Mutagenetix > Incidental Mutations

Incidental Mutation 'R2157:Scn9a'

234883

Institutional Source

Beutler Lab

Gene Symbol

Scn9a

Ensembl Gene

ENSMUSG00000075316

Gene Name

sodium channel, voltage-gated, type IX, alpha

Synonyms

PN1

MMRRC Submission

040160-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R2157 (G1)

Quality Score

202

Status

Validated

Chromosome

Chromosomal Location

66480080-66634962 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 66536325 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 705 (S705P)

Ref Sequence

ENSEMBL: ENSMUSP00000126528 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000100063] [ENSMUST00000100064] [ENSMUST00000112354] [ENSMUST00000164384] [ENSMUST00000169900]

Predicted Effect

probably damaging
Transcript: ENSMUST00000100063
AA Change: S696P

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

SMART Domains

Protein: ENSMUSP00000097641
Gene: ENSMUSG00000075316
AA Change: S696P

Domain	Start	End	E-Value	Type
low complexity region	29	49	N/A	INTRINSIC
Pfam:Ion_trans	154	403	9.5e-78	PFAM
coiled coil region	404	442	N/A	INTRINSIC
Pfam:DUF3451	465	685	1.3e-62	PFAM
Pfam:Ion_trans	768	957	9.9e-48	PFAM
Pfam:Na_trans_assoc	972	1191	2.9e-72	PFAM
low complexity region	1203	1214	N/A	INTRINSIC
Pfam:Ion_trans	1217	1445	2.8e-55	PFAM
PDB:1BYY\|A	1447	1499	9e-27	PDB
Pfam:Ion_trans	1538	1748	3.4e-52	PFAM
Pfam:PKD_channel	1599	1755	1.1e-7	PFAM
IQ	1877	1899	1.03e-3	SMART
low complexity region	1956	1972	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000100064
AA Change: S705P

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

SMART Domains

Protein: ENSMUSP00000097642
Gene: ENSMUSG00000075316
AA Change: S705P

Domain	Start	End	E-Value	Type
low complexity region	29	49	N/A	INTRINSIC
Pfam:Ion_trans	125	412	2.2e-84	PFAM
low complexity region	433	446	N/A	INTRINSIC
Pfam:Na_trans_cytopl	483	693	7.5e-76	PFAM
Pfam:Ion_trans	742	977	4.1e-57	PFAM
Pfam:Na_trans_assoc	981	1185	1.4e-58	PFAM
Pfam:Ion_trans	1189	1466	7e-67	PFAM
Pfam:Ion_trans	1512	1769	1e-55	PFAM
Pfam:PKD_channel	1605	1763	2.6e-7	PFAM
IQ	1886	1908	1.03e-3	SMART
low complexity region	1965	1981	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000112354
AA Change: S694P

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

SMART Domains

Protein: ENSMUSP00000107973
Gene: ENSMUSG00000075316
AA Change: S694P

Domain	Start	End	E-Value	Type
low complexity region	29	49	N/A	INTRINSIC
Pfam:Ion_trans	154	401	1.2e-77	PFAM
coiled coil region	402	449	N/A	INTRINSIC
Pfam:DUF3451	463	683	1.3e-62	PFAM
Pfam:Ion_trans	766	955	9.9e-48	PFAM
Pfam:Na_trans_assoc	970	1189	2.9e-72	PFAM
low complexity region	1201	1212	N/A	INTRINSIC
Pfam:Ion_trans	1215	1443	2.8e-55	PFAM
PDB:1BYY\|A	1445	1497	7e-29	PDB
Pfam:Ion_trans	1536	1746	3.4e-52	PFAM
Pfam:PKD_channel	1597	1753	1.1e-7	PFAM
IQ	1875	1897	1.03e-3	SMART
low complexity region	1954	1970	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141149

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151234

Predicted Effect

probably damaging
Transcript: ENSMUST00000164384
AA Change: S705P

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

SMART Domains

Protein: ENSMUSP00000126528
Gene: ENSMUSG00000075316
AA Change: S705P

Domain	Start	End	E-Value	Type
low complexity region	29	49	N/A	INTRINSIC
Pfam:Ion_trans	154	401	1.1e-77	PFAM
coiled coil region	402	449	N/A	INTRINSIC
Pfam:DUF3451	463	694	4.2e-66	PFAM
Pfam:Ion_trans	777	966	8.8e-48	PFAM
Pfam:Na_trans_assoc	981	1200	6e-72	PFAM
low complexity region	1212	1223	N/A	INTRINSIC
Pfam:Ion_trans	1226	1454	2.5e-55	PFAM
PDB:1BYY\|A	1456	1508	6e-29	PDB
Pfam:Ion_trans	1547	1757	3e-52	PFAM
Pfam:PKD_channel	1608	1764	8.1e-8	PFAM
IQ	1886	1908	1.03e-3	SMART
low complexity region	1965	1981	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000169900
AA Change: S694P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000131711
Gene: ENSMUSG00000075316
AA Change: S694P

