ClinGen Dosage Sensitivity Curation Page

KDM6B

  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25363768 Iossifov et al. (2014) identified four unrelated males with autism spectrum disorder (ASD) who harbored de novo sequence variants in KDM6B. Whole exome sequencing identified a splice-site and frame-shift variant in two unrelated males with autism spectrum disorder. Sample ID: 11329 (Supplementary Table 2) harbored a spice-site variant (Chr17:7749188A>G, c.138-2A>G) while sample ID: 12683 (Supplementary Table 2) harbored a frame-shift variant (Chr17:7749921CG>C, c.575del). Neither of these variants were observed in gnomAD as of November 2018. Of note, sample ID: 12683 was reported previously in Iossifov et al. (2012; PMID: 22542183). Two additional de novo variants were observed in an additional two unrelated males with autism spectrum disorder. Sample ID: 13675 (Supplementary Table 2) harbored a 3 base pair synonymous deletion (17:7755287ACTT>A, c.4185_4187del) while sample ID: 13446 (Supplementary Table 2) harbored a single base pair intron substitution (17:7755659G>C, c.4468+5G>C). Neither of these variants were observed in gnomAD as of November 2018.

Haploinsufficiency phenotype comments:

25363760: De Rubeis et al. (2015) identified a de novo missense variant in the KDM6B gene (Chr17:7755277G>A, c.4174G>A, E1392K) in an individual with autism spectrum disorder (ASD) through whole exome sequencing (Supplementary Table 3). Within this study cohort no other variants in KDM6B were observed in any of the other 3,870 autism cases or in any of the 9,937 ancestry-matched or parental controls. 27479843: Lelieveld et al. (2016) identified, through whole exome sequencing three unrelated individuals with intellectual disability (ID) who harbored de novo sequence variants in KDM6B. Patient 159 harbored a missense variant (NM_001080424.1:c.32G>A, p.R11H), patient 340 harbored a missense variant (NM_001080424.1:c.4696C>A, p.R1566S), and patient 507 harbored a synonymous variant (NM_001080424.1:c.3825C>A, p.T1275T) (Supplementary Table 3). None of these variants were observed in gnomAD as of November 2018. Of note, of the three de novo variants only one variant (patient 340) was confirmed by Sanger sequencing. 28263302: Yuen et al. (2017) identified an individual (sample AU4427301) with autism spectrum disorder (ASD) who harbored a nonsense variant in the KDM6B gene (NM_001080424:c.343C>T, p.Q115X; Supplementary Table 5). This variant was identified through whole exome sequencing. It's unclear if the variant was de novo or inherited. This variant was not observed in gnomAD as of November 2018. 28097321: Reuter et al. (2017) reported two male sibling probands from a consanguineous relationship that harbored a six base pair deletion in the KDM6B gene (NM_001080424.1:c.1668_1673del, p.Asn557_ Ser558del) (family MR208, Supplementary table 1). These individuals presented with severe intellectual disability, mental deterioration, seizures, sleep disturbances, aggressive behavior, abnormalities of the face, cerebral atrophy, and hypoplasia of the corpus callosum.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity