UniProtKB/Swiss-Prot P46597: Variant p.Asn17Lys

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

17 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 Asparagine (N) to Lysine (K) at position 17 (N17K, p.Asn17Lys). 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 polar (N) to large size and basic (K) 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:

Nearly abolishes enzyme activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs17149149 [ dbSNP | Ensembl ]

Sequence information Variant position:

17 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:

MGSSEDQAYRLLNDYA N GFMVSQVLFAACELGVFDLL 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                         MGSSEDQAY-RLLNDYANGFMVSQVLFAACELGVFDLL

Rhesus macaque                MGSSGDDGY-RLLNEYTNGFMVSQVLFAACELGVFDL

Mouse                         ASARQERDF-RALMDLAHGFMASQVLFAGCALRVFDA

Rat                           REGELDRDF-RVLMSLAHGFMVSQVLFAALDLGIFDL

Bovine                        MCSQEGEGY-SLLKEYANGFMVSQVLFAACELGVFEL

Chicken                       MDSTEDLDYPQIIFQYSNGFLVSKVMFTACELGVFDL

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
Mutagenesis	11 – 11	L -> F. Reduced enzyme activity.
Mutagenesis	31 – 31	L -> H. No effect on enzyme activity.
Helix	7 – 31

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; 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; Sequencing ASMT identifies rare mutations in Chinese Han patients with autism.
Wang L.; Li J.; Ruan Y.; Lu T.; Liu C.; Jia M.; Yue W.; Liu J.; Bourgeron T.; Zhang D.;
PLoS ONE 8:E53727-E53727(2013)
Cited for: VARIANTS LYS-17; TRP-115; SER-151; ILE-166; GLY-179; MET-211; MET-217 AND LEU-243;

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.