Mutagenetix > Incidental Mutations

Incidental Mutation 'R7291:Kcnq2'

566390

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

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R7291 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

181075579-181135300 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 181088379 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 498 (I498N)

Ref Sequence

ENSEMBL: ENSMUSP00000122915 (fasta)

Gene Model

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000016491
AA Change: I470N

PolyPhen 2 Score 0.792 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000016491
Gene: ENSMUSG00000016346
AA Change: I470N

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

possibly damaging
Transcript: ENSMUST00000049792
AA Change: I470N

PolyPhen 2 Score 0.792 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000052453
Gene: ENSMUSG00000016346
AA Change: I470N

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

possibly damaging
Transcript: ENSMUST00000081528
AA Change: I470N

PolyPhen 2 Score 0.869 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000080243
Gene: ENSMUSG00000016346
AA Change: I470N

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: I458N

PolyPhen 2 Score 0.191 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000099336
Gene: ENSMUSG00000016346
AA Change: I458N

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

possibly damaging
Transcript: ENSMUST00000103048
AA Change: I470N

PolyPhen 2 Score 0.670 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000099337
Gene: ENSMUSG00000016346
AA Change: I470N

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

SMART Domains

Protein: ENSMUSP00000099338
Gene: ENSMUSG00000016346
AA Change: I423N

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

SMART Domains

Protein: ENSMUSP00000099339
Gene: ENSMUSG00000016346
AA Change: I468N

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

possibly damaging
Transcript: ENSMUST00000103051
AA Change: I480N

PolyPhen 2 Score 0.522 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000099340
Gene: ENSMUSG00000016346
AA Change: I480N

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

probably benign
Transcript: ENSMUST00000129695
AA Change: I354N

PolyPhen 2 Score 0.032 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000123488
Gene: ENSMUSG00000016346
AA Change: I354N

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

possibly damaging
Transcript: ENSMUST00000149964
AA Change: I498N

PolyPhen 2 Score 0.686 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000122915
Gene: ENSMUSG00000016346
AA Change: I498N

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

possibly damaging
Transcript: ENSMUST00000197015
AA Change: I470N

PolyPhen 2 Score 0.792 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000143263
Gene: ENSMUSG00000016346
AA Change: I470N

