Gene Symbol: KCNQ1OT1
Description: KCNQ1 opposite strand/antisense transcript 1 (non-protein coding)
Alias: KCNQ1-AS2, KCNQ10T1, KvDMR1, KvLQT1-AS, LIT1, NCRNA00012
Species: human
Products:     KCNQ1OT1

Top Publications

  1. Mitsuya K, Meguro M, Lee M, Katoh M, Schulz T, Kugoh H, et al. LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. Hum Mol Genet. 1999;8:1209-17 pubmed
    ..The transcript, called LIT1 (long QT intronic transcript 1), was expressed preferentially from the paternal allele and produced in most human ..
  2. Smilinich N, Day C, Fitzpatrick G, Caldwell G, Lossie A, Cooper P, et al. A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proc Natl Acad Sci U S A. 1999;96:8064-9 pubmed
    ..We have identified an evolutionarily conserved, maternally methylated CpG island (KvDMR1) in an intron of the KvLQT1 gene...
  3. Mohammad F, Pandey R, Nagano T, Chakalova L, Mondal T, Fraser P, et al. Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region. Mol Cell Biol. 2008;28:3713-28 pubmed publisher
    The Kcnq1ot1 antisense noncoding RNA has been implicated in long-range bidirectional silencing, but the underlying mechanisms remain enigmatic...
  4. Pandey R, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell. 2008;32:232-46 pubmed publisher
    ..Here we show that Kcnq1ot1 is an RNA polymerase II-encoded, 91 kb-long, moderately stable nuclear transcript and that its stability is ..
  5. Debaun M, Niemitz E, Feinberg A. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003;72:156-60 pubmed
    ..six of the children indicate that five of the six have specific epigenetic alterations associated with BWS-four at LIT1 and one at both LIT1 and H19...
  6. Gicquel C, Gaston V, Mandelbaum J, Siffroi J, Flahault A, Le Bouc Y. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet. 2003;72:1338-41 pubmed
  7. Lee M, DeBaun M, Mitsuya K, Galonek H, Brandenburg S, Oshimura M, et al. Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting. Proc Natl Acad Sci U S A. 1999;96:5203-8 pubmed
    ..We now show that an antisense orientation transcript within KVLQT1, termed LIT1 (long QT intronic transcript 1) is expressed normally from the paternal allele, from which KVLQT1 transcription is ..
  8. Shin J, Fitzpatrick G, Higgins M. Two distinct mechanisms of silencing by the KvDMR1 imprinting control region. EMBO J. 2008;27:168-78 pubmed
    ..The KvDMR1 ICR contains both the promoter for the Kcnq1ot1 ncRNA and two CTCF-binding sites located within sequences exhibiting repressive activity in enhancer-blocking ..
  9. Arima T, Kamikihara T, Hayashida T, Kato K, Inoue T, Shirayoshi Y, et al. ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome. Nucleic Acids Res. 2005;33:2650-60 pubmed
    ..ZAC, a sequence-specific DNA-binding protein, binds within the CpG island of LIT1 (KCNQ1OT1), a paternally expressed, anti-sense RNA thought to negatively regulate p57(KIP2) in cis...

More Information


  1. Diaz Meyer N, Day C, Khatod K, Maher E, Cooper W, Reik W, et al. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. J Med Genet. 2003;40:797-801 pubmed
    ..5. The most frequent alteration associated with BWS is the absence of methylation at the maternal allele of KvDMR1, an intronic CpG island within the KCNQ1 gene...
  2. Sunamura N, Ohira T, Kataoka M, Inaoka D, Tanabe H, Nakayama Y, et al. Regulation of functional KCNQ1OT1 lncRNA by β-catenin. Sci Rep. 2016;6:20690 pubmed publisher
    ..We previously reported that KCNQ1OT1, an imprinted antisense lncRNA in the human KCNQ1 locus on chromosome 11p15...
