Mutagenetix > Incidental Mutations

Incidental Mutation 'R2002:Scn2a'

223142

Institutional Source

Beutler Lab

Gene Symbol

Scn2a

Ensembl Gene

ENSMUSG00000075318

Gene Name

sodium channel, voltage-gated, type II, alpha

Synonyms

A230052E19Rik, Scn2a1, Nav1.2

MMRRC Submission

040012-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R2002 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

65620771-65767447 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 65682083 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Glutamine at position 188 (R188Q)

Ref Sequence

ENSEMBL: ENSMUSP00000143882 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028377] [ENSMUST00000100067] [ENSMUST00000144254] [ENSMUST00000200829]

AlphaFold

B1AWN6

Predicted Effect

probably null
Transcript: ENSMUST00000028377
AA Change: R188Q

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: R188Q

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 null
Transcript: ENSMUST00000100067
AA Change: R188Q

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: R188Q

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

noncoding transcript
Transcript: ENSMUST00000138368

Predicted Effect

probably null
Transcript: ENSMUST00000144254
AA Change: R188Q

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000117955
Gene: ENSMUSG00000075318
AA Change: R188Q

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	7.2e-81	PFAM
low complexity region	450	471	N/A	INTRINSIC
low complexity region	484	502	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000200829
AA Change: R188Q

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: R188Q

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

Meta Mutation Damage Score

0.9032

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.2%
20x: 91.6%

Validation Efficiency

97% (72/74)

