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Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1
Author(s) -
Neville Matt J.,
Johnstone Elaine C.,
Walton Robert T.
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20039
Subject(s) - biology , genetics , restriction fragment length polymorphism , ankyrin repeat , gene , genotype
The dopamine D2 receptor has been extensively studied in relation to alcoholism, substance abuse, and nicotine dependence. The most frequently examined polymorphism linked to this gene is the Taq 1A restriction fragment length polymorphism (RFLP) (dbSNP rs1800497; g.32806C>T in GenBank AF050737.1), which has been associated with a reduction in D2 receptor density, although this is not universally accepted. The Taq 1A RFLP lies 10 kB downstream of DRD2 and may therefore fall within a different coding region than the DRD2 gene or within a regulatory region. Within this downstream region, we have identified a novel kinase gene, named ankyrin repeat and kinase domain containing 1 (ANKK1), which contains a single serine/threonine kinase domain and is expressed at low levels in placenta and whole spinal cord RNA. This gene is a member of an extensive family of proteins involved in signal transduction pathways. The DRD2 Taq 1A RFLP is a single nucleotide polymorphism (SNP) that causes an amino acid substitution within the 11th ankyrin repeat of ANKK1 (p.Glu713Lys), which, while unlikely to affect structural integrity, may affect substrate‐binding specificity. If this is the case, then changes in ANKK1 activity may provide an alternative explanation for previously described associations between the DRD2 Taq 1A RFLP and neuropsychiatric disorders such as addiction. Hum Mutat 23:540‐545, 2004. © 2004 Wiley‐Liss, Inc.