  3. Cerrato F, Vernucci M, Pedone P, Chiariotti L, Sebastio G, Bruni C, et al. The 5' end of the KCNQ1OT1 gene is hypomethylated in the Beckwith-Wiedemann syndrome. Hum Genet. 2002;111:105-7 pubmed
  4. Niemitz E, Debaun M, Fallon J, Murakami K, Kugoh H, Oshimura M, et al. Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome. Am J Hum Genet. 2004;75:844-9 pubmed
    ..including infrequent mutation of p57(KIP2) or loss of imprinting of either of two imprinted gene domains on 11p15: LIT1, which is near p57(KIP2), or H19/IGF2...
  5. Gomes M, Huber J, Ferriani R, Amaral Neto A, Ramos E. Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologies. Mol Hum Reprod. 2009;15:471-7 pubmed publisher
    ..sperm injection (ICSI)] on the epigenetic reprogramming of the maternally methylated imprinting control region KvDMR1 in clinically normal children...
  6. Peng H, Chang S, Chao A, Wang C, Cheng P, Hwang S, et al. DNA methylation patterns of imprinting centers for H19, SNRPN, and KCNQ1OT1 in single-cell clones of human amniotic fluid mesenchymal stem cell. Taiwan J Obstet Gynecol. 2012;51:342-9 pubmed publisher
    To test the hypothesis that human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature in imprinting centers of H19, SNRPN, and KCNQ1OT1 during in vitro cell culture.
  7. Geuns E, Hilven P, Van Steirteghem A, Liebaers I, De Rycke M. Methylation analysis of KvDMR1 in human oocytes. J Med Genet. 2007;44:144-7 pubmed
    ..syndrome compared with the general population, and in most of these patients, aberrant methylation imprints of KvDMR1 have been found...
  8. Khoueiry R, Ibala Romdhane S, Al Khtib M, Blachère T, Lornage J, Guerin J, et al. Abnormal methylation of KCNQ1OT1 and differential methylation of H19 imprinting control regions in human ICSI embryos. Zygote. 2013;21:129-38 pubmed publisher
    ..normally following intracytoplasmic sperm injection (ICSI), we analysed the methylation profile of H19 and KCNQ1OT1 imprinting control regions, H19DMR and KvDMR1 respectively, in high-grade blastocysts and in embryos that ..
  9. Khoueiry R, Khoureiry R, Ibala Rhomdane S, Mery L, Blachère T, Guerin J, et al. Dynamic CpG methylation of the KCNQ1OT1 gene during maturation of human oocytes. J Med Genet. 2008;45:583-8 pubmed publisher
    ..We examined the methylation of the KCNQ1OT1 differentially methylated region (KvDMR1) in human oocytes at different stages of their development: germinal ..
  10. Guseva N, Mondal T, Kanduri C. Antisense noncoding RNA promoter regulates the timing of de novo methylation of an imprinting control region. Dev Biol. 2012;361:403-11 pubmed publisher
    ..Here, we show that a paternal allele of Kcnq1 ICR lacking the Kcnq1ot1 promoter remains unmethylated during spermatogenesis; however, it becomes methylated specifically during pre-..
  11. He J, Kelly T, Zhao Q, Li H, Huang J, Wang L, et al. Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese. Circ Cardiovasc Genet. 2013;6:598-607 pubmed publisher
    ..Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline. ..
  12. Senniappan S, Ismail D, Shipster C, Beesley C, Hussain K. The heterogeneity of hyperinsulinaemic hypoglycaemia in 19 patients with Beckwith-Wiedemann syndrome due to KvDMR1 hypomethylation. J Pediatr Endocrinol Metab. 2015;28:83-6 pubmed publisher
    ..5. Hypomethylation of KvDMR1 on the maternal allele is the most common genetic cause, and hyperinsulinaemic hypoglycaemia (HH) is the most ..
  13. Mayo S, Monfort S, Roselló M, Oltra S, Orellana C, Martínez F. In Pursuit of New Imprinting Syndromes by Epimutation Screening in Idiopathic Neurodevelopmental Disorder Patients. Biomed Res Int. 2015;2015:341986 pubmed publisher
    ..with syndromic ID/autism we found five patients with altered methylation in the four genes studied: MEG3, H19, KCNQ1OT1, and SNRPN...