Domain	Start	End	E-Value	Type
low complexity region	29	49	N/A	INTRINSIC
Pfam:Ion_trans	154	401	3.7e-78	PFAM
coiled coil region	402	449	N/A	INTRINSIC
Pfam:DUF3451	463	683	1.3e-62	PFAM
Pfam:Ion_trans	766	955	9.9e-48	PFAM
Pfam:Na_trans_assoc	970	1189	2.9e-72	PFAM
low complexity region	1201	1212	N/A	INTRINSIC
Pfam:Ion_trans	1215	1443	2.8e-55	PFAM
PDB:1BYY\|A	1445	1497	7e-29	PDB
Pfam:Ion_trans	1536	1746	3.4e-52	PFAM
Pfam:PKD_channel	1597	1753	1.1e-7	PFAM
IQ	1875	1897	1.03e-3	SMART
low complexity region	1954	1970	N/A	INTRINSIC

Meta Mutation Damage Score

0.3292

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.7%

Validation Efficiency

100% (80/80)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit prenatal/neonatal lethality. Mice homozygous for a knock-in allele exhibit increased susceptibility to electrically induced seizures. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310022B05Rik	A	T	8: 124,651,429		probably benign	Het
4930590J08Rik	A	G	6: 91,917,698		probably null	Het
4930590J08Rik	T	A	6: 91,942,487	M709K	possibly damaging	Het
A930011G23Rik	T	G	5: 99,232,097	I394L	probably damaging	Het
Abca13	A	C	11: 9,577,170	M4528L	probably damaging	Het
Abcb1b	G	A	5: 8,824,791	A484T	probably benign	Het
Actn1	A	T	12: 80,173,117	M660K	probably benign	Het
Adgra3	G	T	5: 50,001,941	N322K	possibly damaging	Het
Ahnak	A	G	19: 9,000,684	I56V	possibly damaging	Het
Amotl2	A	G	9: 102,730,589		probably benign	Het
Apoa1	T	C	9: 46,229,173	V34A	probably damaging	Het
Arrdc1	G	A	2: 24,926,975	A113V	probably damaging	Het
As3mt	A	G	19: 46,707,792	D13G	probably benign	Het
C77080	C	T	4: 129,224,124	R249H	possibly damaging	Het
Cald1	A	G	6: 34,686,041	Q13R	possibly damaging	Het
Ccdc28a	G	A	10: 18,230,455	T41I	probably benign	Het
Ccdc30	A	T	4: 119,333,724		probably benign	Het
Cct2	T	C	10: 117,062,809		probably benign	Het
Cdh12	T	C	15: 21,583,787	I571T	possibly damaging	Het
Cdh15	G	A	8: 122,862,024	R279Q	probably damaging	Het
Ckm	T	C	7: 19,421,354	S372P	probably benign	Het
Comp	C	T	8: 70,379,570	Q554*	probably null	Het
Csf2ra	T	C	19: 61,227,071	T70A	probably benign	Het
Csmd3	T	C	15: 47,695,787	E2256G	probably damaging	Het
Dicer1	A	T	12: 104,702,949	V1158D	probably benign	Het
Dner	A	G	1: 84,383,938	F650S	possibly damaging	Het
Dnm3	T	C	1: 162,307,893	N437S	possibly damaging	Het
Dpy19l2	A	T	9: 24,584,632	C597S	probably benign	Het
Dpy19l2	T	C	9: 24,680,780	I176V	probably benign	Het
Edf1	T	C	2: 25,558,031		probably null	Het
Enpp3	A	G	10: 24,776,878	F727S	probably damaging	Het
Epb42	C	T	2: 121,021,762	M583I	probably benign	Het
Foxred1	A	G	9: 35,205,363	F117S	probably damaging	Het
