- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
This report describes occipital horn syndrome (OHS), one of several diseases associated with the human ATP7A gene; OHS exhibits sex-linked recessive inheritance. ATP7A encodes Cu(2+)-transporting ATPase, alpha polypeptide, a transmembrane copper-transporting P-type ATPase. There is one high-scoring ortholog in Drosophila, ATP7, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated. ATP7A is associated with several other diseases, neuronopathy, distal hereditary motor, X-linked (MIM:300489, FBhh0000078) and Menkes disease (MIM:309400, FBhh0000076). Dmel\ATP7 is also orthologous to a paralogous gene in human, ATP7B.
Multiple UAS constructs of the human Hsap\ATP7A gene have been introduced into flies, including wild-type and a variant implicated in disease (see FBhh0000438). ATP7B has not been introduced into flies.
A variant analogous to one specifically implicated in OHS has been characterized in flies and been shown to act like a partial loss-of-function mutation. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): S536G in the fly ATP7 gene (corresponds to S833G in the human ATP7A gene). See the 'Disease-Implicated Variants' table below.
See the human disease model report for copper metabolism disorders, ATP7-related (FBhh0000438) for additional information on experimental results using Drosophila models of this and related diseases.
[updated Feb. 2024 by FlyBase; FBrf0222196]
[OCCIPITAL HORN SYNDROME; OHS](https://omim.org/entry/304150)
[ATPase, Cu(2+)-TRANSPORTING, ALPHA POLYPEPTIDE; ATP7A](https://omim.org/entry/300011)
Occipital horn syndrome is a disorder of copper transport caused by mutations in the copper-transporting ATPase gene (ATP7A). Occipital horn syndrome is characterized by "occipital horns," distinctive wedge-shaped calcifications at the sites of attachment of the trapezius muscle and the sternocleidomastoid muscle to the occipital bone. Occipital horns may be clinically palpable or observed on skull radiographs. Individuals with OHS also have lax skin and joints, bladder diverticula, inguinal hernias, and vascular tortuosity. Intellect is normal or slightly reduced. [from GeneReviews, ATP7A-Related Copper Transport Disorders, pubmed:20301586 2015.12.18]
Occipital horn syndrome is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. The disorder is sometimes accompanied by mild neurologic impairment, and bony abnormalities of the occiput are a common feature, giving rise to the name (summary by Das et al., 1995, pubmed:7887410). [From MIM:304150, 2015.12.18]
Occipital horn syndrome (OHS) is caused by recessive mutation in ATP7A. [From MIM:304150, 2015.12.18]
Similar abnormalities of copper and collagen metabolism were fouind in the cultured fibroblasts of 13 patients with Menkes syndrome (MIM:309400) and 2 patients with OHS (then called EDS IX). In both disorders, fibroblasts had markedly increased copper content and rate of incorporation of (64)Cu, and accumulation was in metallothionein or a metallothionein-like protein as previously established for Menkes cells. Histochemical staining showed that copper was distributed uniformly throughout the cytoplasm in both cell types, this location being consistent with accumulation in metallothionein. Both fibroblast types showed very low lysyl oxidase activity and increased extractability of newly synthesized collagen, but no abnormality in cell viability, duplication rate, prolyl 4-hydroxylase activity, or collagen synthesis rate. Skin biopsy specimens from one EDS IX patient showed the same abnormalities in lysyl oxidase activity and collagen extractability. Fibroblasts of the mother of EDS IX patients showed increased (64)Cu incorporation (Peltonen, et al., 1983, pubmed:6140952). [From MIM:304150, 2015.12.18]
The ATP7A gene encodes a transmembrane copper-transporting P-type ATPase, Cu(2+)-transporting ATPase, alpha polypeptide. P-type ATPases are a family of integral membrane proteins that use an aspartylphosphate intermediate to transport cations across membranes. The 1,500-residue ATP7A protein was found to have the characteristics of a copper-binding protein. It has 6 N-terminal copper binding sites and a catalytic transduction core with several functional domains (Vulpe et al., 1993, pubmed:8490659). [From MIM:300011 and MIM:304150, 2015.12.18]
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of human genes ATP7A and ATP7B (1 Drosophila to 2 human). Dmel\ATP7 shares 46-47% identity and 62% similarity with human genes.