ClinGen Dosage Sensitivity Curation Page

ZNF674

  • 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
16385466 Lugtenberg et al (2006) identified a male patient with learning disabilities, retinal dystrophy, and short stature who was shown by X-chromosomal BAC array analysis to carry a deletion of approximately 1 Mb in Xp11.3, including ZNF674 and four other genes. Subsequent screening of the ZNF674 gene in 28 XLID families and 309 index patients with previous family history suggestive of X-linked inheritance resulted in the identification of a nonsense and two missense mutations in three patients, respectively. The nonsense mutation (p.E118X) was shown to fully segregate with the phenotype, with all carrier females showing skewed X-inactivation patterns. Of the two missense mutations one (p.T343M) appeared to be a polymorphism and the other (p.P412L) could not be confirmed as causative.

Haploinsufficiency phenotype comments:

PMID:22126752 Delphin et al. (2012) reported a series a nine male individuals from two separate families segragating a retinal dystrophy phenotype with a deletion including ZNF674, RP2 (thought to be causative of the retinal dystrophy phenotype) and several other genes. All individuals were reported to have normal psychomotor development since birth. The deletions in these two families were distinct from each other as well as previously reported deletions involving ZNF674.

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:

PMID 20691945: Ramaswamy et al reported a female patient with intellectual disability in whom the duplication of two genes, ZNF673 and ZNF674, was identified by microarray analysis. The origin of the duplication could not be determined.

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.