This report describes intellectual disability, X-linked 63; an alternative designation of this disease is 'mental retardation, X-linked 63' (MRX63), which is one of the series of diseases classified as intellectual disability, X-linked, nonsyndromic. Carrier females exhibit variable, milder cognitive disabilities. The human gene implicated in this disease is ACSL4, a long chain acyl-CoA synthetase, which is involved in the synthesis of complex lipids and degradation of fatty acids. There is a second related human gene, ACSL3. There is a single orthologous gene in Drosophila, Dmel\Acsl, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the human Hsap\ACSL4 gene have been introduced into flies. Heterologous rescue (functional complementation) of amorphic phenotypes of Dmel\Acsl has been demonstrated (FBrf0209077, FBrf0212968).
Amorphic and loss-of-function mutations of Dmel\Acsl are lethal when homozygous; some alleles survive to late larval stages, allowing phenotypic assessment. Neuroanatomy-defective and neurophysiology-defective phenotypes are observed. Physical interactions of the Dmel\Acsl protein product have been described; see below and in the FlyBase gene report for Acsl.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 63; XLID63](https://omim.org/entry/300387)
[ACYL-CoA SYNTHETASE LONG CHAIN FAMILY, MEMBER 4; ACSL4](https://omim.org/entry/300157)
Affected males show nonprogressive mental retardation ranging from severe to moderate, without seizures, whereas carrier females show highly variable cognitive capacities, ranging from moderate mental retardation to normal intelligence. [from MIM:300387; 2016.01.19]
Nonsyndromic X-linked mental retardation 63 is associated with mutations in the gene ACSL4. [from MIM:300387; 2016.01.19]
ACSL4 is a long chain acyl-CoA synthetase (LACS), enzymes which convert free long chain fatty acids into fatty acyl-CoA esters and are key intermediates in the synthesis of complex lipids. [from MIM:300157; 2016.01.19]
Many to one: 2 human to 1 Drosophila. Two human genes, ACSL3 and ACSL4, are orthologous to the fly gene Dmel\Acsl.
Ortholog of human genes ACSL3 and ACSL4 (1 Drosophila to 2 human). Dmel\Acsl shares 47-49% identity and 63-64% similarity with the human genes.
