Mutagenetix > Incidental Mutation

Incidental Mutation 'R9381:Kcnq2'

709993

Institutional Source

Beutler Lab

Gene Symbol

Kcnq2

Ensembl Gene

ENSMUSG00000016346

Gene Name

potassium voltage-gated channel, subfamily Q, member 2

Synonyms

Nmf134, KQT2

MMRRC Submission

068992-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9381 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

180717372-180777093 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 180751562 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 278 (I278T)

Ref Sequence

ENSEMBL: ENSMUSP00000122915 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000016491
AA Change: I278T

PolyPhen 2 Score 0.945 (Sensitivity: 0.80; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000016491
Gene: ENSMUSG00000016346
AA Change: I278T

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 damaging
Transcript: ENSMUST00000049792
AA Change: I278T

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000052453
Gene: ENSMUSG00000016346
AA Change: I278T

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 damaging
Transcript: ENSMUST00000081528
AA Change: I278T

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000080243
Gene: ENSMUSG00000016346
AA Change: I278T

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 damaging
Transcript: ENSMUST00000103047
AA Change: I278T

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000099336
Gene: ENSMUSG00000016346
AA Change: I278T

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: I278T

PolyPhen 2 Score 0.903 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000099337
Gene: ENSMUSG00000016346
AA Change: I278T

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

probably damaging
Transcript: ENSMUST00000103049
AA Change: I221T

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000099338
Gene: ENSMUSG00000016346
AA Change: I221T

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: I278T

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 damaging
Transcript: ENSMUST00000149964
AA Change: I278T

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000122915
Gene: ENSMUSG00000016346
AA Change: I278T

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: ENSMUST00000103051
AA Change: I278T

PolyPhen 2 Score 0.903 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000099340
Gene: ENSMUSG00000016346
AA Change: I278T

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

possibly damaging
Transcript: ENSMUST00000129695
AA Change: I164T

PolyPhen 2 Score 0.659 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000123488
Gene: ENSMUSG00000016346
AA Change: I164T

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 damaging
Transcript: ENSMUST00000197015
AA Change: I278T

