Paralogue Annotation for KCNQ1 residue 226

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 226
Reference Amino Acid: A - Alanine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 226

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2A196VEpilepsy, benign neonatalHigh8 17475800, 23360469, 23708187
KCNV2V375MCone dystrophy, autosomal recessiveMedium8 22264887

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.



KCNQ1VLCVG----------------SKGQVFATS>A<IRGIRFLQILRMLHVDRQGGTWRLLGSVVF256
KCNQ2VLAAG----------------SQGNVFATS>A<LRSLRFLQILRMIRMDRRGGTWKLLGSVVY226
KCNQ3VVAVG----------------NQGNVLA-T>S<LRSLRFLQILRMLRMDRRGGTWKLLGSAIC255
KCNQ4VIAAG----------------TQGNIFATS>A<LRSMRFLQILRMVRMDRRGGTWKLLGSVVY232
KCNQ5VVSAK----------------TQGNIFATS>A<LRSLRFLQILRMVRMDRRGGTWKLLGSVVY260
KCNA1TLGTEIAEQEG-------N-QKGEQATSLA>I<LRVIRLVRVFRIFKLSRHSKGLQILGQTLK320
KCNA10TLITELVQETEP---------SAQQNMSLA>I<LRIIRLVRVFRIFKLSRHSKGLQILGQTLK369
KCNA2TLGTELAEKPE-------DAQQGQQAMSLA>I<LRVIRLVRVFRIFKLSRHSKGLQILGQTLK322
KCNA3TLGTELAERQ----------GNGQQAMSLA>I<LRVIRLVRVFRIFKLSRHSKGLQILGQTLK392
KCNA4TLGTDLAQQQGG------GNGQQQQAMSFA>I<LRIIRLVRVFRIFKLSRHSKGLQILGHTLR472
KCNA5TLGTELAEQQ---PGGGGGGQNGQQAMSLA>I<LRVIRLVRVFRIFKLSRHSKGLQILGKTLQ428
KCNA6TLGTELVQQQEQQPASGGGGQNGQQAMSLA>I<LRVIRLVRVFRIFKLSRHSKGLQILGKTLQ370
KCNA7ALGTELARQR----------GVGQQAMSLA>I<LRVIRLVRVFRIFKLSRHSKGLQILGQTLR306
KCNB1TIFLTES---N--------KSVLQFQNVRR>V<VQIFRIMRILRILKLARHSTGLQSLGFTLR325
KCNB2TIFLTES---N--------KSVLQFQNVRR>V<VQIFRIMRILRILKLARHSTGLQSLGFTLR329
KCNC1EVGLSG-------------LSSKAAKDVLG>F<LRVVRFVRILRIFKLTRHFVGLRVLGHTLR339
KCNC2EVGLSG-------------LSSKAAKDVLG>F<LRVVRFVRILRIFKLTRHFVGLRVLGHTLR376
KCNC3EVGLSG-------------LSSKAAKDVLG>F<LRVVRFVRILRIFKLTRHFVGLRVLGHTLR442
KCNC4EVGLSG-------------LSSKAARDVLG>F<LRVVRFVRILRIFKLTRHFVGLRVLGHTLR375
KCND1GLLVP------------------KNDDVSG>A<FVTLRVFRVFRIFKFSRHSQGLRILGYTLK320
KCND2GLVMT------------------DNEDVSG>A<FVTLRVFRVFRIFKFSRHSQGLRILGYTLK318
KCND3GLVMT------------------NNEDVSG>A<FVTLRVFRVFRIFKFSRHSQGLRILGYTLK315
KCNF1SLTLTHL-----------GARMMELTNVQQ>A<VQALRIMRIARIFKLARHSSGLQTLTYALK318
KCNG1TLLVDGAAAGRR----KPGAGNSYLDKVGL>V<LRVLRALRILYVMRLARHSLGLQTLGLTAR371
KCNG2SLLLGL-----A----AGPGGTKLLERAGL>V<LRLLRALRVLYVMRLARHSLGLRSLGLTMR316
KCNG3SVLMTV-----------FTGENSQLQRAGV>T<LRVLRMMRIFWVIKLARHFIGLQTLGLTLK317
KCNG4SLAVSEEPPEDG----ERPSGSSYLEKVGL>V<LRVLRALRILYVMRLARHSLGLQTLGLTVR365
KCNS1TLLAGVALG-D--------QGGKEFGHLGK>V<VQVFRLMRIFRVLKLARHSTGLRSLGATLK370
KCNS2TLVVNLV---V--------ESTPTLANLGR>V<AQVLRLMRIFRILKLARHSTGLRSLGATLK323
KCNS3TLAVDTK---E--------EESEDIENMGK>V<VQILRLMRIFRILKLARHSVGLRSLGATLR318
KCNV1TLLVESLSG-S--------QTTQELENVGR>I<VQVLRLLRALRMLKLGRHSTGLRSLGMTIT340
KCNV2QLLLECFTGEGH----QRGQTVGSVGKVGQ>V<LRVMRLMRIFRILKLARHSTGLRAFGFTLR405
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.A226Vc.677C>T Inherited ArrhythmiaLQTSrs199472707SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan. J Am Coll Cardiol. 2004 44(1):117-25. 15234419
Inherited ArrhythmiaLQTS Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 115(19):2481-9. 17470695