Paralogue Annotation for KCNQ1 residue 141

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 141
Reference Amino Acid: V - Valine
Protein Domain: Transmembrane/Linker/Pore

Paralogue Variants mapped to KCNQ1 residue 141

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
KCNA1	C185W	Episodic ataxia 1	Medium	9	23349320, 25642194, 25642194, 23349320

To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in KCNQ1.

KCNQ1	NFLERPT-GWKCFVYHFAVFLIVLVCLIFS>V<LSTIEQYA----------------------	149
KCNQ2	NVLERPR-G-WAFIYHAYVFLLVFSCLVLS>V<FSTIKEYE----------------------	119
KCNQ3	DALERPR-G-WALLYHALVFLIVLGCLILA>V<LTTFKEYE----------------------	149
KCNQ4	NVLERPR-G-WAFVYHVFIFLLVFSCLVLS>V<LSTIQEHQ----------------------	125
KCNQ5	NVLERPR-G-WAFIYHAFVFLLVFGCLILS>V<FSTIPEHT----------------------	153
KCNA1	LLFEYPESSGPARVIAIVSVMVILISIVIF>C<LETLPELKDDK-DF--------TG------	200
KCNA10	LLFEYPESSSAARAVAVVSVLVVVISITIF>C<LETLPEFREDR-EL--------KV------	249
KCNA2	LLFEYPESSGPARIIAIVSVMVILISIVSF>C<LETLPIFRDEN-ED--------MHGSG---	199
KCNA3	LLFEYPESSGPARGIAIVSVLVILISIVIF>C<LETLPEFRDEK-DY--------PA-ST---	269
KCNA4	LLFEYPESSSPARGIAIVSVLVILISIVIF>C<LETLPEFRDDR-DL--------VM-AL---	342
KCNA5	LIFEYPESSGSARAIAIVSVLVILISIITF>C<LETLPEFRDER-ELLRHPPAP---------	288
KCNA6	LLFEYPESSGPARGIAIVSVLVILISIVIF>C<LETLPQFRVDG-RGGNNGGVSRVS-PVSRG	220
KCNA7	LLFEFPESSQAARVLAVVSVLVILVSIVVF>C<LETLPDFRDDR-DGTGL-----AA-AA---	181
KCNB1	DLLEKPNSSVAAKILAIISIMFIVLSTIAL>S<LNTLPELQSLD-EF--------GQ------	222
KCNB2	DLLEKPNSSVAAKILAIVSILFIVLSTIAL>S<LNTLPELQETD-EF--------GQ------	226
KCNC1	ALFEDPYSSRYARYVAFASLFFILVSITTF>C<LETHERFNPIV-NK--------TE-I----	224
KCNC2	ALFEDPYSSRAARFIAFASLFFILVSITTF>C<LETHEAFNI---VK--------NK-T----	261
KCNC3	ALFEDPYSSRAARYVAFASLFFILISITTF>C<LETHEGFIHIS-NK--------TV-T----	324
KCNC4	ALFEDPYSSRAARVVAFASLFFILVSITTF>C<LETHEAFNI---DR-NV-----TE-I----	260
KCND1	RAFENPHTSTAALVFYYVTGFFIAVSVIAN>V<VETIPCRGSAR-RS--------SR------	219
KCND2	RAFENPHTSTMALVFYYVTGFFIAVSVIAN>V<VETVPCGS-SP-GH--------IK------	217
KCND3	RAFENPHTSTLALVFYYVTGFFIAVSVITN>V<VETVPCGT-VP-G---------SK------	214
KCNF1	KFLEKPESSCPARVVAVLSFLLILVSSVVM>C<MGTIPELQVLD-AE--------GN------	215
KCNG1	DMVERPHSGLPGKVFACLSVLFVTVTAVNL>S<VSTLPSLREEEE-Q--------GH------	260
KCNG2	DVVDNPHSGLAGKLFACVSVSFVAVTAVGL>C<LSTMPDIRAEEE-R--------GE------	210
KCNG3	RTFEEPTSSLAAQILASVSVVFVIVSMVVL>C<ASTLPDWRN-AAAD--------NR------	204
KCNG4	EMVENPQSGLPGKVFACLSILFVATTAVSL>C<VSTMPDLRAEED-Q--------GE------	254
KCNS1	LTMENPGYSLPSKLFSCVSISVVLASIAAM>C<IHSLPEYQARE-AA--------AA------	253
KCNS2	LALDNPGYSVLSRVFSILSILVVMGSIITM>C<LNSLPDFQIPD-SQ--------GN------	220
KCNS3	IRMENPAYCLSAKLIAISSLSVVLASIVAM>C<VHSMSEFQNED-GE----------------	216
KCNV1	NILEKPGSSTAARIFGVISIIFVVVSIINM>A<LMSAEL-----------------S------	235
KCNV2	NLMEKPFSSVAAKAIGVASSTFVLVSVVAL>A<LNTVEEMQQHS-GQ--------GE------	293
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See full Alignment of Paralogues

Known Variants in KCNQ1

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V141M	c.421G>A	Inherited Arrhythmia	LQTS,SQTS,AF	rs199472687	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	AF	De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc Res. 2005 68(3):433-40. 16109388
		Inherited Arrhythmia	AF	Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels. J Physiol. 2008 586(Pt 17):4179-91. 18599533
		Inherited Arrhythmia	AF	Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. J Gen Physiol. 2012 139(2):135-44. doi: 10.1085/jgp.201110672. 22250012
		Inherited Arrhythmia	LQTS	Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007 46(49):14141-52. 17999538
		Inherited Arrhythmia	SQTS	Long-term follow-up of a pediatric cohort with short QT syndrome. J Am Coll Cardiol. 2013 61(11):1183-91. doi: 10.1016/j.jacc.2012.12.025. 23375927
		Inherited Arrhythmia	AF	Selective targeting of gain-of-function KCNQ1 mutations predisposing to atrial fibrillation. Circ Arrhythm Electrophysiol. 2013 6(5):960-6. doi: 10.1161/CIRCEP.113.000439. 24006450
		Inherited Arrhythmia	AF	Short QT syndrome manifesting with neonatal atrial fibrillation and bradycardia. Cardiology. 2014 128(3):236-40. doi: 10.1159/000360758. 24818999