Mutagenetix > Incidental Mutation

Incidental Mutation 'R9355:Scn2a'

708308

Institutional Source

Beutler Lab

Gene Symbol

Scn2a

Ensembl Gene

ENSMUSG00000075318

Gene Name

sodium channel, voltage-gated, type II, alpha

Synonyms

A230052E19Rik, Scn2a1, Nav1.2

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9355 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

65620771-65767447 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 65764089 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 1761 (I1761F)

Ref Sequence

ENSEMBL: ENSMUSP00000028377 (fasta)

Gene Model

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

AlphaFold

B1AWN6

Predicted Effect

probably damaging
Transcript: ENSMUST00000028377
AA Change: I1761F

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

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: I1761F

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: I1761F

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

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: I1761F

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: I1761F

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

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: I1761F

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: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
AI314180	A	T	4: 58,844,114	S551T	probably benign	Het
Ano9	A	G	7: 141,101,904	V747A	probably benign	Het
Arfgef1	G	A	1: 10,199,775	P383L	probably benign	Het
Arhgef4	A	G	1: 34,810,549	E407G	probably benign	Het
Astn1	C	T	1: 158,684,151	L1188F	probably damaging	Het
Atg2b	G	A	12: 105,670,721	P179S	possibly damaging	Het
Bcl9l	G	A	9: 44,507,703	R983H	probably benign	Het
Bmp2k	T	A	5: 97,063,507	Y511*	probably null	Het
C1galt1	G	T	6: 7,866,474	V107F	probably damaging	Het
Car3	T	A	3: 14,863,604	N11K		Het
Ccdc170	A	G	10: 4,558,695	R640G	probably benign	Het
Cep126	A	G	9: 8,100,037	V832A	possibly damaging	Het
Ces1h	C	T	8: 93,374,521	V49I		Het
Clasp2	T	A	9: 113,835,241	V310D	probably damaging	Het
Comp	C	T	8: 70,376,049	T177M	probably benign	Het
Coro1c	T	C	5: 113,865,665	S98G	probably damaging	Het
Cpa6	C	T	1: 10,409,295	V238I	probably benign	Het
Crebrf	T	C	17: 26,743,120	F397S	probably damaging	Het
Dcpp1	C	A	17: 23,881,013	Q3K	possibly damaging	Het
Dzip1l	A	G	9: 99,661,091	D533G	possibly damaging	Het
Epha5	T	C	5: 84,106,031	E524G	probably damaging	Het
Epha7	A	G	4: 28,935,806	Y476C	probably damaging	Het
Erich5	G	T	15: 34,470,855	V77F	probably damaging	Het
Fat4	A	G	3: 38,981,898	Y3233C	probably damaging	Het
Ggt1	T	A	10: 75,585,882	V521E	probably benign	Het
Gm37596	T	C	3: 93,693,000	T21A	possibly damaging	Het
Gm5431	A	G	11: 48,894,448	Y89H	probably damaging	Het
Gm5624	A	T	14: 44,561,815	L95*	probably null	Het
Gphn	A	G	12: 78,492,194	T205A	probably damaging	Het
Grik5	C	A	7: 25,068,172	A28S	possibly damaging	Het
H2-K1	A	G	17: 33,997,146	S300P	probably benign	Het
H2-Oa	T	C	17: 34,094,749	L227P	possibly damaging	Het
Hhip	T	C	8: 80,051,604	N99S	probably damaging	Het
