KCNQ1OT1

Summary

KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1, HGNC:6295) is a long non-coding RNA gene on chromosome 11p15.5.

Human chromosomal region 11p15.5 contains two clusters of epigenetically-regulated genes that are expressed from only one chromosome in a parent-of-origin manner. Each cluster, or imprinted domain, is regulated by a functionally independent imprinting control region (ICR). The human CDKN1C/KCNQ1OT1 domain is regulated by an ICR located in an intron of KCNQ1, and contains at least eight genes that are expressed exclusively or preferentially from the maternally-inherited allele. The DNA of the ICR is specifically methylated on the maternally-inherited chromosome, and unmethylated on the paternally-inherited chromosome. The ICR contains the promoter of the KCNQ1OT1 gene that is exclusively expressed from the paternal allele. The KCNQ1OT1 transcript is the antisense to the KCNQ1 gene and is a unspliced long non-coding RNA. It interacts with chromatin and regulates transcription of multiple target genes through epigenetic modifications. The transcript is abnormally expressed from both chromosomes in most patients with Beckwith-Wiedemann syndrome, and the transcript also plays an important role in colorectal carcinogenesis.

Source: NCBI Gene 10984 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6295
Approved symbol	KCNQ1OT1
Name	KCNQ1 opposite strand/antisense transcript 1
Location	11p15.5
Locus type	RNA, long non-coding
Status	Approved
Aliases	KvDMR1, KCNQ1-AS2, KvLQT1-AS, LIT1, NCRNA00012
Ensembl gene	ENSG00000269821
Ensembl biotype	lncRNA
OMIM	604115
Entrez	10984
RNAcentral	URS00000CE0D1 — lncRNA, 91667 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 lncRNA

ENST00000597346, ENST00000710656, ENST00000710657, ENST00000710658, ENST00000710659, ENST00000710661, ENST00000710662, ENST00000710663, ENST00000710664, ENST00000710665, ENST00000710673, ENST00000710674, ENST00000710675, ENST00000710676

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000597346 — 1 exons

Exon	Start	End
ENSE00004012792	2608328	2699994

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1980 / max 614.9040, expressed in 1480 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118237	9.1240	1479
118238	0.0740	21

