ORPHA: 2073; DO: 8986; MONDO: 0013639;
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38) : 19:6,900,001-12,600,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19p13.2 | Narcolepsy 6 | 614223 | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of narcolepsy, see 161400.
Kornum et al. (2011) reported genomewide association analyses for narcolepsy with replication and fine mapping across 3 ethnic groups (3,406 individuals of European ancestry, 2,414 Asians, and 302 African Americans) and identified a single-nucleotide polymorphism (SNP) in a 3-prime untranslated region of the purinergic receptor subtype P2Y11 gene (P2RY11) on chromosome 19p13.2 associated with narcolepsy (rs2305795, combined p = 6.1 x 10(-10), OR = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele was correlated with reduced expression of P2RY11 in CD8+ T lymphocytes (339% reduced, p = 0.003) and natural killer cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low-expression variant was also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (p = 0.0007) and natural killer cells (P = 0.001). Kornum et al. (2011) concluded that their results identified P2RY11 as an important regulator of immune cell survival, with possible implications in narcolepsy and other autoimmune diseases.
Kornum, B. R., Kawashima, M., Faraco, J., Lin, L., Rico, T. J., Hesselson, S., Axtell, R. C., Kuipers, H., Weiner, K., Hamacher, A., Kassack, M. U., Han, F., and 48 others. Common variants in P2RY11 are associated with narcolepsy. Nature Genet. 43: 66-71, 2011. Note: Erratum: Nature Genet. 43: 1040 only, 2011. [PubMed: 21170044] [Full Text: https://doi.org/10.1038/ng.734]