ClinGen Dosage Sensitivity Curation Page

ARHGEF6

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

There are no clear loss of function mutations reported for ARHGEF6. One paper (PMID: 11017088) reports a boy with intellectual disability who has an apparently balanced t(X;21) that has a breakpoint within intron 10 of ARHGEF6. The mother is a carrier and phenotypically normal, so it would be expected that her normal X is inactivated. However, normal mRNA was detected in the mother and ARHGEF6 does not escape X-inactivation. This paper also reports a family with X-linked intellectual disability and an intronic substitution (IVS1-11T>C). This appeared to cause skipping of exon 2 yielding an in-frame deletion in a subset of transcripts. It is not clear if this single exon deletion would lead to loss-of-function of this gene.

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

Triplosensitivity phenotype comment:

Focal duplications of ARHGEF6 have not been reported. Larger duplications including ARHGEF6 and other genes have been reported (PMID: 20861843).

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.