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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P47871: Variant p.Arg225His

Glucagon receptor
Gene: GCGR
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Variant information Variant position: help 225 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Histidine (H) at position 225 (R225H, p.Arg225His). 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: help Change from large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In MVAH; when associated in cis with M-368; decreased glucagon binding and decreased glucagon-elicited cAMP production; decreased localization to the cell membrane. Any additional useful information about the variant.


Sequence information Variant position: help 225 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 477 The length of the canonical sequence.
Location on the sequence: help KIGDDLSVSTWLSDGAVAGC R VAAVFMQYGIVANYCWLLVE 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KIGDDLSVSTWLSDGAVAGCRVAAVFMQYGIVANYCWLLVE

Mouse                         KIGDDLSVSVWLSDGAMAGCRVATVIMQYGIIANYCWLLVE

Rat                           KIGDDLSVSVWLSDGAVAGCRVATVIMQYGIIANYCWLLVE

Pig                           RLGDDLSVSIWLSDEAVAGCRVAAVFMQYGVVANYCWLLVE
Sequence annotation in neighborhood: help 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 26 – 477 Glucagon receptor
Topological domain 199 – 225 Extracellular
Disulfide bond 224 – 294
Mutagenesis 208 – 208 D -> Q. Abolishes glucagon binding.
Mutagenesis 209 – 209 D -> C. Causes the formation of an artifactual disulfide bond that abolishes glucagon binding; when associated with C-113.
Mutagenesis 210 – 210 L -> C. Causes the formation of an artifactual disulfide bond that interferes with glucagon binding; when associated with C-130.
Mutagenesis 215 – 215 W -> L. Abolishes glucagon binding.
Mutagenesis 232 – 232 Q -> L. Abolishes expression at cell surface and glucagon binding.
Mutagenesis 233 – 233 Y -> A. Abolishes glucagon binding. Strongly reduces expression at the cell surface.
Helix 218 – 253



Literature citations
Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations.
Sipos B.; Sperveslage J.; Anlauf M.; Hoffmeister M.; Henopp T.; Buch S.; Hampe J.; Weber A.; Hammel P.; Couvelard A.; Hoebling W.; Lieb W.; Boehm B.O.; Kloeppel G.;
J. Clin. Endocrinol. Metab. 100:E783-E788(2015)
Cited for: VARIANTS MVAH HIS-225 AND MET-368; INVOLVEMENT IN MVAH;
Characterization of a naturally occurring mutation V368M in the human glucagon receptor and its association with metabolic disorders.
Lin G.; Liu Q.; Dai A.; Cai X.; Zhou Q.; Wang X.; Chen Y.; Ye C.; Li J.; Yang D.; Wang M.W.;
Biochem. J. 477:2581-2594(2020)
Cited for: CHARACTERIZATION OF VARIANTS MVAH HIS-225 AND MET-368; VARIANTS SER-40; MET-76; GLN-336; HIS-414; ARG-416; GLN-428; LEU-438; HIS-458; VAL-461 AND LEU-476; CHARACTERIZATION OF VARIANTS SER-40; MET-76; GLN-336; HIS-414; ARG-416; GLN-428; LEU-438; HIS-458; VAL-461 AND LEU-476; FUNCTION; SUBCELLULAR LOCATION;
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.