KCNQ1OT1

  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KCNQ1OT1 (HGNC:6295) HGNC Entrez Ensembl OMIM UCSC GeneReviews LOVD LSDB ClinVar
HGNC Name
KCNQ1 opposite strand/antisense transcript 1
Gene type
non-coding RNA
Locus type
RNA, long non-coding
Previous symbols
No previous names found
Alias symbols
KvDMR1, KCNQ1-AS2, KvLQT1-AS, LIT1, NCRNA00012
%HI
0(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
Cytoband
11p15.5
Genomic Coordinates
GRCh37/hg19: chr11:2629558-2721228 NCBI Ensembl UCSC
GRCh38/hg38: chr11:2608328-2699994 NCBI Ensembl UCSC

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-32158
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
12/06/2023

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 33177595
    Mio et al. (2021) report a 1.4 kb paternally-inherited deletion of promoter and 5’ end of KCNQ1OT1 in a female proband with mild Silver-Russell syndrome, intrauterine growth restriction, facial dysmorphisms, and precocious puberty. Her father carried the same deletion on his maternally-inherited allele and was considered unaffected. The carrier paternal grandmother was also considered unaffected (parent of origin was not determined).
  • PUBMED: 32447323
    Eggerman et al. (2021) report a 132 bp paternally-inherited deletion within exon 1 of KCNQ1OT1 (intron 11 of KCNQ1) in a male proband with short stature and a history of being small for gestational age. His father carried the same deletion on his maternally-inherited allele and was considered unaffected. The carrier paternal grandmother was considered unaffected but showed short stature (parent of origin was not determined).
  • PUBMED: 35772847
    Gaudet et al. (2023) report a 132 bp paternally-inherited deletion within exon 1 of KCNQ1OT1 (intron 11 of KCNQ1) in a male proband with short stature and a history of being small for gestational age. Postnatal examination was consistent with Silver-Russell syndrome with a Netchine-Harbinson clinical score of 5 out of 6. Phenotypes included intrauterine and postnatal growth retardation, motor delay, speech delay, attention deficit hyperactivity disorder, oppositional defiance disorder, learning disability, hypoglycemic episodes, feeding difficulties, excessive sweating, prominent facial dysmorphisms (triangular face, frontal bossing, micrognathia, high nasal bridge and long eye lashes). His father carried the same deletion on his maternally-inherited allele and was considered unaffected. The carrier paternal grandmother was also considered unaffected (parent of origin was not determined) [Please note this case is not the same individual reported by Eggerman et al. (2021)].
  • PUBMED: 35772845
    Stoltze et al. (2023) report a 132 bp maternally-inherited deletion within exon 1 of KCNQ1OT1 (intron 11 of KCNQ1) in a female proband with desmoid fibromatosis and slight features of Beckwith Weidemann syndrome. Her mother carried the same deletion on her paternally-inherited allele and was considered unaffected.
  • PUBMED: 35906012
    Hana-Isono et al. (2022) report a de novo 5 kb deletion of the paternal allele of KCNQ1OT1 (intron 11 of KCNQ1) in a female proband with severe postnatal growth restrictions (height and weight), triangular face and normal psychomotor development. A Netchine-Harbison score of 3 out of 6 was reported for this patient. Hana-Isono et al. also report a de novo 12 kb deletion of the paternal allele of KCNQ1OT1 (intron 11 of KCNQ1) in a male proband with intrauterine and postnatal growth restriction (height, weight and head circumference), mild psychomotor delay, and fifth finger clinodactyly. A Netchine-Harbison score of 3 out of 6 was reported for this patient. Quantitative RT-PCR of patient cell lines showed a 5 fold increase in CDKN1C expression compared to controls, but expression of KCNQ1OT1 and KCNQ1 could not be assessed due to low expression in leucocytes.
HI Evidence Comments:
KCNQ1OT1 is an antisense transcript that encodes a single exon long non-coding RNA (lncRNA). It does not encode a protein product. It lies within a region known as imprinting center 2 (IC2), which is subject to differential methylation and parent of origin effects. KCNQ1OT1 is typically methylated on the maternal allele and thus only expressed from the paternal allele. The KCNQ1OT1 lncRNA acts to repress expression of CDKN1C from the paternal allele. Please note: a single exon of KCNQ1 (exon 11) is encoded on the opposite DNA strand within the sequence of KCNQ1OT1, so consideration should be given to copy number variants also impacting KCNQ1. Please see the separate ClinGen review for KCNQ1. Cases with deletion of KCNQ1OT1 suggest that loss of the maternal allele is associated with a Beckwith Weidemann-like syndromic presentation, while loss of the paternal allele is associated with a Silver Russell-like syndromic presentation. Reduced penetrance and variable expressivity have been noted as many carrier family members have been considered to be unaffected or subclinically affected. Additional literature describing cases that also include one or more exons of KCNQ1 (not counted as evidence toward HI score for KCNQ1OT1): PMID: 15372379; Niemitz et al. (2004) report a maternally-inherited 250 kb deletion of KCNQ1OT1 and most of KCNQ1 (intron 1 through somewhere between exon 11-14) in a family with three affected siblings: a 6 year-old male with Beckwith-Wiedemann syndrome (hemihypertrophy, hypospadias, cleft palate, midline abdominal wall defect, ear pits and creases, and macroglossia), a deceased female with prenatal overgrowth, ear creases and pits, and macroglossia, and a stillborn male with prenatal overgrowth and macroglossia. The mother carried the deletion on her paternal allele and was considered unaffected. Functional studies of the 6 year-old male showed normal expression of KCNQ1OT1 consistent with loss of the maternal allele, but decreased CDKN1C (p57KIP2) expression, while the carrier mother had no expression of KCNQ1OT1 consistent with loss of her paternal allele, but normal CDKN1C expression. PMID: 22205991; Algars et al. (2011) report a three generation family with Beckwith Wiedemann syndrome in the context of a maternally-inherited ~330 kb deletion of KCNQ1OT1 and most of KCNQ1 (minimum exons 2-11). Functional and clinical studies showed reduced CDKN1C expression with deletion of the maternal allele together with the BWS phenotype, while normal expression of CDKN1C was shown with deletion of the paternal allele with a normal phenotype. PMID:23511928; Gurrieri et al. (2013) reported a maternally-inherited 198kb deletion of KCNQ1OT1 and KCNQ1 exons 11-16 in a female proband with Beckwith Weidemann syndrome. The carrier mother (parent of origin not determined) was healthy with short stature. PMID:23243085; De Crescenzo et al. (2013) reported two fetuses with a paternally-inherited 60 kb deletion of the 5’ end of KCNQ1OT1 (40 kb) and exon 11 of KCNQ1. Both fetuses showed severe intrauterine growth restriction and fetal demise at 27 weeks gestation. At autopsy, no malformations were noted. PMID: 27374371; Cytrynbaum et al. (2016) reported a de novo 164 kb deletion of the paternal allele of KCNQ1OT1 and exons 11-15 of KCNQ1 in a female proband. Phenotypes included Silver-Russell syndrome with intrauterine growth restriction, postnatal growth restriction (height, weight and head circumference), ventricular septal defect, speech delay, hypoglycemia and facial dysmorphism (triangular face, pointy chin and downturned mouth). PMID: 21920939; Chisea et al. (2012) reported a maternally-inherited 160 kb inverted tandem duplication containing KCNQ1 exons 12-15 and the most 5’ 20kb of KCNQ1OT1. Phenotype was reported to be Beckwith Weidemann syndrome in proband and four additional family members when maternally transmitted. PMID: 21780245; Demars et al. (2011) reported a 50kb maternally-inherited duplication (chr11:2485000-2533000 [hg18]) of exon 2 of KCNQ1, which lies upstream of KCNQ1OT1 in a male proband with a clinical diagnosis of Beckwith Weidemann syndrome. His carrier mother and two maternal carrier aunts (parent of origin not determined) were considered unaffected.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Isolated, full gene gains of KCNQ1OT1 have not been reported in the medical literature to the best of our knowledge. Larger gains containing KCNQ1OT1 and other contiguous genes suggest that gain of the maternal allele may be associated with a Silver Russell-like syndromic presentation, while gain of the paternal allele is not currently known to be associated with a syndromic presentation. The clinically significant gene(s) and/or mechanisms of action responsible for any phenotypic differences have not been clearly identified and thus cannot be attributed specifically to KCNQ1OT1, and therefore the triplosensitivity score for the GENE is 0. Please see the curated regions for 11p15 for additional information.

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)