Top tissues by expression

229 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	94.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.37	gold quality
kidney epithelium	UBERON:0004819	89.61	gold quality
left ventricle myocardium	UBERON:0006566	89.33	gold quality
tendon of biceps brachii	UBERON:0008188	82.73	gold quality
oviduct epithelium	UBERON:0004804	82.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.96	silver quality
sperm	CL:0000019	81.84	gold quality
germinal epithelium of ovary	UBERON:0001304	80.46	gold quality
superficial temporal artery	UBERON:0001614	80.05	gold quality
parietal pleura	UBERON:0002400	79.20	gold quality
nasal cavity epithelium	UBERON:0005384	78.51	gold quality
medial globus pallidus	UBERON:0002477	78.44	gold quality
visceral pleura	UBERON:0002401	78.21	gold quality
globus pallidus	UBERON:0001875	77.59	gold quality
pancreatic ductal cell	CL:0002079	77.40	silver quality
vena cava	UBERON:0004087	77.18	silver quality
upper arm skin	UBERON:0004263	77.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.88	silver quality
myocardium	UBERON:0002349	76.16	gold quality
inferior vagus X ganglion	UBERON:0005363	76.15	gold quality
cardia of stomach	UBERON:0001162	75.80	silver quality
caecum	UBERON:0001153	75.23	gold quality
pigmented layer of retina	UBERON:0001782	74.92	gold quality
gingival epithelium	UBERON:0001949	74.81	gold quality
subthalamic nucleus	UBERON:0001906	74.63	silver quality
epithelium of mammary gland	UBERON:0003244	74.33	gold quality
mammary duct	UBERON:0001765	74.25	gold quality
ventral tegmental area	UBERON:0002691	74.25	silver quality
layer of synovial tissue	UBERON:0007616	73.76	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	1126.88
E-CURD-119	yes	52.03
E-MTAB-9543	no	12414.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• KCNQ1OT1 gene encodes a non-protein coding, antisense RNA that is preferentially expressed from the paternal allele. (PMID:10369866)
• epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects (PMID:11813134)
• Hypomethylation of kcnq10t1 causes Beckwith-Weidemann syndrome (PMID:12136243)
• Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19 (PMID:12439823)
• In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene (PMID:12772698)
• An epimutation at KvDMR1, the absence of maternal methylation, causes the aberrant silencing of CDKN1C, some 180 kb away on the maternal chromosome. (PMID:14627666)
• Loss of CpG methylation was associated with loss of histone H3 lysine 9 (H3K9) methylation at DMR-LIT1. DMR-LIT1 epigenetically regulates CDKN1C expression not through histone modifications at CDKN1C promoter, but through that of DMR-LIT1. (PMID:15007390)
• promotor analysis for gene regulation (PMID:15233993)
• Deletion of the elements necessary for Kcnq1ot1 promoter function resulted in the loss of silencing activity. (PMID:15340049)
• KCNQ1OT1 is part of an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome. (PMID:15888726)
• LIT1, imprinted genes related to BWS, was expressed only in stages of 8-cell and blastocyst. (PMID:15952111)
• Recent advances in epigenetic control of the CDKN1C/KCNQ1OT1 imprinted domain in both humans and mice, causing Beckwith-Wiedemann syndrome and cancer. (review) (PMID:16575194)
• Maternal methylation imprints were already established at the germinal vesicle stageshowing that the KvDMR1 carries a germline methylation imprint. (PMID:16950814)
• Loss of imprinting of LIT1 and epigenetic status at the KvDMR1 is associated with colorectal cancers (PMID:16965397)
• KCNQ1OT1 can silence cyclin-dependent kinase inhibitor 1C (Cdkn1c) in transgenic mice by a mechanism independent of Kcnq1ot1 transcription. (PMID:18079696)
• 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). (PMID:18249379)
• A domain at the 5’ end of the Kcnq1ot1 RNA that carries out transcriptional silencing of linked genes using an episomal vector system was characterized. (PMID:18299392)
• Results suggests that hyperstimulation likely recruits young follicles that are unable to acquire imprint at KvDMR1 during the course of the maturing process. (PMID:18762571)
• Epimutations of the KCNQ1OT1 imprinting center of chromosome 11 in early human embryo lethality (PMID:19178079)
• Hypomethylation at KvDMR1 was observed in 3/18 clinically normal children conceived by ARTs (PMID:19494037)
• Data found biallelic expression of KCNQ10T1 gene in one induced pluripotent stem cell line. (PMID:19711451)
• exclusive correlation of the observed Beckwith-Wiedemann syndrome symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome (PMID:20618351)
• Vitrification at the germinal vesicle stage does not affect the methylation profile of H19 and KCNQ1OT1 imprinting centers in human oocytes. (PMID:21420679)
• KCNQ1OT1 RNA interacts with chromatin through its most 5’ 20 kb sequence in Beckwith-Wiedemann syndrome and Silver-Russell syndrome patients. (PMID:21920939)
• Hypermethylation of KvDMR1 was associated with developmental delay. (PMID:22300968)
• findings show that hypomethylation of the KCNQ1OT1 gene contributes to the occurrence of adrenocortical carcinoma and adenoma in patients without clear phenotypic features of the Beckwith-Wiedemann syndrome (PMID:22610651)
• Human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature during in vitro cell culture. H19 and KCNQ1OT1 possessed a substantial degree of hypermethylation status, and variable DNA methylation patterns of SNRPN was observed. (PMID:23040914)
• Based on these findings we conclude that the imprinted gene expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 are conserved between human and bovine (PMID:23153226)
• a tetranucleotide repeat polymorphism within KCNQ1OT1 contributes to hepatocellular carcinoma, possibly by affecting KCNQ1OT1 expression through a structure-dependent mechanism (PMID:23984860)
• In patients with Beckwith-Wiedemann syndrome due to hypomethylation of KvDMR1, the clinical presentation of Hyperinsulinemic hypoglycemia is quite heterogeneous with no correlation with the degree of KvDMR1 hypomethylation. (PMID:24468603)
• No evidence for copy number and methylation variation in H19 and KCNQ10T1 imprinting control regions in children born small for gestational age. (PMID:24934635)
• the cases with partial loss of methylation in KCNQ1OT1 and SNRPN present clinical features different to those associated with the corresponding imprinting syndromes (PMID:26106604)
• HOTAIR, H19 and KCNQ101T are confirmed as potential breast tumour markers demonstrable by in situ hybridization. (PMID:26323944)
• beta-catenin signaling may contribute to development of colorectal cancer by functioning as a novel Long noncoding RNAs regulatory factor via direct targeting of KCNQ1OT1. (PMID:26868975)
• The mean Beckwith-Wiedemann syndrome (BWS)score was 5.6 for 19 subjects with “IC2 hypomethylation”(KCNQ1OT1-associated ), compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1( H19-associated imprinting center) hypermethylation was 6 and 7, respectively (PMID:27436784)
• Analysis of the chromatin status of Cdkn1c promoter and KvDMR1 in unresponsive compared to responsive cell types showed that their differential responsiveness to the MyoD-dependent induction of the gene does not involve just their methylation status but, rather, the differential H3 lysine 9 dimethylation at KvDMR1. (PMID:27611768)
• Knockdown of KCNQ1OT1 expression significantly suppressed H2O2-induced SRA01/04 cell pyroptosis in vitro, which is the critical step in cataract formation. (PMID:28535504)
• lncRNA KCNQ1OT1 was highly expressed in lung adenocarcinoma (LAD) and functioned as a potential oncogene to inhibit malignancy and chemoresistance of LAD cells (PMID:28600629)
• Differential methylation/imprinting of KCNQ1OT1 is associated with the risk for symptomatic prolonged QTc. (PMID:28749187)
• findings showed that pathogenesis of selective intrauterine growth restriction may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta. (PMID:28803575)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.