The report describes a model that allows characterization of disease-implicated variants associated with the human genes FLVCR2 and FLVCR1. Most residues mutated in FLVCR1 and FLVCR2 in the context of disease are conserved in the Drosophila histamine transporter HisT, suggesting that these sites may play critical roles in substrate transport.
FLVCR2 is implicated in proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH); PVHH exhibits autosomal recessive inheritance. FLVCR2 encodes a protein that acts as an importer of heme and as a transporter for a calcium-chelator complex. A mutation of HisT analogous to the disease-implicated variant FLVCR2:p.Pro280Arg has been characterized in flies; see the 'Disease-Implicated Variants' table below.
A UAS construct of the human gene Hsap\FLVCR2 has been introduced into flies, but has not been characterized; a stock is available.
[updated Nov. 2022 by FlyBase; FBrf0222196]
[PROLIFERATIVE VASCULOPATHY AND HYDRANENCEPHALY-HYDROCEPHALY SYNDROME; PVHH](https://omim.org/entry/225790)
[FLVCR HEME TRANSPORTER 2; FLVCR2](https://omim.org/entry/610865)
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome is a rare usually prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. It is usually diagnosed by ultrasound between 26 and 33 weeks' gestation (summary by Meyer et al., 2010; pubmed:20206334). Rarely, affected individuals may survive, but are severely impaired with almost no neurologic development (Kvarnung et al., 2016; pubmed:25677735). [from MIM:225790; 2022.11.20]
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as encephaloclastic proliferative vasculopathy, is caused by homozygous or compound heterozygous mutation in the FLVCR2 gene. [from MIM:225790; 2022.11.20]
FLVCR2 encodes a transmembrane protein of the major facilitator superfamily; acts as an importer of heme and as a transporter for a calcium-chelator complex, which is important for growth and calcium metabolism. [GeneCards, FLVCR2; 2022.11.20]
Many to one: 2 human genes to 1 Drosophila gene.
High-scoring ortholog of human FLVCR2 and FLVCR1 (1 Drosophila to 2 human).
