Paralogue Annotation for KCNQ1 residue 229

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 229
Reference Amino Acid: G - Glycine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNQ1 residue 229

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNV2V378ICone dystrophy, autosomal recessiveMedium9 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.



KCNQ1VG----------------SKGQVFATSAIR>G<IRFLQILRMLHVDRQGGTWRLLGSVVFIHR259
KCNQ2AG----------------SQGNVFATSALR>S<LRFLQILRMIRMDRRGGTWKLLGSVVYAHS229
KCNQ3VG----------------NQGNVLA-TSLR>S<LRFLQILRMLRMDRRGGTWKLLGSAICAHS258
KCNQ4AG----------------TQGNIFATSALR>S<MRFLQILRMVRMDRRGGTWKLLGSVVYAHS235
KCNQ5AK----------------TQGNIFATSALR>S<LRFLQILRMVRMDRRGGTWKLLGSVVYAHS263
KCNA1TEIAEQEG-------N-QKGEQATSLAILR>V<IRLVRVFRIFKLSRHSKGLQILGQTLKASM323
KCNA10TELVQETEP---------SAQQNMSLAILR>I<IRLVRVFRIFKLSRHSKGLQILGQTLKASM372
KCNA2TELAEKPE-------DAQQGQQAMSLAILR>V<IRLVRVFRIFKLSRHSKGLQILGQTLKASM325
KCNA3TELAERQ----------GNGQQAMSLAILR>V<IRLVRVFRIFKLSRHSKGLQILGQTLKASM395
KCNA4TDLAQQQGG------GNGQQQQAMSFAILR>I<IRLVRVFRIFKLSRHSKGLQILGHTLRASM475
KCNA5TELAEQQ---PGGGGGGQNGQQAMSLAILR>V<IRLVRVFRIFKLSRHSKGLQILGKTLQASM431
KCNA6TELVQQQEQQPASGGGGQNGQQAMSLAILR>V<IRLVRVFRIFKLSRHSKGLQILGKTLQASM373
KCNA7TELARQR----------GVGQQAMSLAILR>V<IRLVRVFRIFKLSRHSKGLQILGQTLRASM309
KCNB1LTES---N--------KSVLQFQNVRRVVQ>I<FRIMRILRILKLARHSTGLQSLGFTLRRSY328
KCNB2LTES---N--------KSVLQFQNVRRVVQ>I<FRIMRILRILKLARHSTGLQSLGFTLRRSY332
KCNC1LSG-------------LSSKAAKDVLGFLR>V<VRFVRILRIFKLTRHFVGLRVLGHTLRAST342
KCNC2LSG-------------LSSKAAKDVLGFLR>V<VRFVRILRIFKLTRHFVGLRVLGHTLRAST379
KCNC3LSG-------------LSSKAAKDVLGFLR>V<VRFVRILRIFKLTRHFVGLRVLGHTLRAST445
KCNC4LSG-------------LSSKAARDVLGFLR>V<VRFVRILRIFKLTRHFVGLRVLGHTLRAST378
KCND1VP------------------KNDDVSGAFV>T<LRVFRVFRIFKFSRHSQGLRILGYTLKSCA323
KCND2MT------------------DNEDVSGAFV>T<LRVFRVFRIFKFSRHSQGLRILGYTLKSCA321
KCND3MT------------------NNEDVSGAFV>T<LRVFRVFRIFKFSRHSQGLRILGYTLKSCA318
KCNF1LTHL-----------GARMMELTNVQQAVQ>A<LRIMRIARIFKLARHSSGLQTLTYALKRSF321
KCNG1VDGAAAGRR----KPGAGNSYLDKVGLVLR>V<LRALRILYVMRLARHSLGLQTLGLTARRCT374
KCNG2LGL-----A----AGPGGTKLLERAGLVLR>L<LRALRVLYVMRLARHSLGLRSLGLTMRRCA319
KCNG3MTV-----------FTGENSQLQRAGVTLR>V<LRMMRIFWVIKLARHFIGLQTLGLTLKRCY320
KCNG4VSEEPPEDG----ERPSGSSYLEKVGLVLR>V<LRALRILYVMRLARHSLGLQTLGLTVRRCT368
KCNS1AGVALG-D--------QGGKEFGHLGKVVQ>V<FRLMRIFRVLKLARHSTGLRSLGATLKHSY373
KCNS2VNLV---V--------ESTPTLANLGRVAQ>V<LRLMRIFRILKLARHSTGLRSLGATLKYSY326
KCNS3VDTK---E--------EESEDIENMGKVVQ>I<LRLMRIFRILKLARHSVGLRSLGATLRHSY321
KCNV1VESLSG-S--------QTTQELENVGRIVQ>V<LRLLRALRMLKLGRHSTGLRSLGMTITQCY343
KCNV2LECFTGEGH----QRGQTVGSVGKVGQVLR>V<MRLMRIFRILKLARHSTGLRAFGFTLRQCY408
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G229Dc.686G>A Inherited ArrhythmiaLQTS,AFrs199472708SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet. 2009 54(2):115-21. 19165230
Inherited ArrhythmiaLQTS RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science. 2015 347(6218):1254806. doi: 10.1126/science.1254806. 25525159
Inherited ArrhythmiaLQTS Computational simulations of the effects of the G229D KCNQ1 mutation on human atrial fibrillation. J Physiol Sci. 2016 66(5):407-15. doi: 10.1007/s12576-016-0438-3. 26922794