Home  |  Contact
Due to maintenance work, this service will be unavailable Mon Feb 13 between 07:00 and 09:30 - CET. Apologies for the inconvenience.

UniProtKB/Swiss-Prot P32245: Variant p.Ile316Ser

Melanocortin receptor 4
Gene: MC4R
Variant information

Variant position:  316
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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

Variant description:  In obesity; shows reduced cAMP response to alpha-MSH; retains normal affinity for the antagonist AGRP.
Any additional useful information about the variant.

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



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.

TypePositionsDescription
Chain 1 – 332 Melanocortin receptor 4
Topological domain 305 – 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: VARIANTS OBESITY SER-62; ASP-97; PRO-106; LYS-125; GLN-165; THR-175; ILE-253; TYR-271 AND SER-316; CHARACTERIZATION OF VARIANTS OBESITY SER-62; ASP-97; PRO-106; LYS-125; GLN-165; THR-175; ILE-253; TYR-271 AND SER-316;

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;

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.