ClinGen Dosage Sensitivity Curation Page

SRPX2

  • 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 two reports of missense mutations in patients with rolandic epilepsy, mental retardation, and speech dyspraxia (OMIM 300643). A N327S mutation was found in a large family with both males and females affected and results in a gain of N-glycosylation and increased protein retention in the endoplasmic reticulum. A Y72S mutation was identified in a male patient with rolandic seizures who also had bilateral perisylvian polymicrogyria and was present in his mother and maternal aunt, who were normal, and two other maternal aunts who had mild intellectual disability (PMID: 16497722). Royer-Zemmour et al (2008) showed that the Y72S mutation leads to gain of affinity for binding partner uPAR (PMID: 18718938). While loss of function has not been ruled out as a disease mechanism, a dominant-negative effect or other gain of function remain possible mechanisms. Furthermore, two female patients with idiopathic epilepsy (a phenotype that is distinct from rolandic epilepsy) have been described with genomic deletions that include SRPX2. The PCDH19 gene was involved for both patients and considered causative, but the lack of rolandic seizures and speech dyspraxia in these patients may suggest that haploinsufficiency of SRPX2 does not lead to the rolandic epilepsy phenotype (PMIDs: 22091964 and 21053371).

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.