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Mendeliome

Gene: KCNQ1OT1

Amber List (moderate evidence)

KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1 (non-protein coding))
EnsemblGeneIds (GRCh38): ENSG00000269821
EnsemblGeneIds (GRCh37): ENSG00000269821
OMIM: 604115, Gene2Phenotype
KCNQ1OT1 is in 4 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Limited evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Expression is increased in BWS due to IC2 epimutations or paternal UPD.

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Sources: Expert Review
Created: 17 Oct 2021, 6:12 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)

Phenotypes
Beckwith-Wiedemann syndrome OMIM:130650; Russell-Silver Syndrome

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Sources
  • Expert Review Amber
  • Expert Review
Phenotypes
  • Beckwith-Wiedemann syndrome OMIM:130650
  • Russell-Silver Syndrome
OMIM
604115
Clinvar variants
Variants in KCNQ1OT1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

11 Mar 2025, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).

17 Oct 2021, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kcnq1ot1 has been classified as Red List (Low Evidence).

17 Oct 2021, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: KCNQ1OT1 was added gene: KCNQ1OT1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: KCNQ1OT1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 23511928; 30794780; 29377879; 10220444; 32447323; 33177595; 29047350 Phenotypes for gene: KCNQ1OT1 were set to Beckwith-Wiedemann syndrome OMIM:130650; Russell-Silver Syndrome Review for gene: KCNQ1OT1 was set to AMBER