Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Binding Sites
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Biological Clocks / genetics*
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Casein Kinases
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Chromosome Mapping
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Chromosomes, Human, Pair 2 / genetics
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Circadian Rhythm / genetics*
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Exons
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Female
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Genetic Linkage
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Glycine
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Humans
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Male
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Molecular Sequence Data
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Mutation, Missense
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Pedigree
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Period Circadian Proteins
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Phosphorylation
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Polymorphism, Single-Stranded Conformational
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Protein Kinases / metabolism
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Proteins / chemistry
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Proteins / genetics*
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Proteins / metabolism*
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Serine
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Sleep Disorders, Circadian Rhythm / genetics*
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Sleep Disorders, Circadian Rhythm / physiopathology
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Transcription Factors
Substances
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Nuclear Proteins
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PER2 protein, human
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Period Circadian Proteins
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Proteins
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Transcription Factors
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Serine
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Protein Kinases
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Casein Kinases
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Glycine