Fstl5	T	A	3: 76,708,065	M811K	possibly damaging	Het
Gm5117	A	T	8: 31,738,194		noncoding transcript	Het
Gm6803	A	T	12: 88,018,711	S21T	unknown	Het
Gpm6a	T	C	8: 55,058,798	S236P	probably damaging	Het
Grik1	G	A	16: 88,056,124	A57V	probably damaging	Het
Hdgfl2	G	A	17: 56,098,691	V476I	possibly damaging	Het
Il17b	G	T	18: 61,690,368	W91L	probably damaging	Het
Jph4	C	A	14: 55,113,527	R344L	probably benign	Het
Map3k21	A	G	8: 125,937,266	D522G	probably benign	Het
Mast2	A	G	4: 116,322,283	L398S	probably damaging	Het
Mbtd1	A	G	11: 93,910,388	T132A	probably benign	Het
Mbtps1	G	T	8: 119,542,727	T208K	probably benign	Het
Mr1	A	G	1: 155,146,630		probably null	Het
Mthfsd	G	A	8: 121,101,501	L140F	probably damaging	Het
Mybpc2	C	G	7: 44,509,845	D594H	possibly damaging	Het
Nalcn	T	C	14: 123,409,752	M570V	probably benign	Het
Ncam2	T	C	16: 81,490,389	I397T	probably damaging	Het
Ndufs4	C	T	13: 114,316,978	V75I	probably damaging	Het
Nek4	T	A	14: 30,979,968		probably null	Het
Nfatc1	G	T	18: 80,635,845	A762D	possibly damaging	Het
Npc1	A	G	18: 12,191,809	I1209T	probably damaging	Het
Olfr1206	A	T	2: 88,864,869	N88I	probably benign	Het
Olfr370	T	C	8: 83,541,621	I159T	probably benign	Het
Pak7	T	C	2: 136,100,957	D421G	probably damaging	Het
Pias1	A	G	9: 62,912,830	V285A	possibly damaging	Het
Pigg	T	A	5: 108,318,889	I212N	probably damaging	Het
Plcd3	A	T	11: 103,071,148	C711S	probably benign	Het
Plscr5	G	A	9: 92,198,497	R12K	probably benign	Het
Plxna4	T	C	6: 32,516,974	I236V	probably benign	Het
Ppp1r26	T	C	2: 28,452,358	F667L	probably benign	Het
Pqlc2	A	T	4: 139,301,855	V106D	probably damaging	Het
Prkx	A	G	X: 77,771,314	F247L	probably benign	Het
Qpct	G	A	17: 79,070,686	R95Q	probably benign	Het
Ralgapb	G	T	2: 158,437,472	M159I	probably benign	Het
Rnf145	T	C	11: 44,555,170	L277P	probably damaging	Het
Slc4a8	A	G	15: 100,806,373	T750A	probably damaging	Het
Syne2	A	G	12: 76,094,456	E6114G	probably damaging	Het
Tat	T	C	8: 109,997,604	M375T	probably damaging	Het
Tex10	C	T	4: 48,436,522		probably benign	Het
Tmprss11e	T	C	5: 86,713,728	K320E	probably benign	Het
Tnr	T	C	1: 159,858,270	I357T	probably damaging	Het
Vmn1r229	A	T	17: 20,815,376	R294S	possibly damaging	Het
Vmn2r116	G	A	17: 23,401,469	D726N	probably damaging	Het
Vpreb2	T	A	16: 17,981,070	L140*	probably null	Het
Wfs1	G	A	5: 36,967,942	P535L	probably damaging	Het
Xdh	A	G	17: 73,922,537	L307P	probably damaging	Het
Zfp160	A	G	17: 21,020,828	S53G	probably benign	Het
Zfp319	A	G	8: 95,328,031	C515R	probably damaging	Het
Zfp747	A	G	7: 127,375,757	F24L	possibly damaging	Het
Zzef1	A	T	11: 72,848,634		probably benign	Het

