Mutagenetix > Incidental Mutation

Incidental Mutation 'R1946:Kcnq2'

216653

Institutional Source

Beutler Lab

Gene Symbol

Kcnq2

Ensembl Gene

ENSMUSG00000016346

Gene Name

potassium voltage-gated channel, subfamily Q, member 2

Synonyms

KQT2, Nmf134

MMRRC Submission

039964-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1946 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

181075579-181135300 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 181088451 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 446 (D446V)

Ref Sequence

ENSEMBL: ENSMUSP00000052453 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000016491] [ENSMUST00000049792] [ENSMUST00000081528] [ENSMUST00000103047] [ENSMUST00000103048] [ENSMUST00000103050] [ENSMUST00000103051] [ENSMUST00000129695] [ENSMUST00000149964] [ENSMUST00000197015]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000016491
AA Change: D446V

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000016491
Gene: ENSMUSG00000016346
AA Change: D446V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	7.3e-29	PFAM
Pfam:Ion_trans_2	237	317	2.5e-14	PFAM
Pfam:KCNQ_channel	436	595	2e-59	PFAM
Pfam:KCNQ_channel	593	673	1.7e-22	PFAM
low complexity region	711	723	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000049792
AA Change: D446V

PolyPhen 2 Score 0.085 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000052453
Gene: ENSMUSG00000016346
AA Change: D446V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	7.2e-29	PFAM
Pfam:Ion_trans_2	237	317	2.5e-14	PFAM
Pfam:KCNQ_channel	436	565	3.1e-55	PFAM
Pfam:KCNQ_channel	587	668	6.8e-23	PFAM
low complexity region	706	718	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000081528
AA Change: D446V

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000080243
Gene: ENSMUSG00000016346
AA Change: D446V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	4.3e-29	PFAM
Pfam:Ion_trans_2	237	317	1.7e-14	PFAM
Pfam:KCNQ_channel	436	564	2.3e-55	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000103047
AA Change: D434V

PolyPhen 2 Score 0.065 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000099336
Gene: ENSMUSG00000016346
AA Change: D434V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	7.1e-29	PFAM
Pfam:Ion_trans_2	237	317	2.5e-14	PFAM
Pfam:KCNQ_channel	424	583	2e-59	PFAM
Pfam:KCNQ_channel	581	661	1.7e-22	PFAM
low complexity region	699	711	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000103048
AA Change: D446V

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000099337
Gene: ENSMUSG00000016346
AA Change: D446V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	6.7e-29	PFAM
Pfam:Ion_trans_2	237	317	2.4e-14	PFAM
Pfam:KCNQ_channel	436	637	1.3e-82	PFAM
low complexity region	675	687	N/A	INTRINSIC

Predicted Effect

unknown
Transcript: ENSMUST00000103049
AA Change: D399V

SMART Domains

Protein: ENSMUSP00000099338
Gene: ENSMUSG00000016346
AA Change: D399V

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	35	268	3.7e-32	PFAM
Pfam:Ion_trans_2	181	261	1.1e-14	PFAM
Pfam:KCNQ_channel	392	584	1e-92	PFAM
Pfam:KCNQ2_u3	591	679	3.9e-39	PFAM
Pfam:KCNQC3-Ank-G_bd	692	791	1.1e-48	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000103050
AA Change: D444V

SMART Domains

Protein: ENSMUSP00000099339
Gene: ENSMUSG00000016346
AA Change: D444V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	8.7e-29	PFAM
Pfam:Ion_trans_2	237	317	2.9e-14	PFAM
Pfam:KCNQ_channel	436	637	1.7e-82	PFAM
low complexity region	675	687	N/A	INTRINSIC
Pfam:KCNQC3-Ank-G_bd	737	839	1.6e-51	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000103051
AA Change: D456V

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000099340
Gene: ENSMUSG00000016346
AA Change: D456V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	8.9e-29	PFAM
Pfam:Ion_trans_2	237	317	2.9e-14	PFAM
Pfam:KCNQ_channel	446	647	1.7e-82	PFAM
low complexity region	685	697	N/A	INTRINSIC
Pfam:KCNQC3-Ank-G_bd	747	849	1.7e-51	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129073

