ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
24307393 Authors did whole genome and targeted sequencing in 9 patients with isolated intellectual disability (ID) of variable degrees without any copy number variations using SNP microarray. The 9 patients were selected from an initial cohort of 236 ID patients which had a medical record review and were determined to have isolated ID based on inclusion criteria set by authors. A de novo splice site mutation in trio 2 was identified suggesting that KDM5B may be a possible ID related candidate gene. No functional studies were performed.
28720891 Authors used whole exome sequencing in an attempt to identify risk genes or rare variants in a cohort of 19 proband-parent trios from singleton families with autism spectrum disorder from Saudi Arabia. Among the 19 probands, one proband (Patient 19) was found to have a de novo nonsense variant p.Y755X in the KDM5B gene. No functional studies were performed.
25363768 Whole exome sequencing of the Simons simplex collection including unaffected sibling and parent in each family was done. Results showed KDM5B as one of the recurrently mutated genes. Figure 2 and supplementary Table 2 showed a total of 4 de novo mutations in KDM5B identified in four ASD probands (2 likely gene disrupting and 2 missense) and 4 occurring in unaffected siblings (2 likely gene disrupting and 2 missense) . None of the 8 individuals appear to be related based on family ID in Table 2. No functional studies or further discussion on KDM5B was done.

Haploinsufficiency phenotype comments:

Additional PMID:28263302 identified a single de novo frame shift insertion (predicted to cause a loss of function,LOF) in a patient from an individual with autism spectrum disorder. PMID:25363760 performed whole exome sequencing on 15,480 DNA samples. Authors identified 1 de novo LOF variant and 1 missense variant , 4 inherited LOF variants, 19 inherited missense variants all in ASD patients. A total of 34 case-control cases were identified with KDM5B variants. Case-controls include 10 affected patients ( 1 LOF, 9 missense) and 24 unaffected (7 LOF, 17 missense). Due to the frequency of variants seen in controls a score of 1 has been given at this time.

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