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930548G14Rik	T	C	15: 46,625,606		noncoding transcript	Het
Abcb4	T	A	5: 8,905,989	S98T	probably benign	Het
Acan	T	C	7: 79,100,793	S1771P	probably damaging	Het
Acvr1c	T	A	2: 58,315,975	Q41L	probably benign	Het
Ak2	T	A	4: 129,008,229	S232T	probably benign	Het
Akr1e1	T	A	13: 4,607,565		probably benign	Het
Ano7	T	C	1: 93,400,581		probably benign	Het
Aox1	T	A	1: 58,047,141	H68Q	possibly damaging	Het
Apaf1	A	G	10: 91,061,814	V269A	possibly damaging	Het
Apba2	A	T	7: 64,733,542	I368F	probably damaging	Het
Armc3	A	G	2: 19,288,936	M513V	probably benign	Het
Asb5	G	A	8: 54,583,620	V116M	probably damaging	Het
Atg16l2	A	G	7: 101,294,920	S280P	possibly damaging	Het
Atp6v0c	G	T	17: 24,164,861	T40K	probably damaging	Het
C330027C09Rik	T	C	16: 49,005,851		probably benign	Het
Cdk2ap2	A	G	19: 4,097,903	M57V	possibly damaging	Het
Ctnnd1	T	C	2: 84,620,360	N172S	probably benign	Het
Ddx55	T	A	5: 124,566,440	V370E	probably damaging	Het
Ddx6	A	G	9: 44,607,534	T48A	probably benign	Het
Dnah10	C	T	5: 124,833,988	R4490W	probably damaging	Het
Dspp	T	A	5: 104,178,559	S929R	unknown	Het
Erbb3	T	C	10: 128,586,225	Y50C	probably benign	Het
Fam209	C	A	2: 172,472,769	N59K	probably benign	Het
Fgd3	T	C	13: 49,296,455	E106G	probably benign	Het
Frmd4a	A	C	2: 4,572,365	K344T	probably damaging	Het
Gbe1	A	G	16: 70,528,926	E617G	probably damaging	Het
Gm5089	T	A	14: 122,436,274	I12F	unknown	Het
Gm7052	T	A	17: 22,039,939		probably benign	Het
Gria1	A	T	11: 57,012,104	N24I	possibly damaging	Het
Grin2b	T	C	6: 135,733,245	E1101G	probably damaging	Het
Hjurp	GT	GTT	1: 88,266,524		probably null	Het
Kcnma1	A	C	14: 23,337,029	S982A	probably damaging	Het
Khdrbs3	T	A	15: 69,013,479		probably benign	Het
Kif23	A	T	9: 61,927,384	C426*	probably null	Het
Lmo7	G	T	14: 101,887,061	A319S	probably benign	Het
Ly6c1	T	A	15: 75,048,493	T7S	possibly damaging	Het
Magel2	G	A	7: 62,379,096	V583I	unknown	Het
Mamdc4	A	T	2: 25,567,232	W548R	probably damaging	Het
Mfsd2a	C	T	4: 122,956,816	R88Q	probably damaging	Het
Mkrn1	T	C	6: 39,405,803	T158A	probably benign	Het
Mroh2b	G	T	15: 4,925,684	D720Y	probably damaging	Het
Mycbp2	A	G	14: 103,248,403	V1041A	probably damaging	Het
Ncam2	A	T	16: 81,589,698	H655L	possibly damaging	Het
Npas2	T	C	1: 39,338,195	V546A	probably benign	Het
Nrxn3	G	A	12: 90,332,315	A400T	probably damaging	Het
Olfr1020	T	A	2: 85,850,400	V316E	probably benign	Het
Olfr1066	T	C	2: 86,455,473	H266R	probably benign	Het
Olfr139	A	T	11: 74,045,039	S78R	possibly damaging	Het
Oog3	G	T	4: 144,158,105	H420Q	possibly damaging	Het
Pak7	T	A	2: 136,116,637	H177L	probably benign	Het
Pcca	A	G	14: 122,887,065	I683V	probably benign	Het
Pea15a	T	C	1: 172,198,685	I90V	probably benign	Het
Plagl1	C	A	10: 13,128,658		probably benign	Het
Prmt1	A	G	7: 44,978,724	V237A	probably damaging	Het
Ptprz1	T	A	6: 23,027,834	Y910*	probably null	Het
Rasal3	T	A	17: 32,393,611	T757S	probably damaging	Het
Rbbp8	T	C	18: 11,727,166		probably benign	Het
S1pr1	A	G	3: 115,712,895	S17P	probably benign	Het
Scel	G	A	14: 103,541,985	V131M	probably damaging	Het
Snap29	T	A	16: 17,406,326	Y68*	probably null	Het
Spdl1	T	C	11: 34,822,646	T199A	probably benign	Het
Srbd1	T	C	17: 86,142,400	N14D	probably benign	Het
Ston1	G	A	17: 88,635,529	G121D	probably benign	Het
Syt16	G	A	12: 74,235,203	G367E	possibly damaging	Het
Tdpoz1	T	C	3: 93,671,403	T25A	possibly damaging	Het
Tmem182	T	A	1: 40,806,195	Y77N	probably damaging	Het
Tmprss11f	A	T	5: 86,539,768		probably benign	Het
Trp73	T	C	4: 154,081,445	T56A	probably damaging	Het
Trpm3	A	G	19: 22,982,583	K1194R	probably damaging	Het
Ttc39c	T	A	18: 12,697,878		probably null	Het
Ube4b	T	C	4: 149,383,797	D174G	probably benign	Het
Vmn1r211	A	T	13: 22,851,783	M238K	probably damaging	Het
Wsb2	T	A	5: 117,370,733	N77K	probably benign	Het
Xkr4	C	T	1: 3,671,095	R85Q	probably benign	Het
Zmynd11	T	A	13: 9,689,478		probably null	Het