SMART Domains

Protein: ENSMUSP00000127061
Gene: ENSMUSG00000016346

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	1e-28	PFAM
Pfam:Ion_trans_2	237	317	3.4e-14	PFAM
Pfam:KCNQ_channel	436	565	3e-55	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000129695
AA Change: D330V

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000123488
Gene: ENSMUSG00000016346
AA Change: D330V

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	14	198	6.8e-29	PFAM
Pfam:Ion_trans_2	123	203	2.4e-14	PFAM
Pfam:KCNQ_channel	320	521	1.3e-82	PFAM
low complexity region	559	571	N/A	INTRINSIC
Pfam:KCNQC3-Ank-G_bd	621	723	1.3e-51	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000149964
AA Change: D474V

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000122915
Gene: ENSMUSG00000016346
AA Change: D474V

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	91	324	4.4e-32	PFAM
Pfam:Ion_trans_2	237	317	1.3e-14	PFAM
low complexity region	418	431	N/A	INTRINSIC
Pfam:KCNQ_channel	466	659	6.2e-94	PFAM
Pfam:KCNQ2_u3	666	754	4.5e-39	PFAM
Pfam:KCNQC3-Ank-G_bd	767	866	1.2e-48	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000197015
AA Change: D446V

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000143263
Gene: ENSMUSG00000016346
AA Change: D446V

Domain	Start	End	E-Value	Type
transmembrane domain	93	115	N/A	INTRINSIC
Pfam:Ion_trans	128	312	8.7e-29	PFAM
Pfam:Ion_trans_2	237	317	2.9e-14	PFAM
Pfam:KCNQ_channel	436	637	1.7e-82	PFAM
low complexity region	675	687	N/A	INTRINSIC
Pfam:KCNQC3-Ank-G_bd	737	839	1.6e-51	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000197599
AA Change: D152V

