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UniProtKB/Swiss-Prot P46597: Variant p.Pro243Leu

Acetylserotonin O-methyltransferase
Gene: ASMT
Variant information

Variant position:  243
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 Leucine (L) at position 243 (P243L, p.Pro243Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Reduced enzyme activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  243
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:   SFQEEEQIDFQEGDFFKDPL  P EADLYILARVLHDWADGKCS
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                         SFQ-----EEEQIDFQEGDFFKDPLPEADLYILARVLHDWADGKCS

Rhesus macaque                SFP-----EEEEIHLQEGDFFKDPLPEADLYILARILHDWA

Mouse                         PPPADEDGAEPRVRFLSGDFFRSPLPPADLYVLARVLHDWA

Rat                           LSP----GARPSVRFVAGDFFRSRLPRADLFILARVLHDWA

Bovine                        SAS-----EDERISFHEGDFFKDALPEADLYILARVLHDWT

Chicken                       VPP-----EERRIAFHEGDFFKDSIPEADLYILSKILHDWD

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.

TypePositionsDescription
Chain 1 – 345 Acetylserotonin O-methyltransferase
Active site 255 – 255 Proton donor/acceptor
Binding site 252 – 252 S-adenosyl-L-methionine
Binding site 256 – 256 Substrate
Mutagenesis 248 – 248 Y -> H. Nearly abolishes enzyme activity.


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;

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 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;

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.