UniProtKB/Swiss-Prot P32245: Variant p.Ile251Leu

Melanocortin receptor 4
Gene: MC4R
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Variant information Variant position:

251 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 Isoleucine (I) to Leucine (L) at position 251 (I251L, p.Ile251Leu). 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:

2 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 variations in MC4R define the body mass index quantitative trait locus 20 (BMIQ20) [MIM:618406]. MC4R loss-of-function variants are associated with higher body mass index, obesity, type 2 diabetes, and coronary artery disease. Gain-of-function variants have been reported to be associated with lower body mass index and resistance to obesity. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs52820871 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

GTGAIRQGANMKGAITLTIL I GVFVVCWAPFFLHLIFYISC 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                         GTGAIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISC

Mouse                         GTGTIRQGTNMKGAITLTILIGVFVVCWAPFFLHLLFYISC

Rat                           GTGTIRQGANMKGAITLTILIGVFVVCWAPFFLHLLFYISC

Pig                           GTGTIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISC

Bovine                        GSGTIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISC

Zebrafish                     GNGPIWQAANMKGAITITILLGVFVVCWAPFFLHLILMISC

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 – 332	Melanocortin receptor 4
Transmembrane	249 – 271	Helical; Name=6
Helix	241 – 270

Literature citations
Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.
Hinney A.; Schmidt A.; Nottebom K.; Heibult O.; Becker I.; Ziegler A.; Gerber G.; Sina M.; Gorg T.; Mayer H.; Siegfried W.; Fichter M.; Remschmidt H.; Hebebrand J.;
J. Clin. Endocrinol. Metab. 84:1483-1486(1999)
Cited for: VARIANTS OBESITY PHE-30; VAL-37; LEU-78; TRP-165; SER-252 AND THR-317; VARIANTS MET-112 AND LEU-251; Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children.
Dubern B.; Clement K.; Pelloux V.; Froguel P.; Girardet J.-P.; Guy-Grand B.; Tounian P.;
J. Pediatr. 139:204-209(2001)
Cited for: VARIANTS OBESITY MET-50; CYS-58; SER-102 AND VAL-170; VARIANTS ILE-103 AND LEU-251; Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.
Farooqi I.S.; Keogh J.M.; Yeo G.S.H.; Lank E.J.; Cheetham T.; O'Rahilly S.;
N. Engl. J. Med. 348:1085-1095(2003)
Cited for: VARIANTS OBESITY ALA-11; SER-62; ASP-97; LYS-125; GLN-165; THR-175; TYR-271; ARG-271 AND SER-316; VARIANTS ILE-103; MET-112 AND LEU-251; CHARACTERIZATION OF VARIANTS OBESITY ALA-11; SER-62; ASP-97; LYS-125; GLN-165; THR-175; TYR-271 AND SER-316; CHARACTERIZATION OF VARIANTS ILE-103; MET-112 AND LEU-251; FUNCTION; Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese Finnish children and adults.
Valli-Jaakola K.; Lipsanen-Nyman M.; Oksanen L.; Hollenberg A.N.; Kontula K.; Bjoerbaek C.; Schalin-Jaentti C.;
J. Clin. Endocrinol. Metab. 89:940-945(2004)
Cited for: VARIANT OBESITY LEU-127; VARIANTS ILE-103; MET-112; THR-226 AND LEU-251; CHARACTERIZATION OF VARIANT OBESITY LEU-127; CHARACTERIZATION OF VARIANTS MET-112 AND THR-226; Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity.
Larsen L.H.; Echwald S.M.; Soerensen T.I.A.; Andersen T.; Wulff B.S.; Pedersen O.;
J. Clin. Endocrinol. Metab. 90:219-224(2005)
Cited for: VARIANTS OBESITY TYR-36; THR-102; GLN-165; THR-175; ASP-181; VAL-219 AND PHE-325; VARIANTS ILE-103; MET-112 AND LEU-251; CHARACTERIZATION OF VARIANTS OBESITY TYR-36; THR-102; GLN-165; ASP-181; VAL-219 AND PHE-325;

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.