ClinGen Dosage Sensitivity Curation Page

KDM5C

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
15586325 Jensen et al. (2005) report 3 families with X-linked mental retardation (XLMR) in affected males and loss of function mutations in KDM5C (JARID1C), including a frameshift and two nonsense mutations. One of the nonsense mutations and the frameshift mutation were inherited from normal mothers. In the family with the other nonsense mutation, inheritance was not confirmed. This family also had an affected female sibling with the mutation and there was a distant history of consanguinity. The authors also report four males with XLMR with missense mutations. Transcripts were not detected with either of the nonsense mutations but were found with the frameshift.
18697827 Abidi et al. (2008) report two males with XLMR who have a frameshift mutation that was also present in their unaffected sister and mother. Skewed X-inactivation was shown for the sister and mother. They also report an adopted male with XLMR who had a c.1583+5G>A that produced abnormal transcripts and resulted in a frameshift and truncated protein.
19826449 Rujirabanjerd et al. (2010) report a family with three brothers with XLMR who had a frameshift mutation that was inherited from a mother with learning difficulties. The resulting transcript was not degraded. They also provide a review of previously reported mutations.

Haploinsufficiency phenotype comments:

Additional loss of function mutations have been reported in males with XLMR by Tzschach et al. (PMID:16541399) and Santos-Reboucas et al. (PMID: 21575681). Missense mutations that segregate with XLMR or autism have been reported as well (PMID: 16541399, 22326837, 16538222, 18203167).

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

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

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.