Paralogue Annotation for KCNH2 residue 531

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 531
Reference Amino Acid: R - Arginine
Protein Domain: Transmembrane/Linker/Pore


Paralogue Variants mapped to KCNH2 residue 531

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CNGA3R283WColour-blindness, totalHigh6 9662398, 20238023, 24504161, 26992781
CNGA3R283QColour-blindness, totalHigh6 9662398, 25616768

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 KCNH2.



KCNH2-------------------LIGLLKTARLL>R<LVRVARKLDRY-----SEYGAAV-LFLLMC555
KCNH1Q---IPPPLEGRESQGISSLFSSLKVVRLL>R<LGRVARKLDHY-----IEYGAAV-LVLLVC384
KCNH3V---Y-------------FGAHLLKTVRLL>R<LLRLLPRLDRY-----SQYSAVV-LTLLMA365
KCNH4V---T-------------SLVHLLKTVRLL>R<LLRLLQKLERY-----SQCSAVV-LTLLMS367
KCNH5----------------ISSLFSSLKVVRLL>R<LGRVARKLDHY-----LEYGAAV-LVLLVC354
KCNH6T---T-------------TLIGLLKTARLL>R<LVRVARKLDRY-----SEYGAAV-LFLLMC406
KCNH7T---T-------------TLIGLLKTARLL>R<LVRVARKLDRY-----SEYGAAV-LMLLMC557
KCNH8V---V-------------SLVHLLKTVRLL>R<LLRLLQKLDRY-----SQHSTIV-LTLLMS361
CNGA1------------------PEIRLNRLLRFS>R<MFEFFQRTETR-----TNYPNIFRISNLVM305
CNGA2------------------PEVRFNRLLHFA>R<MFEFFDRTETR-----TNYPNIFRISNLVL280
CNGA3------------------PEVRFNRLLKFS>R<LFEFFDRTETR-----TNYPNMFRIGNLVL308
CNGA4------------------PTLRLNRFLRAP>R<LFEAFDRTETR-----TAYPNAFRIAKLML174
CNGB1------------------PLLRLPRCLKYM>A<FFEFNSRLESI-----LSKAYVYRVIRTTA796
CNGB3------------------PMFRANRMLKYT>S<FFEFNHHLESI-----MDKAYIYRVIRTTG358
HCN1IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVVRIFNLIG303
HCN2IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVMRICNLIS372
HCN3IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVVRIFNLIG256
HCN4IVRFT-------------KILSLLRLLRLS>R<LIRYIHQWEEIFHMTYDLASAVVRIVNLIG423
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNH2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R531Qc.1592G>A Inherited ArrhythmiaLQTSSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849
Inherited ArrhythmiaLQTS Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor. J Membr Biol. 2013 246(5):355-64. doi: 10.1007/s00232-013-9539-6. 23546015
p.R531Wc.1591C>T 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
Inherited ArrhythmiaLQTS Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor. J Membr Biol. 2013 246(5):355-64. doi: 10.1007/s00232-013-9539-6. 23546015