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  3. KDM6B
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Early onset or syndromic epilepsy

Gene: KDM6B

Green List (high evidence)
KDM6B (lysine demethylase 6B)
EnsemblGeneIds (GRCh38): ENSG00000132510
EnsemblGeneIds (GRCh37): ENSG00000132510
OMIM: 611577, Gene2Phenotype
KDM6B is in 4 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Created: 2 May 2024, 1:13 p.m. | Last Modified: 6 May 2024, 9:20 p.m.
Panel Version: 5.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 2 May 2024, 1:13 p.m.
Last Modified: 6 May 2024, 9:20 p.m.
Panel version: 5.6

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

KDM6B variants have been associated with relevant phenotype in OMIM and as strong Gen2Phen gene for KDM6B-related developmental disorder (monoallelic). PMID: 37196654 reports that in their cohort, 9/69 (13%) of individuals had seizures.
Created: 6 Jul 2023, 9:27 a.m. | Last Modified: 6 Jul 2023, 9:27 a.m.
Panel Version: 4.67
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 6 Jul 2023, 9:21 a.m. | Last Modified: 6 Jul 2023, 9:21 a.m.
Panel Version: 4.67
Created: 6 Jul 2023, 9:21 a.m.
Last Modified: 6 Jul 2023, 9:21 a.m.
Panel version: 4.67

Hannah Robinson (South West Genomic Laboratory Hub)

Green List (high evidence)

Information from Rots et al. 2023 (PMID:37196654): According to OMIM, heterozygous variants in KDM6B cause “neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities.” Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.).

In this cohort, 9/69 (13%) of individuals had seizures.

The majority of individuals had de novo variants but 9/85 individuals inherited the variant (five maternal, four paternal) from a mildly affected (developmental delay [DD], learning problems, autism spectrum disorder [ASD]) or clinically unaffected parent.
Sources: NHS GMS
Created: 28 Jun 2023, 7:12 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 28 Jun 2023, 7:12 a.m.

Panel version: 4.62

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505
  • neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790
OMIM
611577
Clinvar variants
Variants in KDM6B
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

2 May 2024, Gel status: 3

Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: KDM6B.

2 May 2024, Gel status: 3

Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to KDM6B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

6 Jul 2023, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: kdm6b has been classified as Amber List (Moderate Evidence).

6 Jul 2023, Gel status: 0

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_23_promote_green tag was added to gene: KDM6B.

6 Jul 2023, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: KDM6B were changed from Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505; neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790

6 Jul 2023, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: KDM6B were set to PMID: 37196654

28 Jun 2023, Gel status: 0

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

Hannah Robinson (South West Genomic Laboratory Hub)

gene: KDM6B was added gene: KDM6B was added to Early onset or syndromic epilepsy. Sources: NHS GMS Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM6B were set to PMID: 37196654 Phenotypes for gene: KDM6B were set to Global developmental delay; Intellectual disability; Hypotonia; Joint hypermobility; seizures; Overgrowth Penetrance for gene: KDM6B were set to Incomplete Review for gene: KDM6B was set to GREEN gene: KDM6B was marked as current diagnostic