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

SMART Domains

Protein: ENSMUSP00000143263
Gene: ENSMUSG00000016346
AA Change: I278T

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: ENSMUST00000197599

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2200002D01Rik	CCTTCTCCTTCTTCTCCTTCTTCTCCTTCTTCTCCATCTTCTCCTTCTTC	CCTTCTCCTTCTTCTCCTTCTTCTCCATCTTCTCCTTCTTC	7: 28,947,048 (GRCm39)		probably benign	Het
9930111J21Rik1	T	A	11: 48,839,204 (GRCm39)	K461M	probably damaging	Het
Abhd16b	A	G	2: 181,135,881 (GRCm39)	Y261C	probably damaging	Het
Acadl	T	C	1: 66,893,805 (GRCm39)	T117A	probably benign	Het
Adamts15	A	G	9: 30,813,816 (GRCm39)	V783A	probably damaging	Het
Aff1	A	T	5: 103,981,733 (GRCm39)	Q624L	possibly damaging	Het
Afg3l2	T	G	18: 67,575,451 (GRCm39)	E74A	probably damaging	Het
Aig1	T	C	10: 13,523,417 (GRCm39)	E238G	probably benign	Het
Ankrd17	C	T	5: 90,416,508 (GRCm39)	R1108Q	probably damaging	Het
Anks1	A	T	17: 28,272,979 (GRCm39)	Y958F	probably damaging	Het
Arhgef28	C	A	13: 98,036,269 (GRCm39)	Q1663H	possibly damaging	Het
Asb3	T	C	11: 31,051,088 (GRCm39)	L475P	probably damaging	Het
Atg9a	T	A	1: 75,162,726 (GRCm39)	M430L	probably benign	Het
Bco1	T	A	8: 117,837,631 (GRCm39)	V164E	probably benign	Het
Bhlhe40	T	C	6: 108,642,244 (GRCm39)	L396P	probably damaging	Het
C5ar2	A	T	7: 15,970,887 (GRCm39)	S347T	probably damaging	Het
Cdc42bpa	T	C	1: 179,969,048 (GRCm39)	S1212P	probably damaging	Het
Ceacam3	C	G	7: 16,893,715 (GRCm39)	Q409E		Het
Ces3b	T	C	8: 105,811,670 (GRCm39)	V62A	probably benign	Het
Dalrd3	A	G	9: 108,448,242 (GRCm39)		probably null	Het
Ddhd2	G	T	8: 26,239,849 (GRCm39)	A288E	probably benign	Het
Dnah17	T	A	11: 117,914,219 (GRCm39)	M4435L	probably benign	Het
Dok1	T	C	6: 83,009,972 (GRCm39)	K46E	probably damaging	Het
E030025P04Rik	A	G	11: 109,030,384 (GRCm39)	Y168H	unknown	Het
Elavl2	T	C	4: 91,197,009 (GRCm39)	N23S	probably benign	Het
Elfn1	T	C	5: 139,959,462 (GRCm39)	V822A	probably damaging	Het
Emb	G	T	13: 117,357,096 (GRCm39)		probably benign	Het
Exoc5	C	T	14: 49,275,194 (GRCm39)	S202N	probably benign	Het
Fryl	T	C	5: 73,240,637 (GRCm39)	D1321G	probably benign	Het
Gm12258	C	T	11: 58,750,007 (GRCm39)	T394I	unknown	Het
Gm28363	T	A	1: 117,654,615 (GRCm39)	S85T	probably damaging	Het
H2-Q1	A	G	17: 35,542,138 (GRCm39)	T237A	probably damaging	Het
Hectd4	A	T	5: 121,472,492 (GRCm39)	I2743F	possibly damaging	Het
Hs3st3b1	C	T	11: 63,812,692 (GRCm39)	G8S	probably benign	Het
Ighv1-16	T	C	12: 114,629,598 (GRCm39)	N63S	probably benign	Het
Il20rb	A	G	9: 100,343,541 (GRCm39)	F238L	possibly damaging	Het
Il31ra	A	T	13: 112,668,253 (GRCm39)	F439I	possibly damaging	Het
Jup	C	T	11: 100,270,391 (GRCm39)	C372Y	probably damaging	Het
Kat2a	T	C	11: 100,602,692 (GRCm39)	Q132R	possibly damaging	Het
Lama1	T	C	17: 68,044,479 (GRCm39)	V126A		Het
Lama2	T	A	10: 27,064,023 (GRCm39)	R1285*	probably null	Het