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000152099

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145861

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.8%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null mutation die perinatally with pulmonary atelectasis. Heterozygous mice exhibit a hypersensitivity to the epileptic inducer pentylenetetrazole. Mice homozygous for a knock-in allele exhibit spontaneous seizures and premature death. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aasdh	A	G	5: 76,891,704	S253P	probably damaging	Het
Adamts5	C	A	16: 85,899,243	C342F	probably damaging	Het
Adgrv1	C	T	13: 81,374,249	C5923Y	probably damaging	Het
Aen	G	C	7: 78,902,672	E32Q	probably damaging	Het
Apba2	T	C	7: 64,744,630		probably null	Het
Arhgap44	A	G	11: 65,012,096	M509T	probably damaging	Het
Arpc1b	A	G	5: 145,122,633	T56A	probably null	Het
Atoh1	T	C	6: 64,729,459	V46A	probably benign	Het
Bmpr2	T	C	1: 59,868,397	V883A	possibly damaging	Het
Bpifa1	A	T	2: 154,145,634	I135F	probably damaging	Het
Bsn	A	G	9: 108,114,651	F1301L	probably damaging	Het
Capn13	T	C	17: 73,350,525	E240G	possibly damaging	Het
Ccdc18	A	G	5: 108,228,995	E1434G	probably damaging	Het
Coq8b	G	A	7: 27,239,874	V150I	possibly damaging	Het
Cpn1	G	A	19: 43,956,518	T450M	probably benign	Het
Dlg4	A	G	11: 70,039,575	Y432C	probably damaging	Het
Dnah8	C	A	17: 30,712,385	T1458K	probably benign	Het
Dock5	A	T	14: 67,786,316	M1132K	probably damaging	Het
Dsg2	A	G	18: 20,580,548	D192G	probably damaging	Het
F930017D23Rik	G	A	10: 43,593,444		noncoding transcript	Het
Fndc11	A	T	2: 181,221,834	D144V	probably benign	Het
Fut2	A	G	7: 45,651,324	F8S	probably damaging	Het
Gad2	A	T	2: 22,685,428	T515S	probably benign	Het
Ganab	T	A	19: 8,910,808	D439E	probably damaging	Het
Gm10228	C	A	16: 89,041,353	G21V	unknown	Het
Gm13119	T	A	4: 144,361,865	V77E	probably benign	Het
Gm9573	A	T	17: 35,622,524		probably benign	Het
Grm3	A	G	5: 9,512,123	W576R	probably damaging	Het
Gsdmc4	C	A	15: 63,902,780	D51Y	probably benign	Het
Hmcn2	T	C	2: 31,405,635	S2619P	probably damaging	Het
Kera	A	G	10: 97,609,147	K123E	probably benign	Het
Kmt2c	A	T	5: 25,315,154	V1986E	probably benign	Het
Lrp11	T	C	10: 7,623,776	Y244H	probably damaging	Het
Lrp1b	T	A	2: 40,665,147	D320V	unknown	Het
Lrrcc1	A	G	3: 14,550,393	R394G	probably benign	Het
Lrrk2	G	A	15: 91,736,661		probably null	Het
Map4k5	A	T	12: 69,845,755	D133E	probably damaging	Het
Megf11	A	T	9: 64,679,276	D461V	probably damaging	Het
Msrb3	A	G	10: 120,852,008	V54A	probably damaging	Het
Ncoa3	T	A	2: 166,059,177	N896K	possibly damaging	Het
Ncor2	G	A	5: 125,034,412	T1314I	probably damaging	Het
Nes	A	G	3: 87,978,514	Q1316R	possibly damaging	Het
Nfe2l3	A	C	6: 51,457,315	Q285P	probably damaging	Het
Nkd1	C	T	8: 88,592,117	H357Y	probably damaging	Het
Nmt2	T	A	2: 3,322,635	I355N	probably benign	Het
Olfr1333	T	C	4: 118,830,026	N139S	probably benign	Het
Olfr1354	T	A	10: 78,916,924	I28N	probably damaging	Het
Olfr1469	T	C	19: 13,410,779	V70A	possibly damaging	Het
Olfr147	T	A	9: 38,402,886	M1K	probably null	Het
Olfr290	T	C	7: 84,916,279	S167P	probably benign	Het
Olfr353	A	T	2: 36,890,446	M134K	possibly damaging	Het
Otx1	G	T	11: 21,998,482	T46K	probably damaging	Het
Panx1	A	G	9: 15,007,526	C346R	probably benign	Het
Pcdhb16	T	A	18: 37,478,899	L304*	probably null	Het
Plet1	A	G	9: 50,504,352		probably null	Het
Plod2	A	G	9: 92,607,135	S707G	probably damaging	Het
Plscr4	G	A	9: 92,483,836	V120I	probably damaging	Het
Ppp1r12b	A	G	1: 134,892,270	V245A	probably damaging	Het
Ppp2r2d	A	G	7: 138,868,467	D19G	probably damaging	Het
Rimbp3	G	A	16: 17,210,427	V572I	probably benign	Het
Ror2	T	C	13: 53,131,849	I110V	probably damaging	Het
Sec24d	A	T	3: 123,353,394	H667L	probably benign	Het
Sema3d	A	G	5: 12,573,843	Q573R	probably damaging	Het
Snx19	T	A	9: 30,432,324	N593K	probably damaging	Het
Sulf1	T	C	1: 12,796,907	V105A	probably benign	Het
Syngr3	T	C	17: 24,687,706	N45S	probably benign	Het
Tenm4	A	T	7: 96,735,808	H524L	probably damaging	Het
Tex30	C	T	1: 44,091,404	G68D	probably damaging	Het
Tmem43	A	T	6: 91,486,909	I389F	probably benign	Het
Trpm1	A	T	7: 64,223,808	N488Y	probably damaging	Het
Usf2	T	C	7: 30,956,238	T1A	probably null	Het
Vill	A	T	9: 119,058,492	H108L	probably benign	Het
Vmn1r16	T	C	6: 57,322,900	I246V	probably benign	Het
Vmn1r188	T	G	13: 22,088,645	S256R	possibly damaging	Het
Zfp12	G	A	5: 143,245,378	E487K	probably damaging	Het
Zfp24	AC	A	18: 24,014,419		probably null	Het

Other mutations in Kcnq2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01063:Kcnq2	APN	2	181109789	unclassified	probably benign
IGL02064:Kcnq2	APN	2	181109026	missense	probably damaging	1.00
IGL02231:Kcnq2	APN	2	181081715	missense	probably benign	0.22
IGL02261:Kcnq2	APN	2	181081690	missense	probably damaging	0.98
IGL02510:Kcnq2	APN	2	181081361	missense	probably benign
IGL02583:Kcnq2	APN	2	181081502	missense	probably benign	0.01
IGL02627:Kcnq2	APN	2	181082327	unclassified	probably benign
IGL03303:Kcnq2	APN	2	181082389	missense	probably benign
R0269:Kcnq2	UTSW	2	181096974	missense	probably benign	0.00
R1535:Kcnq2	UTSW	2	181134825	missense	probably damaging	1.00
R1688:Kcnq2	UTSW	2	181087033	missense	probably damaging	1.00
R1776:Kcnq2	UTSW	2	181100557	missense	probably benign	0.01
R2105:Kcnq2	UTSW	2	181081352	missense	probably benign	0.03
R2382:Kcnq2	UTSW	2	181112107	missense	probably damaging	1.00
R2912:Kcnq2	UTSW	2	181081774	missense	probably damaging	1.00
R3826:Kcnq2	UTSW	2	181104900	missense	possibly damaging	0.56
R3898:Kcnq2	UTSW	2	181109686	missense	probably damaging	0.97
R4282:Kcnq2	UTSW	2	181081153	missense	probably damaging	1.00
R4938:Kcnq2	UTSW	2	181086973	missense	probably damaging	0.96
R4962:Kcnq2	UTSW	2	181112043	missense	possibly damaging	0.59
R5055:Kcnq2	UTSW	2	181086761	intron	probably benign
R5107:Kcnq2	UTSW	2	181108547	intron	probably benign
R5371:Kcnq2	UTSW	2	181135020	missense	probably damaging	1.00
R5557:Kcnq2	UTSW	2	181134897	missense	probably benign	0.07
R5839:Kcnq2	UTSW	2	181109751	missense	probably damaging	1.00
R5998:Kcnq2	UTSW	2	181087008	missense	probably damaging	1.00
R6084:Kcnq2	UTSW	2	181087656	missense	possibly damaging	0.53
R6207:Kcnq2	UTSW	2	181113233	missense	possibly damaging	0.49
R6744:Kcnq2	UTSW	2	181085306	missense	possibly damaging	0.94
R7018:Kcnq2	UTSW	2	181081724	nonsense	probably null
R7266:Kcnq2	UTSW	2	181135092	start codon destroyed	probably null	0.92
R7291:Kcnq2	UTSW	2	181088379	missense	possibly damaging	0.69
R7319:Kcnq2	UTSW	2	181109102	missense	probably damaging	1.00
R7447:Kcnq2	UTSW	2	181113094	missense	probably damaging	0.97
R7573:Kcnq2	UTSW	2	181081589	missense	probably benign	0.04
R7897:Kcnq2	UTSW	2	181081141	missense	probably damaging	1.00
R8942:Kcnq2	UTSW	2	181082451	missense	probably damaging	1.00
R9381:Kcnq2	UTSW	2	181109769	missense	probably damaging	0.97
R9394:Kcnq2	UTSW	2	181082424	missense	probably benign
R9516:Kcnq2	UTSW	2	181134960	missense	probably benign	0.00
R9544:Kcnq2	UTSW	2	181087614	missense	probably damaging	1.00
R9592:Kcnq2	UTSW	2	181087020	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGCCAAGTATTGATGTCCTTCCC -3'
(R):5'- CAAAGAGACTTGTGAACGTGAC -3'

Sequencing Primer
(F):5'- AAGTATTGATGTCCTTCCCCCATCAG -3'
(R):5'- GAACGTGACTTTGTTATTTCCAGAG -3'

Posted On

2014-08-01