UniProtKB/Swiss-Prot Q9UGI9: Variant p.Arg446Met

5'-AMP-activated protein kinase subunit gamma-3
Gene: PRKAG3
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Variant information Variant position:

446 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 Arginine (R) to Methionine (M) at position 446 (R446M, p.Arg446Met). 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 large size and basic (R) to medium size and hydrophobic (M) 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:

Genetic variation in PRKAG3 defines the skeletal muscle glycogen content and metabolism quantitative trait locus (SMGMQTL) [MIM:619030]. Muscle fibers from carriers of variant Trp-225 have approximately 90% more muscle glycogen content than controls and decreased levels of intramuscular triglyceride. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs200750014 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LCLEGVLSCQPHESLGEVID R IAREQVHRLVLVDETQHLLG 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                         LCLEGVLSCQPHESLGEVIDRIAREQVHRLVLVDETQHLLG

Mouse                         LCLEGVLSCQPHESLGEVIDRIAREQVHRLVLVDETQHLLG

Pig                           LCLEGVLSCQPHETLGEVIDRIVREQVHRLVLVDETQHLLG

Bovine                        LCLEGVLSCQPHETLGEVIDRIAREQVHRLVLVDETQHLLG

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 – 489	5'-AMP-activated protein kinase subunit gamma-3
Domain	427 – 486	CBS 4
Binding site	432 – 432
Binding site	432 – 432
Binding site	432 – 432
Binding site	453 – 453

Literature citations
Gain-of-function R225W mutation in human AMPKgamma(3) causing increased glycogen and decreased triglyceride in skeletal muscle.
Costford S.R.; Kavaslar N.; Ahituv N.; Chaudhry S.N.; Schackwitz W.S.; Dent R.; Pennacchio L.A.; McPherson R.; Harper M.E.;
PLoS ONE 2:E903-E903(2007)
Cited for: VARIANTS ALA-71; GLN-76; GLY-103; VAL-113; VAL-153; PRO-161; SER-171; SER-180; THR-197; GLN-211; GLN-225; TRP-225; ARG-260; THR-269; CYS-307; GLN-340; TRP-340; MET-446; VAL-482 AND ASN-485; INVOLVEMENT IN SMGMQTL; FUNCTION; CHARACTERIZATION OF VARIANT TRP-225;

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.