An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.
Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are "morning larks" with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (hPer2), a human homolog of the period gene in Drosophila, maps to the same locus. Affected individuals have a serine to glycine mutation within the casein kinase Iepsilon (CKIepsilon) binding region of hPER2, which causes hypophosphorylation by CKIepsilon in vitro. Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period.
Toh
K L
KL
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Jones
C R
CR
He
Y
Y
Eide
E J
EJ
Hinz
W A
WA
Virshup
D M
DM
Ptácek
L J
LJ
Fu
Y H
YH
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D001683:Biological Clocks / Q000235:genetics*; D047388:Casein Kinases; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005998:Glycine; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D056950:Period Circadian Proteins; D010766:Phosphorylation; D018807:Polymorphism, Single-Stranded Conformational; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012694:Serine; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors
D009687:Nuclear Proteins; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D011506:Proteins; D014157:Transcription Factors; D012694:Serine; D011494:Protein Kinases; D047388:Casein Kinases; D005998:Glycine