ClinGen Dosage Sensitivity Curation Page

ATP6AP2

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)

Haploinsufficiency phenotype comments:

From DGV, Bentley et al. (PMID 18987734) and McKernan et al. (PMID 19546169) report on the same male individual with a small intronic deletion within ATP6AP2 identified by whole genome sequencing. Also of note: Ramser et al. (2005) identified a silent mutation in an exonic splicing enhancer site, resulting in exon skipping, in seven males in one family. These individuals had intellectual and developmental disability as well as general tonic-clonic seizures (PMID: 15746149). However, it appears that the exon skipped is in-frame, and the resulting protein is still largely functional. While there are many caveats to the usefulness of this finding and its translatability to human phenotypes, we felt it was useful to point out that Amsterdam et al (2004), PMID 15256591, reported large rearrangements of ATP6AP2 as embryologically lethal in zebrafish.

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.