ClinGen Dosage Sensitivity Curation Page

ZNF81

  • 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:

PMID15121780: Kleefstra et al. (2004) characterized the breakpoints of a de novo translocation, t(X;9)(p11.23;q34.3), in a female patient with severe mental retardation and found that the translocation disrupted the ZNF81 gene. No ZNF81 transcript was found in a lymphoblastoid cell line derived from the patient?s blood. The breakpoint on chromosome 9 involved the EU-HMTase gene. Kleefstra et al. (2004) then looked for other mutations of ZNF81 in 300 families and patients with nonspecific X-linked mental retardation. In one family, they found a ser179-to-asn substitution in ZNF81. The mutation fully segregated with the phenotype and was not observed in control samples.

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:

PMID22634100: Alesi et al. (2012) described a 3-year-old boy with developmental delay, autistic features and growth and speech delay. Array-CGH analysis detected a microduplication on the X chromosome (Xp11.2p11.3), spanning 335.4 kb and including ZNF81, ZNF182 and SPACA5. No duplications of the single gene, ZNF81, have been identified to date. PMID20662849: El-Hattab et al. (2011) found a ~1.3 Mb tandem duplication at Xp11.23p11.3 in an 11-year-old boy with ID and dysmorphic features. The duplicated region contained FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over-expression of genes in the interval may have contributed to the observed phenotype.

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.