| *607807 | ||||||||
| ATP-BINDING CASSETTE, SUBFAMILY A, MEMBER 13; ABCA13 | ||||||||
| HGNC Approved Gene Symbol: ABCA13 | ||||||||
| Cytogenetic location: 7p12.3 Genomic coordinates (GRCh37): 7:48,211,056 - 48,687,090 (from NCBI) | ||||||||
| TEXT | ||||||||
| Description | ||||||||
| Members of the ATP-binding cassette (ABC) transporter superfamily carry out energy-dependent transport of substrate molecules. ABCA13 belongs to a subfamily of ABC transporters that contain 2 transmembrane (TM) domains, each with about 6 membrane-spanning segments, and 2 nucleotide-binding domains (NBDs), which are located in the cytoplasm. | ||||||||
| Cloning | ||||||||
| By screening sequence databases using conserved ABCA subfamily domains, followed by 3-prime and 5-prime RACE of a lung cDNA library, Prades et al. (2002) cloned full-length ABCA13. The deduced 5,058-amino acid protein contains an N-terminal signal sequence. The C-terminal half contains 2 sets of 6 TM helices and intracellular NBDs separated by a highly hydrophobic sequence. Prades et al. (2002) detected 5 splice variants that encode deduced proteins ranging in size from 2,654 to 4,958 amino acids. These alternative transcripts result in alternative C termini or the loss of a large N-terminal segment, including the signal peptide. Prades et al. (2002) also predicted a variant encoding a deduced 717-amino acid protein due to alternative splicing of exon 17. ABCA13 shares about 36% identity with several other ABCA transporters, with highest homology in the 2 ATP-binding domains. RT-PCR detected 2 alternatively spliced transcripts expressed at highest levels in trachea, testis, and bone marrow. PCR analysis of mouse tissues detected expression of Abca13 in kidney and skeletal muscle. The authors identified ESTs derived from mouse kidney and retina that contain Abca13. | ||||||||
| Gene Structure | ||||||||
| Prades et al. (2002) determined that the ABCA13 gene contains 62 exons and spans more than 450 kb. Exons 17 and 18 are large, containing 4,779 and 1,827 bp, respectively. | ||||||||
| Mapping | ||||||||
| By genomic sequence analysis, Prades et al. (2002) mapped the ABCA13 gene to chromosome 7p12.3. Using radiation hybrid analysis, they mapped the mouse Abca13 gene to chromosome 11A1 in a region that shows homology of synteny to human chromosome 7p12.3. | ||||||||
| Molecular Genetics | ||||||||
| Knight et al. (2009) reported evidence that ABCA13 is a susceptibility factor for both schizophrenia and bipolar disorder. After the initial discovery of its disruption by a chromosome abnormality in a person with schizophrenia, Knight et al. (2009) resequenced ABCA13 exons in 100 cases with schizophrenia and 100 controls. Multiple rare coding variants were identified including 1 nonsense and 9 missense mutations and compound heterozygosity/homozygosity in 6 cases. Variants were genotyped in more than 1,600 additional schizophrenia, bipolar, depression cases and in more than 950 control cohorts, and the frequency of all rare variants combined was greater than controls in schizophrenia (odds ratio = 1.93, P = 0.0057) and bipolar disorder (odds ratio = 2.71, P = 0.00007). The population-attributable risk of these mutations was 2.2% for schizophrenia and 4.0% for bipolar disorder. In a study of 21 families of mutation carriers, Knight et al. (2009) genotyped affected and unaffected relatives and found significant linkage (lod = 4.3) of rare variants with a phenotype including schizophrenia, bipolar disorder, and major depression. Knight et al. (2009) concluded that their data identified a candidate gene (ABCA13), highlighted the genetic overlap between schizophrenia, bipolar disorder, and depression, and suggested that rare coding variants may contribute significantly to risk of these disorders. | ||||||||
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