Other mutations in Scn9a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00514:Scn9a	APN	2	66563601	missense	probably damaging	1.00
IGL00570:Scn9a	APN	2	66484142	missense	probably damaging	1.00
IGL00809:Scn9a	APN	2	66483935	missense	probably damaging	1.00
IGL00977:Scn9a	APN	2	66484301	missense	probably damaging	0.99
IGL01120:Scn9a	APN	2	66526972	missense	probably benign	0.00
IGL01134:Scn9a	APN	2	66504968	missense	probably damaging	1.00
IGL01300:Scn9a	APN	2	66488053	nonsense	probably null
IGL01452:Scn9a	APN	2	66527072	missense	probably damaging	1.00
IGL01531:Scn9a	APN	2	66537378	missense	probably benign	0.11
IGL01572:Scn9a	APN	2	66493886	missense	probably benign	0.00
IGL01645:Scn9a	APN	2	66487642	missense	possibly damaging	0.62
IGL01823:Scn9a	APN	2	66484042	missense	probably damaging	1.00
IGL01965:Scn9a	APN	2	66484433	missense	probably damaging	1.00
IGL02127:Scn9a	APN	2	66547135	missense	probably damaging	1.00
IGL02127:Scn9a	APN	2	66494826	missense	probably damaging	1.00
IGL02166:Scn9a	APN	2	66493103	missense	possibly damaging	0.95
IGL02183:Scn9a	APN	2	66484611	splice site	probably benign
IGL02640:Scn9a	APN	2	66536096	critical splice donor site	probably null
IGL02685:Scn9a	APN	2	66537293	missense	probably damaging	1.00
IGL02798:Scn9a	APN	2	66540559	missense	possibly damaging	0.52
IGL02832:Scn9a	APN	2	66568029	missense	probably damaging	1.00
IGL03008:Scn9a	APN	2	66562511	missense	probably damaging	1.00
IGL03270:Scn9a	APN	2	66484014	missense	probably damaging	1.00
IGL03408:Scn9a	APN	2	66526747	missense	probably benign	0.00
R0039:Scn9a	UTSW	2	66562444	missense	probably damaging	0.98
R0173:Scn9a	UTSW	2	66533093	missense	probably damaging	1.00
R0323:Scn9a	UTSW	2	66568131	missense	probably damaging	1.00
R0344:Scn9a	UTSW	2	66505010	missense	probably damaging	0.99
R0421:Scn9a	UTSW	2	66543277	missense	probably benign
R0465:Scn9a	UTSW	2	66526996	missense	probably damaging	1.00
R0514:Scn9a	UTSW	2	66483678	missense	probably damaging	1.00
R0599:Scn9a	UTSW	2	66526799	missense	probably damaging	0.96
R0627:Scn9a	UTSW	2	66537377	missense	probably benign	0.00
R0644:Scn9a	UTSW	2	66533061	critical splice donor site	probably null
R0653:Scn9a	UTSW	2	66533377	missense	probably damaging	1.00
R0685:Scn9a	UTSW	2	66483499	missense	probably benign	0.02
R0718:Scn9a	UTSW	2	66547112	missense	probably damaging	1.00
R0827:Scn9a	UTSW	2	66536124	nonsense	probably null
R0890:Scn9a	UTSW	2	66483735	missense	probably damaging	1.00
R1139:Scn9a	UTSW	2	66504997	missense	probably benign	0.02
R1385:Scn9a	UTSW	2	66563542	missense	probably damaging	1.00
R1398:Scn9a	UTSW	2	66484586	missense	probably benign	0.11
R1496:Scn9a	UTSW	2	66526888	missense	probably benign
R1511:Scn9a	UTSW	2	66526813	missense	probably benign	0.01
R1517:Scn9a	UTSW	2	66505027	splice site	probably benign
R1564:Scn9a	UTSW	2	66484304	missense	probably damaging	1.00
R1634:Scn9a	UTSW	2	66488017	missense	probably damaging	1.00
R1662:Scn9a	UTSW	2	66483459	missense	probably benign	0.00
R1695:Scn9a	UTSW	2	66504876	nonsense	probably null
R1709:Scn9a	UTSW	2	66483506	missense	probably damaging	1.00
R1741:Scn9a	UTSW	2	66487594	missense	probably damaging	0.99
R1755:Scn9a	UTSW	2	66501716	missense	probably benign	0.38
R1914:Scn9a	UTSW	2	66566250	missense	probably damaging	1.00
R1962:Scn9a	UTSW	2	66484311	missense	probably damaging	1.00
R1970:Scn9a	UTSW	2	66515380	missense	probably damaging	0.97
R2017:Scn9a	UTSW	2	66515321	missense	probably damaging	0.99