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9430069I07Rik	T	C	15: 34,355,553	E51G	possibly damaging	Het
9530053A07Rik	A	C	7: 28,140,220	D486A	probably benign	Het
Abca14	C	A	7: 120,289,609	C1259*	probably null	Het
Ablim1	T	C	19: 57,215,908	E17G	probably benign	Het
Acsf3	G	A	8: 122,813,577	V505I	probably benign	Het
Actn1	T	C	12: 80,174,085	M650V	probably benign	Het
Adamts4	G	A	1: 171,256,528	V525I	probably benign	Het
Adh1	T	C	3: 138,282,808	Y181H	probably damaging	Het
Alpl	G	A	4: 137,752,698	R168W	probably damaging	Het
Ate1	T	G	7: 130,519,931	K11Q	probably benign	Het
Atpaf1	T	A	4: 115,811,091	F314L	probably damaging	Het
Baiap3	T	A	17: 25,244,317	D1004V	probably damaging	Het
Bpifb9a	C	T	2: 154,267,696	T504M	probably damaging	Het
C1s2	T	A	6: 124,625,384	I623F	probably benign	Het
Card11	T	C	5: 140,901,070	D308G	probably damaging	Het
Cul9	C	T	17: 46,540,433	V354I	probably benign	Het
Dnah1	A	T	14: 31,298,705	F1236I	probably damaging	Het
Dync2h1	T	A	9: 6,929,590	I4266F	possibly damaging	Het
Ear10	A	T	14: 43,922,920	V150D	probably damaging	Het
Elfn2	C	T	15: 78,672,983	A455T	probably benign	Het
Erp44	A	G	4: 48,208,792	Y223H	probably damaging	Het
Fam110b	T	A	4: 5,798,895	H104Q	probably benign	Het
Fcgbp	A	G	7: 28,101,392	N1288D	probably benign	Het
Fcrl1	T	C	3: 87,385,781		probably null	Het
Fmo2	G	T	1: 162,887,702	P117Q	probably benign	Het
Fsip2	A	G	2: 82,980,519	K2394R	possibly damaging	Het
Gab1	T	G	8: 80,800,151	K106T	probably damaging	Het
Gatad2b	T	C	3: 90,351,414	V248A	probably damaging	Het
Gemin6	T	C	17: 80,227,775	S55P	possibly damaging	Het
Gfm2	G	A	13: 97,175,024	V701I	probably benign	Het
Gm3250	T	C	10: 77,782,227	T106A	unknown	Het
Gm7356	T	C	17: 14,001,581	N62S	probably benign	Het
Gsdmc4	T	C	15: 63,902,840	T31A	possibly damaging	Het
H2-M10.1	T	A	17: 36,325,729	D61V	probably damaging	Het
Heatr5a	A	G	12: 51,925,339	L716S	probably damaging	Het
Hecw2	A	G	1: 53,914,594	Y831H	probably damaging	Het
Ifi202b	C	T	1: 173,974,815	S151N	probably benign	Het
Il15ra	C	T	2: 11,718,381	T72I	probably damaging	Het
Ints1	A	G	5: 139,765,074	L858P	probably damaging	Het
Kat2a	C	T	11: 100,710,900	V230I	possibly damaging	Het
Kif26b	C	T	1: 178,679,046	T229I	possibly damaging	Het
Ly75	T	A	2: 60,329,993	I957F	probably damaging	Het
Map3k12	T	A	15: 102,502,166	R459W	probably damaging	Het
Mia2	T	A	12: 59,158,369		probably null	Het
Mrgprf	A	G	7: 145,307,469	I53V	unknown	Het
Mttp	A	G	3: 138,091,203	L846P	probably damaging	Het
Myrip	C	T	9: 120,417,141	L112F	probably damaging	Het
Nav1	A	G	1: 135,465,859	F1047S	probably damaging	Het
Nfkbib	T	C	7: 28,759,203	D327G	possibly damaging	Het
Notch1	C	T	2: 26,476,375	V776I	probably benign	Het
Obsl1	G	T	1: 75,489,517	D1522E	probably damaging	Het
Olfr1464-ps1	A	T	19: 13,282,153	F302I	unknown	Het
Olfr605	T	A	7: 103,442,788	M112L	probably benign	Het
Olfr823	T	C	10: 130,112,224	K189E	probably benign	Het
Olfr859	T	C	9: 19,808,648	M110T	possibly damaging	Het
Pde7a	T	C	3: 19,227,674	N471D	probably benign	Het
Pla2r1	T	C	2: 60,530,435	H203R	probably benign	Het
Plch2	C	A	4: 154,998,472	C573F	probably damaging	Het
Polr1a	G	A	6: 71,941,456	R666Q	probably benign	Het
Prepl	T	C	17: 85,081,240	N145S	probably benign	Het
Psen2	C	T	1: 180,238,956	V139M	probably benign	Het
Ptgdr	A	T	14: 44,859,192	M21K	possibly damaging	Het
Rapgef6	T	C	11: 54,691,239	W1331R	probably benign	Het
Rp1l1	G	A	14: 64,032,298	G1778S	probably benign	Het
Rrbp1	A	T	2: 143,969,462	M824K	probably benign	Het
Sel1l	T	C	12: 91,848,965	T23A	probably benign	Het
Sele	A	G	1: 164,053,868	S515G	possibly damaging	Het
Slc22a23	T	C	13: 34,197,839	N421D	probably damaging	Het
Slc35f3	T	G	8: 126,394,558	L386R	probably benign	Het
Stab2	G	A	10: 86,946,220	S699L	probably damaging	Het
Synrg	A	T	11: 84,009,381	L726F	probably damaging	Het
Syt3	G	A	7: 44,395,919	V528M	probably damaging	Het
Szt2	A	G	4: 118,391,249	I655T	probably damaging	Het
Tbr1	T	C	2: 61,812,256	S622P	probably damaging	Het
Tex36	C	T	7: 133,587,223	G207S	probably benign	Het
Trav5n-4	G	A	14: 53,312,942	W13*	probably null	Het
Trdn	A	T	10: 33,437,736	E500V	probably null	Het
Ugt2b38	A	T	5: 87,411,895	N379K	probably damaging	Het
Unc13d	T	C	11: 116,074,050	R248G	possibly damaging	Het
Vmn1r195	C	T	13: 22,278,749	L130F	probably damaging	Het
Vmn2r110	T	C	17: 20,574,209	I733V	probably benign	Het
Zfp870	T	A	17: 32,883,854	N167I	probably damaging	Het
Zmynd10	A	T	9: 107,549,304	M179L	probably benign	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
R1946:Kcnq2	UTSW	2	181088451	missense	probably benign	0.09
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
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

Predicted Primers

PCR Primer
(F):5'- CCATTACCTGCAGAGATGGCAAG -3'
(R):5'- AAGATCGTGTCTTCTCCAGCC -3'

Sequencing Primer
(F):5'- GTGGTTTGTCTTACATGACATCAC -3'
(R):5'- GTCTTCTCCAGCCCCCGAG -3'

Posted On

2019-06-26