Other mutations in Scn2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00088:Scn2a	APN	2	65764440	missense	probably benign
IGL00159:Scn2a	APN	2	65743090	missense	probably damaging	1.00
IGL00418:Scn2a	APN	2	65764522	missense	probably benign	0.43
IGL00753:Scn2a	APN	2	65683863	missense	possibly damaging	0.66
IGL00770:Scn2a	APN	2	65735853	missense	probably damaging	1.00
IGL00774:Scn2a	APN	2	65735853	missense	probably damaging	1.00
IGL00847:Scn2a	APN	2	65670734	missense	probably damaging	1.00
IGL01155:Scn2a	APN	2	65717748	missense	probably damaging	1.00
IGL01329:Scn2a	APN	2	65717508	missense	probably benign	0.05
IGL01537:Scn2a	APN	2	65715875	missense	probably benign	0.00
IGL01672:Scn2a	APN	2	65751934	missense	probably damaging	1.00
IGL01958:Scn2a	APN	2	65701829	missense	probably damaging	1.00
IGL02028:Scn2a	APN	2	65763658	missense	probably damaging	0.96
IGL02142:Scn2a	APN	2	65715838	missense	probably damaging	1.00
IGL02160:Scn2a	APN	2	65730116	missense	probably damaging	1.00
IGL02183:Scn2a	APN	2	65671603	missense	probably benign	0.20
IGL02341:Scn2a	APN	2	65688377	missense	probably damaging	1.00
IGL02504:Scn2a	APN	2	65683884	missense	probably benign	0.02
IGL02530:Scn2a	APN	2	65730178	missense	probably damaging	0.99
IGL02621:Scn2a	APN	2	65748879	splice site	probably benign
IGL02652:Scn2a	APN	2	65702038	missense	possibly damaging	0.82
IGL02966:Scn2a	APN	2	65701844	missense	possibly damaging	0.93
IGL03188:Scn2a	APN	2	65671653	missense	probably damaging	0.99
IGL03329:Scn2a	APN	2	65764629	missense	probably benign
IGL03336:Scn2a	APN	2	65688744	missense	probably damaging	1.00
IGL03391:Scn2a	APN	2	65764213	missense	probably damaging	1.00
PIT4280001:Scn2a	UTSW	2	65715730	missense	probably damaging	1.00
PIT4362001:Scn2a	UTSW	2	65683838	missense	probably benign	0.09
PIT4403001:Scn2a	UTSW	2	65711908	missense	probably damaging	1.00
PIT4520001:Scn2a	UTSW	2	65688419	missense	probably damaging	1.00
R0021:Scn2a	UTSW	2	65670515	missense	possibly damaging	0.51
R0141:Scn2a	UTSW	2	65711816	missense	probably benign	0.01
R0240:Scn2a	UTSW	2	65735774	missense	probably benign	0.32
R0240:Scn2a	UTSW	2	65735774	missense	probably benign	0.32
R0335:Scn2a	UTSW	2	65682091	missense	probably damaging	1.00
R0508:Scn2a	UTSW	2	65717842	missense	probably damaging	0.99
R0558:Scn2a	UTSW	2	65711925	missense	probably benign	0.26
R0600:Scn2a	UTSW	2	65701833	missense	possibly damaging	0.90
R0667:Scn2a	UTSW	2	65751996	missense	possibly damaging	0.91
R1178:Scn2a	UTSW	2	65686779	splice site	probably benign
R1244:Scn2a	UTSW	2	65763655	missense	probably damaging	0.98
R1386:Scn2a	UTSW	2	65688741	missense	probably damaging	1.00
R1434:Scn2a	UTSW	2	65701991	missense	possibly damaging	0.79
R1440:Scn2a	UTSW	2	65764594	missense	probably benign
R1448:Scn2a	UTSW	2	65683845	missense	probably benign	0.17
R1460:Scn2a	UTSW	2	65701843	missense	probably damaging	0.96
R1553:Scn2a	UTSW	2	65713836	nonsense	probably null
R1642:Scn2a	UTSW	2	65683697	missense	probably damaging	1.00
R1803:Scn2a	UTSW	2	65670767	splice site	probably null
R1981:Scn2a	UTSW	2	65690170	missense	probably damaging	1.00
R2068:Scn2a	UTSW	2	65752073	missense	probably benign	0.14
R2125:Scn2a	UTSW	2	65752079	nonsense	probably null
R2126:Scn2a	UTSW	2	65752079	nonsense	probably null