  14. Coto E, Calvo D, Reguero J, Moris C, Rubín J, Diaz Corte C, et al. Differential methylation of lncRNA KCNQ1OT1 promoter polymorphism was associated with symptomatic cardiac long QT. Epigenomics. 2017;9:1049-1057 pubmed publisher
    To investigate whether the differential methylation of KCNQ1OT1 was associated with the risk of symptomatic long QTc. We investigated the methylation status of KCNQ1OT1 in a cohort of patients (n = 131) with a symptomatic prolonged QTc...
  15. Bedeschi M, Calvello M, Paganini L, Pezzani L, Baccarin M, Fontana L, et al. Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated region in isolated omphalocele cases. BMC Med Genet. 2017;18:115 pubmed publisher
    ..and most frequent clinical manifestation of Beckwith-Wiedemann Syndrome (BWS) in case of loss of methylation at KCNQ1OT1: Transcription Star Site-Differentially Methylated Region (TSS-DMR) or in presence of CDKN1C mutations...
  16. Chiesa N, De Crescenzo A, Mishra K, Perone L, Carella M, Palumbo O, et al. The KCNQ1OT1 imprinting control region and non-coding RNA: new properties derived from the study of Beckwith-Wiedemann syndrome and Silver-Russell syndrome cases. Hum Mol Genet. 2012;21:10-25 pubmed publisher
    ..It includes the centromeric ICR (ICR2) and the most 5' 20 kb of the non-coding KCNQ1OT1 gene. Its maternal transmission is associated with ICR2 hypomethylation and the BWS phenotype...
  17. Du M, Zhou W, Beatty L, Weksberg R, Sadowski P. The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15.5. Genomics. 2004;84:288-300 pubmed
    ..A differentially methylated region in ICR2 regulates the expression of a long transcript called KCNQ1OT1. This paternally expressed transcript negatively regulates several paternally imprinted genes around ICR2...
  18. Nakano S, Murakami K, Meguro M, Soejima H, Higashimoto K, Urano T, et al. Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci. 2006;97:1147-54 pubmed
    The human chromosome region 11p15.5 contains a number of maternally and paternally imprinted genes, and the LIT1/KCNQ1OT1 locus acts as an imprinting center in the proximal domain of 11p15.5...
  19. Debaun M, Niemitz E, McNeil D, Brandenburg S, Lee M, Feinberg A. Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet. 2002;70:604-11 pubmed
    ..The most common constitutional abnormalities in BWS are epigenetic, involving abnormal methylation of either H19 or LIT1, which encode untranslated RNAs on 11p15...
  20. Gou C, Liu X, Shi X, Chai H, He Z, Huang X, et al. Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction. Twin Res Hum Genet. 2017;20:389-394 pubmed publisher
    CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development...
  21. Jin X, Jin H, Shi Y, Guo Y, Zhang H. Long Non-Coding RNA KCNQ1OT1 Promotes Cataractogenesis via miR-214 and Activation of the Caspase-1 Pathway. Cell Physiol Biochem. 2017;42:295-305 pubmed publisher
    b>KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain...
  22. Andresini O, Ciotti A, Rossi M, Battistelli C, Carbone M, Maione R. A cross-talk between DNA methylation and H3 lysine 9 dimethylation at the KvDMR1 region controls the induction of Cdkn1c in muscle cells. Epigenetics. 2016;11:791-803 pubmed
    ..of the bHLH myogenic factor MyoD to a long-distance regulatory element within the imprinting control region KvDMR1. Interestingly, MyoD binding to KvDMR1 is prevented in myogenic cell types refractory to the induction of Cdkn1c...
  23. Zhang Z, Weaver D, Olsen D, deKay J, Peng Z, Ashikaga T, et al. Long non-coding RNA chromogenic in situ hybridisation signal pattern correlation with breast tumour pathology. J Clin Pathol. 2016;69:76-81 pubmed publisher
    ..Staining was graded by modified Allred scoring. HOTAIR, H19 and KCNQ1OT1 had significantly higher expression levels in IBC and DCIS than NA (p<0...
