ClinGen Dosage Sensitivity Curation Page

SHROOM4

  • 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 have been no clear loss of function mutations or focal deletions reported for SHROOM4. Hagens et al. (2006, PMID:16249884) report two unrelated females who had intellectual disability, variable dysmorphic features, and other variable features who had apparently balanced X;autosome translocations that interrupted SHROOM4. However, both breakpoints within the autosomal regions either also disrupted a gene or were within a gene-rich region. Hagens also report a family with Stocco dos Santos XLMR syndrome (OMIM 300434) segregating with a missense mutation, but functional studies have not been done. The group also reported other sequence variants in patients with XLMR, some of which were also present in controls. Honda et al (2010, PMID: 20613765) report a male with moderate mental retardation and a 2.86 Mb deletion including SHROOM4 and many other genes.

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.