Paralogue Annotation for KCNH2 residue 176

Residue details

Gene: KCNH2
Reference Sequences: LRG: LRG_288, Ensembl variant: ENST00000262186 / ENSP00000262186
Amino Acid Position: 176
Reference Amino Acid: R - Arginine
Protein Domain: N-terminus


Paralogue Variants mapped to KCNH2 residue 176

No paralogue variants have been mapped to residue 176 for KCNH2.



KCNH2NHRGPPTSWLAPGRAKTFRLKLPALLALTA>R<ESSVRSGGAGGAGAPGAVVVDVDLTPAAPS206
KCNH1--------------CKGWG----------->-<------------------------------149
KCNH3--------------WKETGGGRR------->-<------------------------------153
KCNH4--------------GRGDSNHEN------->-<------------------------------154
KCNH5--------------TKGWT----------->-<------------------------------147
KCNH6---------LAKCSSRSLSQRLLSQSFLGS>E<GSHGRPGGPG--------------------167
KCNH7N----PILPIKTVNRKFFGFKFPGLRVLTY>R<KQSLPQEDPD------VVVIDS----SKHS191
KCNH8-----------------DKKEDK------->-<------------------------------149
CNGA1------------------------------>-<------------------------------
CNGA2------------------------------>-<------------------------------
CNGA3------------------------------>-<------------------------------
CNGA4------------------------------>-<------------------------------
CNGB1QVGVGQSEEDGTRPQSTSDQKLWEEVGEEA>K<KEAEEKAKEEAEEVAEEEAEKEPQDWAETK444
CNGB3----SRRNEEGSHPSNQSQQ----TTAQEE>N<KGEEKSLKTKSTPVTSEEPHTNIQDKLSKK76
HCN1--------------PAGG---F-------->-<------------------------------81
HCN2--------------EAGSEEAG-------->-<------------------------------150
HCN3---------------------G-------->-<------------------------------41
HCN4---------------AAGDQIL-------->-<------------------------------201
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNH2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R176Wc.526C>T ConflictSIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects. J Am Coll Cardiol. 1999 34(3):823-9. 10483966
Inherited ArrhythmiaLQTS Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects. Hum Mutat. 2000 15(6):580-1. 10862094
Putative Benign Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc. 2003 78(12):1479-87. 14661677
Inherited ArrhythmiaLQTS Allelic dropout in long QT syndrome genetic testing: a possible mechanism underlying false-negative results. Heart Rhythm. 2006 3(7):815-21. 16818214
Other Cardiac Phenotype Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. Am Heart J. 2006 152(6):1116-22. 17161064
Inherited ArrhythmiaLQTS High prevalence of four long QT syndrome founder mutations in the Finnish population. Ann Med. 2009 41(3):234-40. 19160088
Benign Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
Inherited ArrhythmiaLQTS The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat. 2009 30(11):1486-511. 19862833
Inherited ArrhythmiaLQTS Molecular characterization of two founder mutations causing long QT syndrome and identification of compound heterozygous patients. Ann Med. 2006 38(4):294-304. 16754261
Inherited ArrhythmiaLQTS Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis Model Mech. 2012 5(2):220-30. doi: 10.1242/dmm.008409. 22052944
Inherited ArrhythmiaLQTS End-recovery QTc: a useful metric for assessing genetic variants of unknown significance in long-QT syndrome. J Cardiovasc Electrophysiol. 2012 23(6):637-42. doi: 10.1111/j.1540-8167.2011.02265. 22429796
Putative Benign 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 An in vivo cardiac assay to determine the functional consequences of putative long QT syndrome mutations. Circ Res. 2013 112(5):826-30. doi: 10.1161/CIRCRESAHA.112.300664. 23303164
Inherited ArrhythmiaLQTS A presumably benign human ether-a-go-go-related gene mutation (R176W) with a malignant primary manifestation of long QT syndrome. Cardiol Young. 2012 22(3):360-3. doi: 10.1017/S1047951111001831. 22067087
Unknown Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510