UniProtKB/Swiss-Prot P56645: Variant p.Pro414Ala

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 414 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Proline (P) to Alanine (A) at position 414 (P414A, p.Pro414Ala). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: Change from medium size and hydrophobic (P) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

• Lowest score: -4 (low probability of substitution).
• Highest score: 11 (high probability of substitution).

More information can be found on the following page
Polymorphism: The number of repeats of 18 amino acids in positions 966 to 1055 is polymorphic and varies among at least 2 different alleles. Alleles corresponding in size to a 4 (PER3.4) and 5 (PER3.5) repeats have been described. The sequence shown is that of allele PER3.5. In most populations around 10% of individuals are homozygous for the 5-repeat (PER3.5), whereas approximately 50% are homozygous for the 4-repeat (PER3.4). In some populations in Papua New Guinea the prevalence of the various genotypes appears to be reversed. These repeats and polymorphism are not present in non-primate mammals. Homozygosity for PER3.5 is more likely to show morning preference, whereas homozygosity for the PER3.4 associates with evening preferences. PER3.5 homozygous show vulnerability to sleep loss with a greater cognitive decline in response to total sleep deprivation (PubMed:11306557, PubMed:17346965, PubMed:19716732, PubMed:24439663, PubMed:24577121). Additional information on the polymorphism described.
Other resources: Links to websites of interest for the variant.

• Variant rs150812083 [ dbSNP | Ensembl ]

Sequence information

Variant position: 414 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 1201 The length of the canonical sequence.
Location on the sequence: NDNDKDITELQEQIYKLLLQ P VHVSVSSGYGSLGSSGSQEQ The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

• Type: the type of sequence feature.
• Positions: endpoints of the sequence feature.
• Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 1201	Period circadian protein homolog 3

Literature citations

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.
Zhang L.; Hirano A.; Hsu P.K.; Jones C.R.; Sakai N.; Okuro M.; McMahon T.; Yamazaki M.; Xu Y.; Saigoh N.; Saigoh K.; Lin S.T.; Kaasik K.; Nishino S.; Ptacek L.J.; Fu Y.H.;
Proc. Natl. Acad. Sci. U.S.A. 113:E1536-E1544(2016)
Cited for: INVOLVEMENT IN FASPS3; VARIANT FASPS3 414-PRO--HIS-416 DELINS ALA-VAL-ARG; VARIANTS ALA-414 AND ARG-416; CHARACTERIZATION OF VARIANT FASPS3 414-PRO--HIS-416 DELINS ALA-VAL-ARG; FUNCTION; SUBCELLULAR LOCATION;