ClinGen Dosage Sensitivity Curation Page

NXF5

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
11566096 Jun et al. (2001) report a male patient with a syndromic form of intellectual disability and inv(X)(p21.1;q22). The breakpoint at Xq22 interrupts NXF5 and the authors demonstrated absent mRNA levels.

Haploinsufficiency phenotype comments:

Frints et al (2003) provide additional clinical details on the patient reported by Jun (PMID: 11566096) and screened 115 male patients with syndromic or non-syndromic X-linked intellectual disability for mutations. They found 4 sequence changes (including two silent changes and one intronic change) that were either found in control populations or did not segregate with the condition in the family; none were considered causative (PMID:12784308). Other reports of large deletions or other rearrangements include PMIDs: 20096387, 20338563, and 22030050. While NXF5 has been proposed as a candidate gene for intellectual disability and premature ovarian failure, there have not been any focal deletions or loss of function mutations reported.

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:

Froyen et al. (2007) report a 0.8 Mb duplication that includes NXF5 and 14 other genes in a boy with intellectual disability. The duplication was found in his normal mother, who had skewed X-inactivation, and his maternal uncle who had intellectual disability. There have been no reports of focal duplications of NXF5 alone.

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.