UniProtKB/Swiss-Prot P32245: Variant p.Ile316Ser

Melanocortin receptor 4
Gene: MC4R
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Variant information Variant position:

316 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 Serine (S) at position 316 (I316S, p.Ile316Ser). 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 hydrophobic (I) to small size and polar (S) 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]. Additional information on the polymorphism described.
Variant description:

Risk factor for OBESITY; reduced cAMP response to alpha-MSH; normal affinity for the antagonist AGRP. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121913564 [ dbSNP | Ensembl ]

Sequence information Variant position:

316 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:

IIDPLIYALRSQELRKTFKE I ICCYPLGGLCDLSSRY 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                         IIDPLIYALRSQELRKTFKEIICC-YPLGGLCDLSSRY

Mouse                         VIDPLIYALRSQELRKTFKEIICF-YPLGGICELSSR

Rat                           VIDPLIYALRSQELRKTFKEIICF-YPLGGICELPGR

Pig                           IIDPLIYALRSQELRKTFKEIICC-YPLGGLCDLSSR

Bovine                        IIDPLIYALRSQELRKTFKEIICC-SPLGGLCDLSSR

Zebrafish                     VIDPLIYAFRSQEMRKTFKEICCCWYGLASLCV----

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
Topological domain	303 – 332	Cytoplasmic
Lipidation	318 – 318	S-palmitoyl cysteine

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;
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.