaging	1.00
R7695:Scn2a	UTSW	2	65,542,251 (GRCm39)	missense	probably damaging	0.99
R7735:Scn2a	UTSW	2	65,594,013 (GRCm39)	missense	probably benign	0.40
R7911:Scn2a	UTSW	2	65,512,427 (GRCm39)	missense	probably null	1.00
R8096:Scn2a	UTSW	2	65,594,366 (GRCm39)	missense	probably damaging	0.98
R8172:Scn2a	UTSW	2	65,520,672 (GRCm39)	missense	probably benign	0.01
R8220:Scn2a	UTSW	2	65,520,620 (GRCm39)	missense	probably benign	0.01
R8333:Scn2a	UTSW	2	65,514,191 (GRCm39)	missense	probably benign	0.01
R8416:Scn2a	UTSW	2	65,511,345 (GRCm39)	missense	probably benign	0.00
R8850:Scn2a	UTSW	2	65,518,730 (GRCm39)	missense	probably damaging	1.00
R8897:Scn2a	UTSW	2	65,546,002 (GRCm39)	critical splice acceptor site	probably null
R8977:Scn2a	UTSW	2	65,594,014 (GRCm39)	missense	probably damaging	0.99
R8992:Scn2a	UTSW	2	65,594,242 (GRCm39)	missense	probably damaging	1.00
R9190:Scn2a	UTSW	2	65,511,346 (GRCm39)	missense	probably benign	0.00
R9206:Scn2a	UTSW	2	65,548,131 (GRCm39)	missense	probably damaging	1.00
R9355:Scn2a	UTSW	2	65,594,433 (GRCm39)	missense	probably damaging	1.00
R9452:Scn2a	UTSW	2	65,595,163 (GRCm39)	missense	probably benign
R9529:Scn2a	UTSW	2	65,594,932 (GRCm39)	missense	probably damaging	0.99
R9567:Scn2a	UTSW	2	65,518,974 (GRCm39)	missense	probably damaging	1.00
R9569:Scn2a	UTSW	2	65,560,622 (GRCm39)	missense	probably damaging	1.00
R9657:Scn2a	UTSW	2	65,566,032 (GRCm39)	missense	probably damaging	1.00
R9715:Scn2a	UTSW	2	65,579,149 (GRCm39)	missense	possibly damaging	0.93
R9761:Scn2a	UTSW	2	65,566,030 (GRCm39)	missense	probably damaging	1.00
Z1176:Scn2a	UTSW	2	65,582,212 (GRCm39)	missense	possibly damaging	0.84
Z1177:Scn2a	UTSW	2	65,548,079 (GRCm39)	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- AGACAGCATTGTGGGAGTGC -3'
(R):5'- TCATGGGTAGAGTGGGTATCCC -3'

Sequencing Primer
(F):5'- GAGTGCTTTTGACTACTCTTAAGC -3'
(R):5'- GTCGTTGTCCTCAAACGT -3'

Posted On

2016-10-06