  24. Pauler F, Barlow D, Hudson Q. Mechanisms of long range silencing by imprinted macro non-coding RNAs. Curr Opin Genet Dev. 2012;22:283-9 pubmed publisher
    ..It is timely, however, to consider alternative explanations consistent with the published data, whereby transcription alone could cause gene silencing at a distance. ..
  25. Wan J, Huang M, Zhao H, Wang C, Zhao X, Jiang X, et al. A novel tetranucleotide repeat polymorphism within KCNQ1OT1 confers risk for hepatocellular carcinoma. DNA Cell Biol. 2013;32:628-34 pubmed publisher
    KCNQ1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA responsible for silencing a cluster of genes in cis, has been shown to be involved in multiple cancers...
  26. Lin H, Chuang C, Tu R, Fang Y, Su Y, Chen C, et al. Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome. Mol Genet Metab. 2016;119:8-13 pubmed publisher
    ..referred for diagnostic testing based on methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-..
  27. Shen W, Xing F, Kong L, Chen S, Li H. Expression of imprinted genes related to Beckwith-Wiedemann syndrome in human oocytes and preimplantation embryos. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005;22:265-7 pubmed
    ..Using nested reverse transcription-PCR to analyze the expression of P57KIP2, LIT1, TSSC3 in human oocytes and preimplantation embryos...
  28. Mohammad F, Mondal T, Kanduri C. Epigenetics of imprinted long noncoding RNAs. Epigenetics. 2009;4:277-86 pubmed
    ..Recent emerging evidence indicates that long ncRNAs such as Kcnq1ot1 and Air which map to the Kcnq1 and Igf2r imprinted gene clusters, respectively, mediate the transcriptional ..
  29. Demars J, Rossignol S, Netchine I, Lee K, Shmela M, Faivre L, et al. New insights into the pathogenesis of Beckwith-Wiedemann and Silver-Russell syndromes: contribution of small copy number variations to 11p15 imprinting defects. Hum Mutat. 2011;32:1171-82 pubmed publisher
    ..of them under the control of its own imprinting control region (ICR1 for the IGF2/H19 domain and ICR2 for the KCNQ1OT1/CDKN1C domain)...
  30. Wijnen M, Alders M, Zwaan C, Wagner A, van den Heuvel Eibrink M. KCNQ1OT1 hypomethylation: a novel disguised genetic predisposition in sporadic pediatric adrenocortical tumors?. Pediatr Blood Cancer. 2012;59:565-6 pubmed publisher
    ..In both patients genetic screening revealed hypomethylation of the KCNQ1OT1 gene, well-known for its association with the Beckwith-Wiedemann syndrome...
  31. Kanduri C. Kcnq1ot1: a chromatin regulatory RNA. Semin Cell Dev Biol. 2011;22:343-50 pubmed publisher
    ..b>Kcnq1ot1 is one such long chromatin-interacting ncRNA that silences multiple genes in the Kcnq1 domain by establishing a ..
  32. Murphy R, Thompson J, Tost J, Mitchell E. No evidence for copy number and methylation variation in H19 and KCNQ10T1 imprinting control regions in children born small for gestational age. BMC Med Genet. 2014;15:67 pubmed publisher
    ..common variation in copy number in the BWS/SRS 11p15 region or altered methylation levels at IGF2/H19 ICR or KCNQ10T1 ICR was associated with SGA...
  33. Khositseth A, Tester D, Will M, Bell C, Ackerman M. Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. Heart Rhythm. 2004;1:60-4 pubmed
    ..Along with previous gene-specific associations involving swimming and LQT1 as well as auditory triggers and LQT2, this association between postpartum cardiac events and LQT2 can facilitate strategic genotyping. ..
