Mutagenetix > Incidental Mutation

Incidental Mutation 'R2125:Scn2a'

229725

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

040128-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2125 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

65620771-65767447 bp(+) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 65752079 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Stop codon at position 1590 (Y1590*)

Ref Sequence

ENSEMBL: ENSMUSP00000143882 (fasta)

Gene Model

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

AlphaFold

B1AWN6

Predicted Effect

probably null
Transcript: ENSMUST00000028377
AA Change: Y1590*

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: Y1590*

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: Y1590*

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: Y1590*

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 null
Transcript: ENSMUST00000200829
AA Change: Y1590*

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: Y1590*

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: 99.2%
3x: 98.6%
10x: 97.3%
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: 89 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9530053A07Rik	A	T	7: 28,158,022	Y2265F	probably benign	Het
Aadac	A	G	3: 60,039,645	T255A	possibly damaging	Het
Abcb10	A	C	8: 123,965,092	V378G	probably benign	Het
Ackr2	C	T	9: 121,908,786	R76*	probably null	Het
Acly	T	C	11: 100,523,496	T35A	probably benign	Het
Acp7	A	C	7: 28,629,549	F69V	probably damaging	Het
Acsl3	T	A	1: 78,681,961	I110N	probably damaging	Het
Adam5	C	T	8: 24,815,118	V107M	probably damaging	Het
Adck2	T	C	6: 39,575,142	V281A	probably benign	Het
Adgrv1	A	G	13: 81,419,535	V5173A	probably benign	Het
Adgrv1	A	T	13: 81,419,950	S5035T	probably benign	Het
AI314180	T	C	4: 58,833,978	H834R	probably benign	Het
Arl10	T	A	13: 54,579,124		probably null	Het
B3gnt3	A	G	8: 71,693,358	W176R	probably damaging	Het
B4galt4	T	C	16: 38,765,938	I3T	probably damaging	Het
Casr	T	C	16: 36,495,252	I819V	possibly damaging	Het
Cdh1	T	C	8: 106,656,840	V237A	probably damaging	Het
Col22a1	G	A	15: 71,848,577	R605C	unknown	Het
Crlf3	A	G	11: 80,059,255	V183A	probably benign	Het
Crtac1	C	A	19: 42,323,732	V181L	probably damaging	Het
Dclk2	C	T	3: 86,805,639	R503Q	possibly damaging	Het
Dnah12	A	T	14: 26,724,458	R725*	probably null	Het
Dnhd1	A	T	7: 105,677,971	H709L	probably benign	Het
Dopey1	A	G	9: 86,521,046	Y1431C	probably damaging	Het
Eif2ak4	A	T	2: 118,422,123	H392L	probably benign	Het
Entpd3	T	C	9: 120,555,654	I99T	probably damaging	Het
Epha6	T	C	16: 59,682,688	D952G	probably damaging	Het
Exoc6	T	C	19: 37,590,941	L429P	probably damaging	Het
F13a1	A	G	13: 36,892,841	S625P	probably benign	Het
Fcho2	T	C	13: 98,775,898	N240S	possibly damaging	Het
Fcrl6	C	T	1: 172,599,248	V44M	probably benign	Het
Fmo6	A	T	1: 162,929,958	M82K	possibly damaging	Het
Gabrr2	T	G	4: 33,095,548	I479R	probably damaging	Het
Gm14409	C	A	2: 177,265,402	C101F	probably damaging	Het
Gnl2	T	A	4: 125,053,485	F633L	probably benign	Het
Greb1l	C	T	18: 10,511,422	S648F	probably damaging	Het
Gsap	T	A	5: 21,242,813	C290S	probably damaging	Het
Gusb	A	G	5: 129,999,447	V268A	probably benign	Het
H2-D1	G	A	17: 35,264,115		probably null	Het
Hebp2	T	A	10: 18,541,260	E164D	probably benign	Het
Higd1a	A	T	9: 121,850,247	I58N	probably damaging	Het
