ClinGen Dosage Sensitivity Curation Page

ACSL4

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11889465 Meloni (2002): This paper includes a family with three brothers with intellectual disability who had a sequence change (c.1003-2A>G) that reveals a cryptic splice site and results in a stop codon and truncated protein and reduced enzyme activity. The carrier mother was normal and had skewed X-inactivation. There is also a family with a missense mutation found in males with intellectual disability which was found to cause reduced enzyme activity. All carrier females are normal and have skewed X-inactivation.
12525535 Longo (2003): A family with a missense mutation found in males with intellectual disability that resulted in reduced enzyme activity. Carrier females were normal and had skewed X-inactivation.

Haploinsufficiency phenotype comments:

An additional family with a missense mutation is reported by Yonath et al (PMID: 21584729) and large deletions which include ACSL4, as well as other genes, have been reported in individuals with Alport syndrome and intellectual disability (PMIDs: 20186809, 9480748).

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.