  34. Sazhenova E, Lebedev I. [Epimutations of the KCNQ1OT1 imprinting center of chromosome 11 in early human embryo lethality]. Genetika. 2008;44:1609-16 pubmed
    Disturbance of the epigenetic status of the H19 and KCNQ1OT1 imprinting centers of chromosome 11 and the CDKN1C imprinted gene in early human embryolethality have been studied...
  35. Pick M, Stelzer Y, Bar Nur O, Mayshar Y, Eden A, Benvenisty N. Clone- and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells. 2009;27:2686-90 pubmed publisher
    ..However, we found biallelic expression of the H19 gene in one iPS cell line and biallelic expression of the KCNQ10T1 gene in another iPS cell line...
  36. Higashimoto K, Soejima H, Saito T, Okumura K, Mukai T. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer. Cytogenet Genome Res. 2006;113:306-12 pubmed
    ..5, which is homologous to mouse chromosome region 7F5, is a well-known imprinted region. The CDKN1C/KCNQ1OT1 imprinted domain, which is one of two imprinted domains at 11p15...
  37. Ng M, Shriner D, Chen B, Li J, Chen W, Guo X, et al. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genet. 2014;10:e1004517 pubmed publisher
    ..A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies. ..
  38. Thakur N, Tiwari V, Thomassin H, Pandey R, Kanduri M, Göndör A, et al. An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. Mol Cell Biol. 2004;24:7855-62 pubmed
    ..The unmethylated Kcnq1 ICR harbors bidirectional silencer activity and drives expression of an antisense RNA, Kcnq1ot1, which overlaps the Kcnq1 coding region...
  39. Saxena A, Carninci P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. Bioessays. 2011;33:830-9 pubmed publisher
    ..Finally, we point to future areas of research and put forward our recommendations for improvements in resources and applications of existing technologies towards targeted outcomes in this active area of research. ..
  40. Al Khtib M, Perret A, Khoueiry R, Ibala Romdhane S, Blachère T, Greze C, et al. Vitrification at the germinal vesicle stage does not affect the methylation profile of H19 and KCNQ1OT1 imprinting centers in human oocytes subsequently matured in vitro. Fertil Steril. 2011;95:1955-60 pubmed publisher
    ..Methylation profile of H19 and KCNQ1OT1 imprinting control regions, H19DMR and KvDMR1, respectively...
  41. Soejima H, Nakagawachi T, Zhao W, Higashimoto K, Urano T, Matsukura S, et al. Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer. Oncogene. 2004;23:4380-8 pubmed
    ..It has been, however, controversial whether the diminution is caused by imprinting disruption of the CDKN1C/LIT1 domain or by promoter hypermethylation of CDKN1C itself...
  42. Ma G, Chang S, Chang Y, Chang S, Yang C, Lee M, et al. Rapid prenatal confirmation of LIT1 hypomethylation using a novel quantitative method (E-Q-PCR) in fetuses with Beckwith-Wiedemann syndrome impressed with ultrasonography. Fertil Steril. 2008;90:1279-82 pubmed publisher
    We described a simplified and high-performance test (E-Q-PCR) for rapid assessment of the DNA methylation status at LIT1, a major genetic locus of Beckwith-Wiedemann syndrome (BWS)...
  43. Robbins K, Chen Z, WELLS K, Rivera R. Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and bovine. J Biomed Sci. 2012;19:95 pubmed publisher
    ..b>KCNQ1OT1 and PLAGL1 were paternally-expressed while CDKN1C and H19 were maternally-expressed in B. t. indicus x B. t...
  44. Tierling S, Souren N, Reither S, Zang K, Meng Hentschel J, Leitner D, et al. DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome. Clin Genet. 2011;79:546-53 pubmed publisher
    ..like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and ..
  45. Ren K, Xu R, Huang J, Zhao J, Shi W. Knockdown of long non-coding RNA KCNQ1OT1 depressed chemoresistance to paclitaxel in lung adenocarcinoma. Cancer Chemother Pharmacol. 2017;80:243-250 pubmed publisher
    ..Lung adenocarcinoma (LAD) is the main lung cancer class. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) gene is an lncRNA which had been reported high-expression in colorectal cancer...