Hoxc13	G	T	15: 102,927,223	R262L	probably damaging	Het
Ifih1	A	G	2: 62,623,467	V218A	probably benign	Het
Impg2	T	A	16: 56,265,064	Y1045N	probably damaging	Het
Kcnk1	A	G	8: 125,995,656	E66G	probably damaging	Het
Klkb1	A	G	8: 45,275,504	V406A	possibly damaging	Het
Klra10	G	A	6: 130,279,278	R138W	probably damaging	Het
Lama2	A	C	10: 27,044,453	Y193*	probably null	Het
Larp7	T	C	3: 127,543,130	T428A	probably benign	Het
Lipg	T	C	18: 74,945,885	N432S	probably benign	Het
Loxl1	T	C	9: 58,293,712	D489G	probably damaging	Het
Lrguk	A	G	6: 34,092,902	K571E	probably benign	Het
Map3k13	C	T	16: 21,892,144	T59I	probably benign	Het
Mertk	T	A	2: 128,762,138	D397E	probably benign	Het
Mgat3	G	A	15: 80,211,886	V305I	probably benign	Het
Mkl2	T	C	16: 13,400,804	V449A	possibly damaging	Het
Mybpc1	G	A	10: 88,573,437	Q66*	probably null	Het
Myo3a	A	G	2: 22,578,174	D480G	probably benign	Het
Ndufaf3	C	T	9: 108,566,737	R31Q	probably benign	Het
Neb	T	C	2: 52,310,638	Y343C	probably damaging	Het
Nrxn3	A	G	12: 89,260,520		probably null	Het
Olfr1090	A	T	2: 86,754,452	N95K	probably benign	Het
Olfr1257	A	G	2: 89,881,638	M271V	probably benign	Het
Pcsk4	T	C	10: 80,323,879	M379V	probably benign	Het
Pdzd2	A	T	15: 12,373,590	V2153E	probably benign	Het
Pkd2l1	T	C	19: 44,154,500	D427G	possibly damaging	Het
Plcd4	A	G	1: 74,565,152	Y763C	probably damaging	Het
Plekhh1	T	C	12: 79,079,000	F1270S	probably damaging	Het
Pmfbp1	T	C	8: 109,520,273	V259A	probably damaging	Het
Ptprg	T	C	14: 12,179,283	S767P	possibly damaging	Het
Rabl3	T	G	16: 37,556,813		probably null	Het
Rffl	T	A	11: 82,818,438	H53L	probably damaging	Het
Rif1	GCCACCA	GCCA	2: 52,110,324		probably benign	Het
Rtl1	C	T	12: 109,593,921	V495I	possibly damaging	Het
Scaf11	A	T	15: 96,419,315	D789E	possibly damaging	Het
Siglech	T	A	7: 55,771,686	F190I	probably benign	Het
Slc22a22	C	A	15: 57,254,240	A302S	probably damaging	Het
Slc46a3	T	A	5: 147,879,144	T458S	probably benign	Het
Spta1	G	T	1: 174,208,344	R1072L	possibly damaging	Het
Tbx5	A	G	5: 119,836,923	T4A	probably benign	Het
Tdrd5	T	C	1: 156,276,573	R528G	probably damaging	Het
Tfip11	T	C	5: 112,335,663	V648A	possibly damaging	Het
Thumpd3	T	C	6: 113,066,788	V388A	probably benign	Het
Tmem131l	C	T	3: 83,942,751		probably null	Het
Ttf2	C	A	3: 100,948,193	Q895H	possibly damaging	Het
Ttn	A	T	2: 76,890,092		probably null	Het
Vmn2r13	A	G	5: 109,158,192	S507P	probably benign	Het
Vtn	A	G	11: 78,500,223	T210A	probably damaging	Het
Znhit2	A	G	19: 6,062,061	T279A	probably benign	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
R2002:Scn2a	UTSW	2	65682083	missense	probably null	1.00
R2068:Scn2a	UTSW	2	65752073	missense	probably benign	0.14
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
R9452:Scn2a	UTSW	2	65764819	missense	probably benign
R9529:Scn2a	UTSW	2	65764588	missense	probably damaging	0.99
R9567:Scn2a	UTSW	2	65688630	missense	probably damaging	1.00
R9569:Scn2a	UTSW	2	65730278	missense	probably damaging	1.00
R9657:Scn2a	UTSW	2	65735688	missense	probably damaging	1.00
R9715:Scn2a	UTSW	2	65748805	missense	possibly damaging	0.93
R9761:Scn2a	UTSW	2	65735686	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'- TTGACATCAGCATCATGATCCTC -3'
(R):5'- AGGAATGGACTATTCGGCTTTATCTG -3'

Sequencing Primer
(F):5'- CATCTGCCTCAACATGGTGAC -3'
(R):5'- AGTTAGGGTCTCACCATGTTGCTC -3'

Posted On

2014-09-17