UniProtKB/Swiss-Prot P32245: Variant p.Ala175Thr

Melanocortin receptor 4
Gene: MC4R
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Variant information Variant position:

175 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 Alanine (A) to Threonine (T) at position 175 (A175T, p.Ala175Thr). 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 small size and hydrophobic (A) to medium size and polar (T) 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
Polymorphism:

Genetic variations in MC4R define the body mass index quantitative trait locus 20 (BMIQ20) [MIM:618406]. Additional information on the polymorphism described.
Variant description:

Risk factor for OBESITY; partial cAMP response to alpha-MSH. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121913563 [ dbSNP | Ensembl ]

Sequence information Variant position:

175 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:

LQYHNIMTVKRVGIIISCIW A ACTVSGILFIIYSDSSAVII 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                         LQYHNIMTVKRVGIIISCIWAACTVSGILFIIYSDSSAVII

Mouse                         LQYHNIMTVRRVGIIISCIWAACTVSGVLFIIYSDSSAVII

Rat                           LQYHNIMTVRRVGIIISCIWAACTVSGVLFIIYSDSSAVII

Pig                           LQYHNIMTVKRVGIIISCIWAVCTVSGVLFIIYSDSSAVII

Bovine                        LQYHNIMTVKRVAITISAIWAACTVSGVLFIIYSDSSAVII

Zebrafish                     LRYHNIMTQRRAGTIITCIWTFCTVSGVLFIVYSESTTVLI

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	167 – 188	Helical; Name=4
Disulfide bond	40 – 279
Helix	163 – 186

Literature citations
Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms.
Yeo G.S.H.; Lank E.J.; Farooqi I.S.; Keogh J.; Challis B.G.; O'Rahilly S.;
Hum. Mol. Genet. 12:561-574(2003)
Cited for: INVOLVEMENT IN OBESITY; VARIANTS SER-62; ASP-97; PRO-106; LYS-125; GLN-165; THR-175; ILE-253; TYR-271 AND SER-316; CHARACTERIZATION OF VARIANTS SER-62; ASP-97; PRO-106; LYS-125; GLN-165; THR-175; ILE-253; TYR-271 AND SER-316; FUNCTION;
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: INVOLVEMENT IN OBESITY; VARIANTS ALA-11; SER-62; ASP-97; ILE-103; MET-112; LYS-125; GLN-165; THR-175; LEU-251; TYR-271; ARG-271 AND SER-316; CHARACTERIZATION OF VARIANTS ALA-11; SER-62; ASP-97; ILE-103; MET-112; LYS-125; GLN-165; THR-175; LEU-251; TYR-271 AND SER-316; FUNCTION;
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: INVOLVEMENT IN OBESITY; VARIANTS TYR-36; THR-102; ILE-103; MET-112; GLN-165; THR-175; ASP-181; VAL-219; LEU-251 AND PHE-325; CHARACTERIZATION OF VARIANTS TYR-36; THR-102; GLN-165; ASP-181; VAL-219 AND PHE-325;
Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk.
Zorn S.; Bounds R.; Williamson A.; Lawler K.; Hanssen R.; Keogh J.; Henning E.; Smith M.; Fielding B.A.; Umpleby A.M.; Yasmeen S.; Marti-Solano M.; Langenberg C.; Wabitsch M.; Collet T.H.; Farooqi I.S.;
Nat. Med. 0:0-0(2025)
Cited for: INVOLVEMENT IN OBESITY; PROTECTION FROM CARDIOVASCULAR DISEASE; VARIANTS ALA-11; GLY-19; 21-TYR--TYR-332 DEL; PHE-30; ALA-34; 35-TYR--TYR-332 DEL; VAL-37; LYS-42; ILE-53; PRO-54; ASP-55; VAL-55; GLY-61; LYS-61; SER-62; VAL-68; ARG-69; THR-69; ASP-70; SER-72; ARG-76; LEU-77; 80-TYR--TYR-332 DEL; CYS-80; 84-CYS--TYR-332 DEL; 88-VAL--LEU-92 DEL; LYS-91; PRO-92; ALA-95; ILE-95; ASP-97; ASN-102; PRO-106; MET-112; TYR-122; LYS-125; GLU-126; LEU-127; ARG-131; PHE-136; PRO-136; THR-137; ARG-139; HIS-141; ASN-143; SER-144; GLY-146; ILE-150; PRO-156; MET-160; THR-161; ILE-162; GLN-165; TRP-165; ILE-166; ILE-170 DEL; VAL-170; 174-TRP--TYR-332 DEL; THR-175; PHE-177; PRO-180; THR-191; MET-200 DEL; VAL-200; LEU-202; ARG-204; PRO-211; ARG-215; THR-227; SER-232; CYS-236; ASP-238; SER-240; ASN-246; GLN-250; SER-252; ILE-253; 258-TRP--TYR-332 DEL; GLN-260; THR-260; PRO-263; ASN-269; ARG-271; TYR-271; LEU-272; PRO-273; SER-274; 276-TYR--TYR-332 DEL; LEU-284; 287-TYR--TYR-332 DEL; 295-SER--TYR-332 DEL; HIS-299; LEU-299; PRO-300; VAL-301; THR-303; TRP-305; ASN-306; 307-GLN--TYR-332 DEL; LYS-308; GLU-314; SER-316 AND LYS-331;

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.