Hmcn2	A	T	2: 31,438,290	M4328L	probably benign	Het
Htt	A	T	5: 34,895,903	M2527L	probably benign	Het
Impdh2	A	T	9: 108,565,203	H466L	probably benign	Het
Itgae	G	A	11: 73,116,080	G384D	probably damaging	Het
Krt90	T	C	15: 101,553,279	S496G	unknown	Het
Krtap5-5	A	G	7: 142,229,377	S179P	unknown	Het
Lif	C	T	11: 4,269,044	R63W	probably damaging	Het
Lrrc10	T	C	10: 117,045,976	V185A	probably damaging	Het
Lrrc27	A	C	7: 139,242,732	Q513P	probably damaging	Het
Ltbp2	G	A	12: 84,791,090	P1192L	probably benign	Het
Map2k3	T	C	11: 60,932,229	S3P	possibly damaging	Het
Mc2r	T	C	18: 68,408,124	T33A	probably benign	Het
Mefv	T	A	16: 3,708,018	D795V	probably damaging	Het
Megf6	A	T	4: 154,253,825	R451W	probably damaging	Het
Mrpl21	G	A	19: 3,286,937	V103M	probably damaging	Het
Mtmr14	GCCGCCGCCTCGGCGGGTTCCACCGCCTCGTCGGGCAGCCCGCCGCCTC	GCCGCCGCCTC	6: 113,237,987		probably null	Het
Myom1	T	C	17: 71,077,893	S760P	probably damaging	Het
Ndst4	A	G	3: 125,609,597	Y451C	probably damaging	Het
Nkain4	T	C	2: 180,935,982	N193S	possibly damaging	Het
Olfr1198	A	T	2: 88,746,405	I161N	probably damaging	Het
Olfr1330	G	A	4: 118,893,587	S168N	probably benign	Het
Olfr393	A	G	11: 73,847,817	F103L	probably damaging	Het
Olfr601	T	C	7: 103,358,918	H92R	probably benign	Het
Opa1	T	A	16: 29,613,989	L490H	probably damaging	Het
Opcml	A	C	9: 28,903,354	I301L	probably benign	Het
Pabpc1l	T	C	2: 164,042,549	L402P	probably benign	Het
Palld	C	T	8: 61,516,657	R1211H	unknown	Het
Peak1	G	T	9: 56,260,170	A158E	probably damaging	Het
Ppfibp2	C	T	7: 107,722,962	P406L	probably benign	Het
Qpctl	T	C	7: 19,141,221	H362R	probably damaging	Het
Ripor2	A	G	13: 24,701,711	H643R	probably benign	Het
Scn11a	A	T	9: 119,755,094	L1485Q	probably damaging	Het
Scrn3	A	G	2: 73,335,733	D370G	probably benign	Het
Sec24b	A	T	3: 129,993,840	F877Y	possibly damaging	Het
Slc35f3	T	C	8: 126,382,228	I172T	probably damaging	Het
Smc3	T	C	19: 53,634,113		probably null	Het
Smpd3	C	T	8: 106,265,193	V243M	probably damaging	Het
Sos1	T	A	17: 80,415,050	I856F	possibly damaging	Het
Sp2	A	T	11: 96,961,405	L231H	possibly damaging	Het
Syne1	T	C	10: 5,368,255	Y457C	probably damaging	Het
Tekt5	T	C	16: 10,395,404	T6A	possibly damaging	Het
Tln2	G	T	9: 67,355,247	T574K	possibly damaging	Het
Tmem161a	T	C	8: 70,181,171	S313P	probably damaging	Het
Trmt12	G	A	15: 58,872,975	C74Y	probably damaging	Het
Trpc6	A	G	9: 8,649,472	D561G	probably benign	Het
Ttn	A	G	2: 76,870,425	V62A		Het
Tubgcp5	T	C	7: 55,817,429		probably null	Het
Unc13a	C	T	8: 71,645,731	V1137M	possibly damaging	Het
Zfp729a	A	G	13: 67,619,396	C905R	probably damaging	Het
Zfp735	A	G	11: 73,711,536	I435M	probably benign	Het
Zswim4	C	A	8: 84,229,058	G271W	probably damaging	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
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
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'- AGTTGGGATTGATGACATGTTCAAC -3'
(R):5'- GCTGCAAAGTCAGAGAGCTTG -3'

Sequencing Primer
(F):5'- CAACTTTGAGACCTTTGGCAAC -3'
(R):5'- GCTTGCAGAACTCTATGAACTGG -3'

Posted On

2022-04-18