Paralogue Annotation for KCNQ1 residue 555

Residue details

Gene: KCNQ1
Reference Sequences: LRG: LRG_287, Ensembl variant: ENST00000155840 / ENSP00000155840
Amino Acid Position: 555
Reference Amino Acid: R - Arginine
Protein Domain: C-terminus


Paralogue Variants mapped to KCNQ1 residue 555

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNQ2R581GInfantile spasmsMedium2 25262651
KCNQ2R581XEpilepsy, benign neonatalMedium2 14534157, 25525159

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.



KCNQ1AKKKFQQARKPYDVRDVIEQYSQGHLNLMV>R<IKELQRRLDQSIGKPSLFIS----------575
KCNQ2SKRKFKESLRPYDVMDVIEQYSAGHLDMLS>R<IKSLQSRVDQIVGRGPAITD--KDR--T--605
KCNQ3YKKKFKETLRPYDVKDVIEQYSAGHLDMLS>R<IKYLQTRIDMIFTPGPPSTP--KHKKSQKG588
KCNQ4AKRKFKETLRPYDVKDVIEQYSAGHLDMLG>R<IKSLQTRVDQIVGRGPGDRKAREKG--D--601
KCNQ5AKRKFKETLRPYDVKDVIEQYSAGHLDMLC>R<IKSLQTRVDQILGKGQITSD-KKSR--E--588
KCNA1------------------------------>-<------------------------------
KCNA10------------------------------>-<------------------------------
KCNA2------------------------------>-<------------------------------
KCNA3------------------------------>-<------------------------------
KCNA4------------------------------>-<------------------------------
KCNA5------------------------------>-<------------------------------
KCNA6------------------------------>-<------------------------------
KCNA7------------------------------>-<------------------------------
KCNB1------DPSPLLPVLGMYHDPLRNRGSAAA>A<VAGLECA-----------------------711
KCNB2GSAPQTPPSTARPLPVTTADFSLTTPQHIS>T<ILLEETP-----------------------761
KCNC1GEYACPPGGGMRK----------DLCKESP>-<--VIAKY-----------------------576
KCNC2GDYTCASDGGIRKG----YEKSRSLNNIAG>L<AGNALRL-----------------------614
KCNC3-DYAPSPDGSIRKATGAPPLPPQDWRKPGP>P<S-FLPDL-----------------------747
KCNC4GDYACA-DGSVRKG----TFVLRDLPLQHS>P<---EAAC-----------------------624
KCND1LA--GLRRSHAPQSRSSLNAKPHDSLDLNC>D<SRDFVAA-----------------------597
KCND2IQIRCVERTPLSNSRSSLNAKMEECVKLNC>E<QPYVTTA-----------------------596
KCND3IHIQGSEQPSLTTSRSSLNLKADDGLRPNC>K<TSQITTA-----------------------613
KCNF1------------------------------>-<------------------------------
KCNG1------------------------------>-<------------------------------
KCNG2------------------------------>-<------------------------------
KCNG3------------------------------>-<------------------------------
KCNG4------------------------------>-<------------------------------
KCNS1------------------------------>-<------------------------------
KCNS2------------------------------>-<------------------------------
KCNS3------------------------------>-<------------------------------
KCNV1------------------------------>-<------------------------------
KCNV2------------------------------>-<------------------------------
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNQ1

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R555Cc.1663C>T Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation. 1997 96(9):2778-81. 9386136
Inherited ArrhythmiaLQTS Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome. Pacing Clin Electrophysiol. 2003 26(8):1660-7. 12877697
Inherited ArrhythmiaLQTS Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 82(3):182-8. 14760488
Inherited ArrhythmiaLQTS Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476
Inherited ArrhythmiaLQTS Kv7.1 (KCNQ1) properties and channelopathies. J Physiol. 2008 586(7):1785-9. 18174212
Inherited ArrhythmiaLQTS Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085
Inherited ArrhythmiaLQTS PKA and PKC partially rescue long QT type 1 phenotype by restoring channel-PIP2 interactions. Channels (Austin). 2010 4(1):3-11. 19934648
Inherited ArrhythmiaLQTS Impaired KCNQ1-KCNE1 and phosphatidylinositol-4,5-bisphosphate interaction underlies the long QT syndrome. Circ Res. 2005 96(7):730-9. 15746441
Inherited ArrhythmiaLQTS Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. Circulation. 2012 125(16):1988-96. 22456477
Inherited ArrhythmiaLQTS A long QT mutation substitutes cholesterol for phosphatidylinositol-4,5-bisphosphate in KCNQ1 channel regulation. PLoS One. 2014 9(3):e93255. doi: 10.1371/journal.pone.0093255. eC 24681627
Inherited ArrhythmiaLQTS Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP₂. J Cell Sci. 2014 127(Pt 18):3943-55. doi: 10.1242/jcs.147033. 25037568
Inherited ArrhythmiaLQTS Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 16(17):5472-9. 9312006
p.R555Hc.1664G>A Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations. J Am Coll Cardiol. 2004 43(5):826-30. 14998624
Inherited ArrhythmiaLQTS Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476
Inherited ArrhythmiaLQTS Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085
Inherited ArrhythmiaLQTS Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS [Neonatal forms of congenital long QT syndrome]. Arch Mal Coeur Vaiss. 2004 97(5):479-83. 15214551
Inherited ArrhythmiaLQTS Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome. Circ Cardiovasc Genet. 2012 5(5):519-28. doi: 10.1161/CIRCGENETICS.112.963785. 22949429
Inherited ArrhythmiaLQTS Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP₂. J Cell Sci. 2014 127(Pt 18):3943-55. doi: 10.1242/jcs.147033. 25037568
Inherited ArrhythmiaLQTS LQT1 mutations in KCNQ1 C-terminus assembly domain suppress IKs using different mechanisms. Cardiovasc Res. 2014 104(3):501-11. doi: 10.1093/cvr/cvu231. 25344363
p.R555Sc.1663C>A Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085