R2092:Scn9a	UTSW	2	66533376	missense	probably damaging	0.99
R2105:Scn9a	UTSW	2	66568183	missense	probably benign	0.25
R2114:Scn9a	UTSW	2	66484052	missense	probably damaging	1.00
R2115:Scn9a	UTSW	2	66484052	missense	probably damaging	1.00
R2128:Scn9a	UTSW	2	66526654	missense	probably damaging	1.00
R2162:Scn9a	UTSW	2	66534229	missense	probably damaging	0.98
R2350:Scn9a	UTSW	2	66504968	missense	probably damaging	1.00
R3694:Scn9a	UTSW	2	66562405	missense	probably benign
R3771:Scn9a	UTSW	2	66483648	missense	probably benign	0.26
R3772:Scn9a	UTSW	2	66483648	missense	probably benign	0.26
R3773:Scn9a	UTSW	2	66483648	missense	probably benign	0.26
R3922:Scn9a	UTSW	2	66526873	missense	possibly damaging	0.88
R3926:Scn9a	UTSW	2	66526873	missense	possibly damaging	0.88
R4258:Scn9a	UTSW	2	66565054	intron	probably benign
R4385:Scn9a	UTSW	2	66484556	missense	probably damaging	1.00
R4415:Scn9a	UTSW	2	66526693	missense	probably damaging	1.00
R4570:Scn9a	UTSW	2	66483558	missense	possibly damaging	0.85
R4682:Scn9a	UTSW	2	66547018	missense	probably benign
R4783:Scn9a	UTSW	2	66540623	missense	probably benign	0.01
R4822:Scn9a	UTSW	2	66483749	missense	possibly damaging	0.55
R4829:Scn9a	UTSW	2	66551713	missense	probably benign
R4908:Scn9a	UTSW	2	66526743	missense	probably benign	0.03
R4983:Scn9a	UTSW	2	66566270	missense	probably benign	0.02
R5047:Scn9a	UTSW	2	66562480	missense	probably damaging	1.00
R5100:Scn9a	UTSW	2	66534119	missense	probably damaging	1.00
R5140:Scn9a	UTSW	2	66565167	missense	possibly damaging	0.81
R5398:Scn9a	UTSW	2	66488043	missense	probably damaging	1.00
R5557:Scn9a	UTSW	2	66547103	missense	probably damaging	0.99
R5582:Scn9a	UTSW	2	66565029	intron	probably benign
R6108:Scn9a	UTSW	2	66484049	missense	probably damaging	1.00
R6115:Scn9a	UTSW	2	66563629	missense	possibly damaging	0.70
R6143:Scn9a	UTSW	2	66487524	missense	probably benign	0.00
R6261:Scn9a	UTSW	2	66483896	missense	probably damaging	1.00
R6335:Scn9a	UTSW	2	66568264	start codon destroyed	possibly damaging	0.91
R6429:Scn9a	UTSW	2	66526963	missense	possibly damaging	0.95
R6632:Scn9a	UTSW	2	66483502	missense	probably benign	0.23
R6681:Scn9a	UTSW	2	66563342	missense	possibly damaging	0.90
R6830:Scn9a	UTSW	2	66568029	missense	probably damaging	1.00
R7102:Scn9a	UTSW	2	66549015	missense	probably damaging	1.00
R7186:Scn9a	UTSW	2	66534223	missense	probably damaging	1.00
R7243:Scn9a	UTSW	2	66540530	missense	probably damaging	1.00
R7311:Scn9a	UTSW	2	66484404	missense	possibly damaging	0.54
R7328:Scn9a	UTSW	2	66484587	missense	probably benign
R7386:Scn9a	UTSW	2	66540550	missense	probably damaging	1.00
R7438:Scn9a	UTSW	2	66547187	missense	possibly damaging	0.81
R7483:Scn9a	UTSW	2	66533348	missense	probably damaging	0.99
R7485:Scn9a	UTSW	2	66534217	missense	probably damaging	1.00
R7526:Scn9a	UTSW	2	66483646	missense	probably benign
R7617:Scn9a	UTSW	2	66540549	missense	possibly damaging	0.55
R7642:Scn9a	UTSW	2	66536236	missense	probably benign	0.02
R7653:Scn9a	UTSW	2	66527080	missense	probably damaging	1.00
R7747:Scn9a	UTSW	2	66484298	missense	probably damaging	1.00
R7823:Scn9a	UTSW	2	66483791	missense	probably damaging	1.00
X0003:Scn9a	UTSW	2	66508647	missense	probably benign	0.02
X0062:Scn9a	UTSW	2	66568077	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TAGACAACTCACCAGGTTCCCG -3'
(R):5'- ATCTGCTGAGCTTCCAAAGAAAG -3'

Sequencing Primer
(F):5'- AGGTTCCCGACTGCAAGTAC -3'
(R):5'- CTGCTGAGCTTCCAAAGAAAGAGTAC -3'

Posted On

2014-10-01