UniProtKB/Swiss-Prot P46597: Variant p.Leu298Phe

Acetylserotonin O-methyltransferase
Gene: ASMT
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Variant information Variant position:

298 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Leucine (L) to Phenylalanine (F) at position 298 (L298F, p.Leu298Phe). 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 (L) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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
Variant description:

Found in patients with neuropsychiatric disorders; uncertain significance; nearly abolishes enzyme activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121918822 [ dbSNP | Ensembl ]

Sequence information Variant position:

298 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

345 The length of the canonical sequence.
Location on the sequence:

GILVIESLLDEDRRGPLLTQ L YSLNMLVQTEGQERTPTHYH 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.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GILVIESLLDEDRRGPLLTQLYSLNMLVQTEGQERTPTHYH

Rhesus macaque                GILVIESLLDEDRRGPLLTQLYSLNMLVQTEGQERTPTHYH

Mouse                         AVLLVESVLSPGGAGPTRTLLLSLTMLLQARGRERTEAEYR

Rat                           ALLLVEAVLAKGGAGPLRSLLLSLNMMLQAEGWERQASDYR

Bovine                        GILVIESLLDTDGRGPLTTLLYSLNMLVQTEGRERTPAEYR

Chicken                       GVLLVESLLSEDRSGPVETQLYSLNMLVQTEGKERTAVEYS

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 – 345	Acetylserotonin O-methyltransferase
Binding site	302 – 302
Binding site	306 – 306
Mutagenesis	296 – 296	T -> M. Nearly abolishes enzyme activity.
Mutagenesis	318 – 318	H -> D. Reduced enzyme activity.
Helix	294 – 305

Literature citations
Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway.
Botros H.G.; Legrand P.; Pagan C.; Bondet V.; Weber P.; Ben-Abdallah M.; Lemiere N.; Huguet G.; Bellalou J.; Maronde E.; Beguin P.; Haouz A.; Shepard W.; Bourgeron T.;
J. Pineal Res. 54:46-57(2013)
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEXES WITH S-ADENOSYL-L-METHIONINE; N-ACETYL SEROTONIN AND ZINC IONS; CATALYTIC ACTIVITY; FUNCTION; ACTIVE SITE; CHARACTERIZATION OF ISOFORMS 1; 2 AND 3; SUBUNIT; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS HIS-13; LYS-17; GLN-61; GLU-81; MET-171; GLY-210; ARG-219; LEU-243; MET-269; SER-273; ALA-278; ASP-288; GLN-291; PHE-298 AND MET-305; MUTAGENESIS OF LEU-11; ARG-111; TYR-248; THR-296 AND HIS-318; Is ASMT a susceptibility gene for autism spectrum disorders? A replication study in European populations.
Toma C.; Rossi M.; Sousa I.; Blasi F.; Bacchelli E.; Alen R.; Vanhala R.; Monaco A.P.; Jarvela I.; Maestrini E.;
Mol. Psychiatry 12:977-979(2007)
Cited for: VARIANTS ASP-288 AND PHE-298; Abnormal melatonin synthesis in autism spectrum disorders.
Melke J.; Goubran Botros H.; Chaste P.; Betancur C.; Nygren G.; Anckarsater H.; Rastam M.; Stahlberg O.; Gillberg I.C.; Delorme R.; Chabane N.; Mouren-Simeoni M.C.; Fauchereau F.; Durand C.M.; Chevalier F.; Drouot X.; Collet C.; Launay J.M.; Leboyer M.; Gillberg C.; Bourgeron T.;
Mol. Psychiatry 13:90-98(2008)
Cited for: VARIANTS LYS-17; GLU-81; ALA-278 AND PHE-298; Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with intellectual disability.
Pagan C.; Botros H.G.; Poirier K.; Dumaine A.; Jamain S.; Moreno S.; de Brouwer A.; Van Esch H.; Delorme R.; Launay J.M.; Tzschach A.; Kalscheuer V.; Lacombe D.; Briault S.; Laumonnier F.; Raynaud M.; van Bon B.W.; Willemsen M.H.; Leboyer M.; Chelly J.; Bourgeron T.;
BMC Med. Genet. 12:17-17(2011)
Cited for: VARIANTS HIS-13; LYS-17; GLN-61; MET-171; GLY-210; ARG-219; LEU-243; SER-273; ASP-288; GLN-291 AND PHE-298; Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.
Chaste P.; Clement N.; Botros H.G.; Guillaume J.L.; Konyukh M.; Pagan C.; Scheid I.; Nygren G.; Anckarsater H.; Rastam M.; Stahlberg O.; Gillberg I.C.; Melke J.; Delorme R.; Leblond C.; Toro R.; Huguet G.; Fauchereau F.; Durand C.; Boudarene L.; Serrano E.; Lemiere N.; Launay J.M.; Leboyer M.; Jockers R.; Gillberg C.; Bourgeron T.;
J. Pineal Res. 51:394-399(2011)
Cited for: VARIANTS GLY-210 AND PHE-298; Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder.
Etain B.; Dumaine A.; Bellivier F.; Pagan C.; Francelle L.; Goubran-Botros H.; Moreno S.; Deshommes J.; Moustafa K.; Le Dudal K.; Mathieu F.; Henry C.; Kahn J.P.; Launay J.M.; Muhleisen T.W.; Cichon S.; Bourgeron T.; Leboyer M.; Jamain S.;
Hum. Mol. Genet. 21:4030-4037(2012)
Cited for: VARIANTS GLN-61; ARG-219; LEU-243; SER-273; ASP-288; GLN-291; PHE-298 AND MET-305;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.