ClinGen Dosage Sensitivity Curation Page

RP2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
16969763 Pelletier et al. (2007) described several mutations identified amongst a French cohort with X-linked retinitis pigmentosa, including 4 previously unreported frameshifts and one previously unreported nonsense mutation. The group also identified one family with a whole gene deletion of RP2, though the extent of this deletion was not determined in this study.
9697692 Schwahn et al. (1998) identified two nonsense and two frameshift mutations amongst unrelated individuals with X-linked retinitis pigmentosa. These mutations were not identified amongst 92 controls.
10090907 Hardcastle et al. (1999) identified a nonsense mutation, R120X, in three apparently unrelated families with X-linked retinitis pigmentosa.

Haploinsufficiency phenotype comments:

Whole gene and intragenic deletions of RP2, as well as sequence-level mutations predicted to result in a loss-of-function cause X-linked retinitis pigmentosa (RP) (XLRP). While a verified focal RP2 deletion has not yet been reported, the vast majority of described RP2 mutations are truncating, and non-focal RP2 deletions have been reported [PMID 16419135, 16385466, 22126752]. Typically female carriers of RP2 mutations are asymptomatic; PMIDs 15031171 and 16969763 report affected females with heterozygous frameshift RP2 mutation and a 2-bp RP2 deletion/t(X;A), respectively.

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.