Larp1	A	G	11: 57,949,532 (GRCm39)	T1054A	probably benign	Het
Lrp1	A	T	10: 127,441,337 (GRCm39)	M262K	probably benign	Het
Lrrd1	A	G	5: 3,901,074 (GRCm39)	I460V	probably benign	Het
Ltbp1	A	T	17: 75,696,434 (GRCm39)	N1606I	probably damaging	Het
Mdga2	T	C	12: 66,597,304 (GRCm39)	N730S	possibly damaging	Het
Mpzl1	T	C	1: 165,429,323 (GRCm39)	H236R	probably damaging	Het
Mrps31	G	A	8: 22,904,752 (GRCm39)	R47K	probably damaging	Het
Nae1	A	T	8: 105,250,239 (GRCm39)	I218K	probably benign	Het
Npy2r	T	C	3: 82,448,356 (GRCm39)	T140A	probably damaging	Het
Nr2e1	T	A	10: 42,439,468 (GRCm39)	L350F	probably damaging	Het
Nup210l	C	T	3: 90,107,173 (GRCm39)	P1570L	probably benign	Het
Or51d1	A	T	7: 102,347,654 (GRCm39)	M70L	probably damaging	Het
Or5b124	G	T	19: 13,610,647 (GRCm39)	M57I	probably damaging	Het
Or5p50	A	C	7: 107,421,812 (GRCm39)	L288W	probably damaging	Het
Pabpc1l	G	T	2: 163,867,423 (GRCm39)	C8F	probably benign	Het
Pafah1b3	A	C	7: 24,994,699 (GRCm39)	F172V	probably benign	Het
Pcdhga6	A	T	18: 37,841,371 (GRCm39)	T364S	probably damaging	Het
Ppp3cc	T	A	14: 70,462,441 (GRCm39)	M399L	probably benign	Het
Prpsap2	T	C	11: 61,635,782 (GRCm39)	I173V	probably benign	Het
Rabggtb	A	T	3: 153,613,817 (GRCm39)	W252R	probably damaging	Het
Raph1	A	G	1: 60,540,959 (GRCm39)	F351L	unknown	Het
Rasd2	T	C	8: 75,948,589 (GRCm39)	S172P	probably damaging	Het
Rbm15	T	C	3: 107,238,752 (GRCm39)	T549A	probably benign	Het
Reln	A	G	5: 22,549,202 (GRCm39)	Y69H	possibly damaging	Het
Samd3	T	A	10: 26,147,643 (GRCm39)	N439K	probably benign	Het
Scap	C	A	9: 110,207,839 (GRCm39)	A516D	probably damaging	Het
Selplg	T	C	5: 113,957,917 (GRCm39)	T130A	probably benign	Het
Slc12a7	A	G	13: 73,949,063 (GRCm39)	M697V	probably benign	Het
Slc22a29	A	G	19: 8,195,841 (GRCm39)	I66T	probably benign	Het
Slco1a7	T	C	6: 141,711,490 (GRCm39)	I74V	probably benign	Het
Snrnp48	A	C	13: 38,404,667 (GRCm39)	I241L	probably damaging	Het
Sptb	C	T	12: 76,634,292 (GRCm39)	E2140K	probably benign	Het
Strip2	T	C	6: 29,927,333 (GRCm39)	S192P	probably benign	Het
Svil	A	T	18: 5,099,013 (GRCm39)	R1643S	probably benign	Het
Tbc1d2b	A	G	9: 90,101,139 (GRCm39)	V617A	possibly damaging	Het
Tmem102	T	C	11: 69,695,141 (GRCm39)	E277G	probably benign	Het
Tmtc4	T	G	14: 123,163,441 (GRCm39)	I648L	probably benign	Het
Togaram1	T	C	12: 65,014,204 (GRCm39)	V485A	probably damaging	Het
Trim43b	T	C	9: 88,969,642 (GRCm39)	I269V	probably benign	Het
Trpm2	T	A	10: 77,747,191 (GRCm39)	I1436F	possibly damaging	Het
Ube2d3	A	T	3: 135,168,722 (GRCm39)	I106F	possibly damaging	Het
Vdr	G	A	15: 97,755,333 (GRCm39)	R397C	probably damaging	Het
Vps50	T	C	6: 3,592,433 (GRCm39)	S689P	probably benign	Het
Wipf2	A	G	11: 98,787,068 (GRCm39)	T366A	probably damaging	Het
Zfp128	T	C	7: 12,624,897 (GRCm39)	Y422H	possibly damaging	Het
Zfyve28	G	A	5: 34,373,932 (GRCm39)	T694I	probably benign	Het

