Mutagenetix > Incidental Mutation

Incidental Mutation 'R1553:Scn2a'

170055

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

039592-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1553 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

65620771-65767447 bp(+) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

C to T at 65713836 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Stop codon at position 854 (R854*)

Ref Sequence

ENSEMBL: ENSMUSP00000143882 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028377] [ENSMUST00000100067] [ENSMUST00000200829] [ENSMUST00000202508]

AlphaFold

B1AWN6

Predicted Effect

probably null
Transcript: ENSMUST00000028377
AA Change: R854*

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: R854*

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: R854*

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: R854*

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: R854*

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: R854*

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

Predicted Effect

probably benign
Transcript: ENSMUST00000202162

Predicted Effect

probably benign
Transcript: ENSMUST00000202508

SMART Domains

Protein: ENSMUSP00000143958
Gene: ENSMUSG00000075318

Domain	Start	End	E-Value	Type
Pfam:Na_trans_assoc	1	106	1.9e-19	PFAM

Coding Region Coverage

1x: 99.1%
3x: 98.2%
10x: 96.0%
20x: 92.1%

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: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb8	G	T	5: 24,408,750	A649S	probably damaging	Het
Adam6a	T	A	12: 113,545,215	C403S	probably damaging	Het
Adgrg3	T	C	8: 95,040,268	F417S	possibly damaging	Het
Ago1	T	C	4: 126,440,401	E439G	probably damaging	Het
Alox15	A	G	11: 70,349,632	V241A	possibly damaging	Het
Arhgap6	A	G	X: 169,265,484	H566R	probably damaging	Het
Asap1	A	T	15: 64,152,852	F345I	probably benign	Het
Atp1b2	A	G	11: 69,602,852	Y134H	probably damaging	Het
Atp8b3	G	A	10: 80,532,542	T199M	probably damaging	Het
Calb1	A	T	4: 15,895,656	S115C	probably damaging	Het
Ccdc68	A	T	18: 69,940,121	I47F	probably damaging	Het
Cdc42bpa	A	T	1: 180,093,975	N560I	probably benign	Het
Cdhr3	T	C	12: 33,042,371	D747G	probably benign	Het
Cdk5rap1	T	G	2: 154,352,251	N378T	probably damaging	Het
Chil4	T	G	3: 106,203,690	N296T	probably benign	Het
Cryaa	G	A	17: 31,679,559	V87I	probably damaging	Het
Csk	G	A	9: 57,630,942	L28F	probably damaging	Het
Cspp1	A	G	1: 10,085,897	N444D	possibly damaging	Het
Cyp2j8	A	G	4: 96,475,557	Y290H	probably benign	Het
Eps8l1	A	T	7: 4,477,449	D563V	probably damaging	Het
Fam111a	A	T	19: 12,587,318	S144C	possibly damaging	Het
Fam135a	A	T	1: 24,021,870	S1145R	probably damaging	Het
Fpr2	T	A	17: 17,893,594	V284D	possibly damaging	Het
Furin	A	G	7: 80,398,592		probably null	Het
Gatd1	T	C	7: 141,409,893	T135A	probably benign	Het
Gdf3	A	G	6: 122,609,765	S68P	probably benign	Het
Gm6871	T	C	7: 41,546,398	H305R	probably benign	Het
Grip1	A	G	10: 120,054,851	S917G	probably damaging	Het
Hdac10	T	A	15: 89,125,515	E388V	possibly damaging	Het
Hectd1	T	C	12: 51,773,878	N1176S	probably damaging	Het
Hectd4	A	G	5: 121,349,259	D3439G	probably benign	Het
Kcna4	T	C	2: 107,296,687	Y589H	probably benign	Het
Kcnk5	A	T	14: 20,142,394	L233Q	probably damaging	Het
Kcnt1	T	C	2: 25,900,385	I453T	probably damaging	Het
Kifc3	A	G	8: 95,106,542	I440T	possibly damaging	Het
Krt10	C	A	11: 99,385,980	G40*	probably null	Het
Lce1i	A	T	3: 92,777,795	C25S	unknown	Het
Met	A	G	6: 17,491,461	N74S	probably benign	Het
Naa35	G	A	13: 59,618,279		probably null	Het
Naalad2	T	C	9: 18,378,669	N221S	probably benign	Het
Nolc1	AGCG	AGCGGCG	19: 46,081,375		probably benign	Het
Nsmf	T	C	2: 25,060,259	V181A	probably damaging	Het
Nwd2	T	A	5: 63,800,505	S393T	probably benign	Het
Olfr530	T	A	7: 140,373,038	T191S	probably damaging	Het
Olfr575	T	A	7: 102,955,218	I128L	possibly damaging	Het
Olfr709-ps1	A	T	7: 106,926,994	V155E	possibly damaging	Het
Papola	T	A	12: 105,820,410	S453R	probably benign	Het
Paqr9	A	G	9: 95,560,209	N84S	probably damaging	Het
Pde5a	T	C	3: 122,778,936	V290A	probably benign	Het
Prf1	T	C	10: 61,303,169	V302A	probably damaging	Het
Psg18	T	C	7: 18,353,481	Y84C	probably benign	Het
Rasgrf2	C	T	13: 91,890,664	R1021H	probably damaging	Het
Rnf114	G	T	2: 167,512,602	R201L	possibly damaging	Het
Rp1l1	A	G	14: 64,031,894	E1643G	probably benign	Het
Scg3	T	A	9: 75,669,304	E263V	probably null	Het
Setdb2	T	C	14: 59,417,485	K319E	probably benign	Het
Stub1	A	T	17: 25,832,123	V95E	probably damaging	Het
Tas2r140	T	A	6: 133,055,508	N96Y	probably damaging	Het
Tecta	T	A	9: 42,348,186	D1467V	probably damaging	Het
Tenm3	T	A	8: 48,236,421	T2044S	probably damaging	Het
Tlr2	T	A	3: 83,837,463	M438L	probably benign	Het
Tmem179	T	C	12: 112,504,660	Y106C	probably benign	Het
Tspan7	A	G	X: 10,585,615	H187R	probably benign	Het
Ttn	T	C	2: 76,927,275	D3332G	probably damaging	Het
Upp2	T	C	2: 58,790,140	F326S	probably damaging	Het
Usp2	T	A	9: 44,092,155	D224E	probably damaging	Het
Vmn1r5	T	A	6: 56,985,498	F53I	probably benign	Het
Wapl	T	A	14: 34,729,190	L727H	probably damaging	Het
Wipf1	T	C	2: 73,437,526	D176G	possibly damaging	Het
Xpnpep1	G	T	19: 53,006,338	D243E	probably benign	Het
Zfp616	A	T	11: 74,083,918	I429F	possibly damaging	Het
Zfyve26	G	A	12: 79,287,761	P161L	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
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
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'- ACTGGGATCTTCACCGCAGAAATG -3'
(R):5'- CCAAGGTCGTAATGGAAGCTCTCAC -3'

Sequencing Primer
(F):5'- GCCTTAGTTTAATGGAACTCGGC -3'
(R):5'- CAATCTGGCTTGATATGAGACTCC -3'

Posted On

2014-04-13