R2876:Scn2a	UTSW	2	65715897	missense	possibly damaging	0.64
R2878:Scn2a	UTSW	2	65688371	missense	probably damaging	1.00
R3113:Scn2a	UTSW	2	65748785	missense	possibly damaging	0.86
R3749:Scn2a	UTSW	2	65713771	missense	probably damaging	1.00
R3750:Scn2a	UTSW	2	65713771	missense	probably damaging	1.00
R3765:Scn2a	UTSW	2	65682710	missense	possibly damaging	0.51
R3850:Scn2a	UTSW	2	65682031	missense	probably benign	0.14
R4585:Scn2a	UTSW	2	65743051	splice site	probably null
R4586:Scn2a	UTSW	2	65743051	splice site	probably null
R4588:Scn2a	UTSW	2	65713767	missense	possibly damaging	0.76
R4622:Scn2a	UTSW	2	65752027	missense	probably benign	0.04
R5108:Scn2a	UTSW	2	65688630	missense	probably damaging	1.00
R5161:Scn2a	UTSW	2	65764591	missense	probably benign	0.00
R5235:Scn2a	UTSW	2	65752011	missense	probably damaging	1.00
R5464:Scn2a	UTSW	2	65701756	missense	probably damaging	1.00
R5586:Scn2a	UTSW	2	65707295	nonsense	probably null
R5630:Scn2a	UTSW	2	65726365	missense	probably damaging	1.00
R5715:Scn2a	UTSW	2	65717584	missense	probably benign	0.27
R5730:Scn2a	UTSW	2	65682538	nonsense	probably null
R5734:Scn2a	UTSW	2	65717722	missense	possibly damaging	0.49
R5779:Scn2a	UTSW	2	65764483	missense	probably benign	0.00
R6133:Scn2a	UTSW	2	65743104	missense	probably benign	0.35
R6547:Scn2a	UTSW	2	65715897	missense	probably benign	0.29
R6549:Scn2a	UTSW	2	65764674	missense	probably benign	0.05
R6818:Scn2a	UTSW	2	65688669	nonsense	probably null
R6999:Scn2a	UTSW	2	65682109	missense	probably benign
R7069:Scn2a	UTSW	2	65764606	missense	probably benign	0.00
R7073:Scn2a	UTSW	2	65728443	missense	probably benign	0.00
R7125:Scn2a	UTSW	2	65763933	missense	probably damaging	1.00
R7178:Scn2a	UTSW	2	65748853	nonsense	probably null
R7179:Scn2a	UTSW	2	65701979	missense	probably damaging	1.00
R7203:Scn2a	UTSW	2	65748319	missense	probably benign	0.01
R7227:Scn2a	UTSW	2	65752023	missense	probably damaging	0.98
R7269:Scn2a	UTSW	2	65763769	missense	probably damaging	1.00
R7358:Scn2a	UTSW	2	65682506	nonsense	probably null
R7388:Scn2a	UTSW	2	65688654	missense	probably damaging	1.00
R7491:Scn2a	UTSW	2	65702008	missense	probably damaging	0.99
R7619:Scn2a	UTSW	2	65715903	missense	probably damaging	1.00
R7695:Scn2a	UTSW	2	65711907	missense	probably damaging	0.99
R7735:Scn2a	UTSW	2	65763669	missense	probably benign	0.40
R7911:Scn2a	UTSW	2	65682083	missense	probably null	1.00
R8096:Scn2a	UTSW	2	65764022	missense	probably damaging	0.98
R8333:Scn2a	UTSW	2	65683847	missense	probably benign	0.01
R8416:Scn2a	UTSW	2	65681001	missense	probably benign	0.00
R8850:Scn2a	UTSW	2	65688386	missense	probably damaging	1.00
R8897:Scn2a	UTSW	2	65715658	critical splice acceptor site	probably null
R8977:Scn2a	UTSW	2	65763670	missense	probably damaging	0.99
R8992:Scn2a	UTSW	2	65763898	missense	probably damaging	1.00
R9190:Scn2a	UTSW	2	65681002	missense	probably benign	0.00
R9206:Scn2a	UTSW	2	65717787	missense	probably damaging	1.00
R9355:Scn2a	UTSW	2	65764089	missense	probably damaging	1.00
Z1176:Scn2a	UTSW	2	65751868	missense	possibly damaging	0.84
Z1177:Scn2a	UTSW	2	65717735	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- ACCTAGAGTCTCTATTCATGTGTG -3'
(R):5'- CCAACTGAGCTGCTATTGGG -3'

Sequencing Primer
(F):5'- CATCTTTAGGATATGAACACTTGGGG -3'
(R):5'- GGATCATTCCTAATTTCTCCAGACTG -3'

Posted On

2014-08-25