Other mutations in Kcnq2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01063:Kcnq2	APN	2	180,751,582 (GRCm39)	unclassified	probably benign
IGL02064:Kcnq2	APN	2	180,750,819 (GRCm39)	missense	probably damaging	1.00
IGL02231:Kcnq2	APN	2	180,723,508 (GRCm39)	missense	probably benign	0.22
IGL02261:Kcnq2	APN	2	180,723,483 (GRCm39)	missense	probably damaging	0.98
IGL02510:Kcnq2	APN	2	180,723,154 (GRCm39)	missense	probably benign
IGL02583:Kcnq2	APN	2	180,723,295 (GRCm39)	missense	probably benign	0.01
IGL02627:Kcnq2	APN	2	180,724,120 (GRCm39)	unclassified	probably benign
IGL03303:Kcnq2	APN	2	180,724,182 (GRCm39)	missense	probably benign
R0269:Kcnq2	UTSW	2	180,738,767 (GRCm39)	missense	probably benign	0.00
R1535:Kcnq2	UTSW	2	180,776,618 (GRCm39)	missense	probably damaging	1.00
R1688:Kcnq2	UTSW	2	180,728,826 (GRCm39)	missense	probably damaging	1.00
R1776:Kcnq2	UTSW	2	180,742,350 (GRCm39)	missense	probably benign	0.01
R1946:Kcnq2	UTSW	2	180,730,244 (GRCm39)	missense	probably benign	0.09
R2105:Kcnq2	UTSW	2	180,723,145 (GRCm39)	missense	probably benign	0.03
R2382:Kcnq2	UTSW	2	180,753,900 (GRCm39)	missense	probably damaging	1.00
R2912:Kcnq2	UTSW	2	180,723,567 (GRCm39)	missense	probably damaging	1.00
R3826:Kcnq2	UTSW	2	180,746,693 (GRCm39)	missense	possibly damaging	0.56
R3898:Kcnq2	UTSW	2	180,751,479 (GRCm39)	missense	probably damaging	0.97
R4282:Kcnq2	UTSW	2	180,722,946 (GRCm39)	missense	probably damaging	1.00
R4938:Kcnq2	UTSW	2	180,728,766 (GRCm39)	missense	probably damaging	0.96
R4962:Kcnq2	UTSW	2	180,753,836 (GRCm39)	missense	possibly damaging	0.59
R5055:Kcnq2	UTSW	2	180,728,554 (GRCm39)	intron	probably benign
R5107:Kcnq2	UTSW	2	180,750,340 (GRCm39)	intron	probably benign
R5371:Kcnq2	UTSW	2	180,776,813 (GRCm39)	missense	probably damaging	1.00
R5557:Kcnq2	UTSW	2	180,776,690 (GRCm39)	missense	probably benign	0.07
R5839:Kcnq2	UTSW	2	180,751,544 (GRCm39)	missense	probably damaging	1.00
R5998:Kcnq2	UTSW	2	180,728,801 (GRCm39)	missense	probably damaging	1.00
R6084:Kcnq2	UTSW	2	180,729,449 (GRCm39)	missense	possibly damaging	0.53
R6207:Kcnq2	UTSW	2	180,755,026 (GRCm39)	missense	possibly damaging	0.49
R6744:Kcnq2	UTSW	2	180,727,099 (GRCm39)	missense	possibly damaging	0.94
R7018:Kcnq2	UTSW	2	180,723,517 (GRCm39)	nonsense	probably null
R7266:Kcnq2	UTSW	2	180,776,885 (GRCm39)	start codon destroyed	probably null	0.92
R7291:Kcnq2	UTSW	2	180,730,172 (GRCm39)	missense	possibly damaging	0.69
R7319:Kcnq2	UTSW	2	180,750,895 (GRCm39)	missense	probably damaging	1.00
R7447:Kcnq2	UTSW	2	180,754,887 (GRCm39)	missense	probably damaging	0.97
R7573:Kcnq2	UTSW	2	180,723,382 (GRCm39)	missense	probably benign	0.04
R7897:Kcnq2	UTSW	2	180,722,934 (GRCm39)	missense	probably damaging	1.00
R8942:Kcnq2	UTSW	2	180,724,244 (GRCm39)	missense	probably damaging	1.00
R9394:Kcnq2	UTSW	2	180,724,217 (GRCm39)	missense	probably benign
R9516:Kcnq2	UTSW	2	180,776,753 (GRCm39)	missense	probably benign	0.00
R9544:Kcnq2	UTSW	2	180,729,407 (GRCm39)	missense	probably damaging	1.00
R9592:Kcnq2	UTSW	2	180,728,813 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGCTCTCTAGGGTCTGTAAACC -3'
(R):5'- GTACAGCTGAAGTCTGAATGACC -3'

Sequencing Primer
(F):5'- GTCCAAGTTCACAGTTCACAGGTG -3'
(R):5'- GTCTGAATGACCATCAGTGTCCAG -3'

Posted On

2022-04-18