Paralogue Annotation for KCNJ2 residue 218

Residue details

Gene: KCNJ2
Reference Sequences: LRG: LRG_328, Ensembl variant: ENST00000535240 / ENSP00000441848
Amino Acid Position: 218
Reference Amino Acid: R - Arginine
Protein Domain: C-terminus


Paralogue Variants mapped to KCNJ2 residue 218

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
KCNJ10R204HSeizures, generalizedHigh9 22782654
KCNJ11R206CHyperinsulinismHigh9 25555642

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 KCNJ2.



KCNJ2KRNETLVFSHNAVIAMRDGKLCLMWRVGNL>R<KSHLVEAHVRAQLLKSRITSEGEYIPLDQI248
KCNJ1KRAKTITFSKNAVISKRGGKLCLLIRVANL>R<KSLLIGSHIYGKLLKTTVTPEGETIILDQI247
KCNJ3KRAETLMFSEHAVISMRDGKLTLMFRVGNL>R<NSHMVSAQIRCKLLKSRQTPEGEFLPLDQL249
KCNJ4KRAQTLLFSHHAVISVRDGKLCLMWRVGNL>R<KSHIVEAHVRAQLIKPYMTQEGEYLPLDQR240
KCNJ5KRAETLMFSNNAVISMRDEKLCLMFRVGDL>R<NSHIVEASIRAKLIKSRQTKEGEFIPLNQT255
KCNJ6KRAETLVFSTHAVISMRDGKLCLMFRVGDL>R<NSHIVEASIRAKLIKSKQTSEGEFIPLNQT258
KCNJ8RRAETLIFSRHAVIAVRNGKLCFMFRVGDL>R<KSMIISASVRIQVVKKTTTPEGEVVPIHQL246
KCNJ9KRAATLVFSSHAVVSLRDGRLCLMFRVGDL>R<SSHIVEASIRAKLIRSRQTLEGEFIPLHQT226
KCNJ10KRAETIRFSQHAVVASHNGKPCLMIRVANM>R<KSLLIGCQVTGKLLQTHQTKEGENIRLNQV234
KCNJ11RRAETLIFSKHAVIALRHGRLCFMLRVGDL>R<KSMIISATIHMQVVRKTTSPEGEVVPLHQV236
KCNJ12KRAQTLLFSHNAVVALRDGKLCLMWRVGNL>R<KSHIVEAHVRAQLIKPRVTEEGEYIPLDQI249
KCNJ13NRAFSIRFTDTAVVAHMDGKPNLIFQVANT>R<PSPLTSVRVSAVLYQERENGK----L-YQT220
KCNJ14KRNETLVFSENAVVALRDHRLCLMWRVGNL>R<RSHLVEAHVRAQLLQPRVTPEGEYIPLDHQ253
KCNJ15KRAETIKFSHCAVITKQNGKLCLVIQVANM>R<KSLLIQCQLSGKLLQTHVTKEGERILLNQA233
KCNJ16KRAQTIRFSYFALIGMRDGKLCLMWRIGDF>R<PNHVVEGTVRAQLLRYTEDSEGRM-TMAFK236
cons                              > <                              

See full Alignment of Paralogues


Known Variants in KCNJ2

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.R218Qc.653G>A Inherited ArrhythmiaLQTSrs199473384SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell. 2001 105(4):511-9. 11371347
Inherited ArrhythmiaLQTS Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest. 2002 110(3):381-8. 12163457
Inherited ArrhythmiaLQTS Mutations of KCNJ2 gene associated with Andersen-Tawil syndrome in Korean families. J Hum Genet. 2007 52(3):280-3. 17211524
Inherited ArrhythmiaLQTS Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome. Hum Mutat. 2007 28(2):208. 17221872
Inherited ArrhythmiaLQTS Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome. FASEB J. 2012 26(2):513-22. 22002906
Inherited ArrhythmiaLQTS Andersen mutations of KCNJ2 suppress the native inward rectifier current IK1 in a dominant-negative fashion. Cardiovasc Res. 2003 59(2):321-7. 12909315
Inherited ArrhythmiaLQTS Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome. J Biol Chem. 2003 278(51):51779-85. 14522976
Inherited ArrhythmiaLQTS Coexistence of Andersen-Tawil Syndrome with Polymorphisms in hERG1 Gene (K897T) and SCN5A Gene (H558R) in One Family. Ann Noninvasive Electrocardiol. 2015 26109178
p.R218Wc.652C>T Inherited ArrhythmiaLQTSrs104894578SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell. 2001 105(4):511-9. 11371347
Inherited ArrhythmiaLQTS Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest. 2002 110(3):381-8. 12163457
Inherited ArrhythmiaLQTS PIP2 binding residues of Kir2.1 are common targets of mutations causing Andersen syndrome. Neurology. 2003 60(11):1811-6. 12796536
Inherited ArrhythmiaLQTS KCNJ2 mutation in intractable ventricular arrhythmia with Andersen's syndrome. Pediatr Int. 2005 47(2):220-3. 15852530
Inherited ArrhythmiaLQTS Andersen-Tawil syndrome: new potassium channel mutations and possible phenotypic variation. Neurology. 2005 65(7):1083-9. 16217063
Inherited ArrhythmiaLQTS A family with Andersen-Tawil syndrome and dilated cardiomyopathy. Heart Rhythm. 2006 3(11):1346-50. 17074642
Inherited ArrhythmiaLQTS Andersen syndrome: an association of periodic paralysis, cardiac arrhythmia and dysmorphic abnormalities. Arq Neuropsiquiatr. 2006 64(3A):582-4. 17119796
Inherited ArrhythmiaLQTS Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome. Hum Mutat. 2007 28(2):208. 17221872
Inherited ArrhythmiaLQTS Flecainide for recurrent malignant ventricular arrhythmias in two siblings with Andersen-Tawil syndrome. Heart Rhythm. 2007 4(4):508-11. 17399642
Inherited ArrhythmiaLQTS Andersen-Tawil syndrome: management challenges during pregnancy, labor, and delivery. J Cardiovasc Electrophysiol. 2008 19(9):987-9. 18554214
Inherited ArrhythmiaLQTS Muscle weakness, palpitations and a small chin: the Andersen-Tawil syndrome. Pract Neurol. 2010 10(4):227-31. 20647529
Inherited ArrhythmiaLQTS Andersen mutations of KCNJ2 suppress the native inward rectifier current IK1 in a dominant-negative fashion. Cardiovasc Res. 2003 59(2):321-7. 12909315
Inherited ArrhythmiaLQTS Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory. Genet Test Mol Biomarkers. 2013 17(7):553-61. doi: 10.1089/gtmb.2012.0118. 23631430
Inherited ArrhythmiaLQTS Andersen-Tawil syndrome with early fixed myopathy. J Clin Neuromuscul Dis. 2014 16(2):79-82. doi: 10.1097/CND.0000000000000052. 25415519
p.Arg218Leuc.653G>T UnknownSIFT:
Polyphen: