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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41220: Variant p.Ala99Gly

Regulator of G-protein signaling 2
Gene: RGS2
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Variant information Variant position: help 99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Alanine (A) to Glycine (G) at position 99 (A99G, p.Ala99Gly). 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 small size and hydrophobic (A) to glycine (G) 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 No effect on down-regulation of angiotensin-activated signaling pathway. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 99 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 211 The length of the canonical sequence.
Location on the sequence: help LWSEAFDELLASKYGLAAFR A FLKSEFCEENIEFWLACEDF 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                         LWSEAFDELLASKYGLAAFRAFLKSEFCEENIEFWLACEDF

Mouse                         LWAEAFDELLASKYGLAAFRAFLKSEFCEENIEFWLACEDF

Rat                           LWAEAFDELLASKYGLAAFRAFLKSEFCEENIEFWLACEDF

Pig                           LWAEAFDELLASKYGLAAFRAFLKSEFCEENIEFWLACEDF

Bovine                        LWSEAFDELLASKYGLAAFRAFLKSEFCEENIEFWLACEDF

Caenorhabditis elegans        GWSQSFENLMKHRAGQKYFAEFLKGEYSDENILFWQACEEL

Baker's yeast                 ---KGHHERMRSPYTIQKFYKFLKRAHCEENLEFFEKAHQF

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 1 – 211 Regulator of G-protein signaling 2
Domain 83 – 199 RGS
Region 79 – 116 Necessary to inhibit protein synthesis
Mutagenesis 79 – 79 L -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with E-86; L-87; S-90; K-102; F-105; I-110; E-111 and L-114.
Mutagenesis 86 – 86 E -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; L-87; S-90; K-102; F-105; I-110; E-111 and L-114.
Mutagenesis 87 – 87 L -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; S-90; K-102; F-105; I-110; E-111 and L-114.
Mutagenesis 90 – 90 S -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; L-87; K-102; F-105; I-110; E-111 and L-114.
Mutagenesis 102 – 102 K -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; L-87; S-90; F-105; I-110; E-111 and L-114.
Mutagenesis 105 – 105 F -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; L-87; S-90; K-102; I-110; E-111 and L-114.
Mutagenesis 106 – 106 C -> S. Changes specificity and confers GNAI1 binding; when associated with D-184. Strongly increases affinity for GNAI1 and GNAI3; when associated with D-184 and K-191.
Mutagenesis 110 – 110 I -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; L-87; S-90; K-102; F-105; E-111 and L-114.
Mutagenesis 111 – 111 E -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; L-87; S-90; K-102; F-105; I-110 and L-114.
Mutagenesis 114 – 114 L -> A. Near loss of EIF2B5 binding and inhibition of in vitro translation; when associated with L-79; E-86; L-87; S-90; K-102; F-105; I-110 and E-111.
Helix 91 – 103



Literature citations
Human missense mutations in regulator of G protein signaling 2 affect the protein function through multiple mechanisms.
Phan H.T.N.; Sjoegren B.; Neubig R.R.;
Mol. Pharmacol. 92:451-458(2017)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH GNAQ; CHARACTERIZATION OF VARIANTS ARG-2; LEU-2; GLY-3; VAL-4; VAL-5; ASN-18; ASP-23; TYR-40; HIS-44; LYS-50; LEU-55; HIS-78; GLY-99; VAL-110; HIS-188 AND ARG-196; Analysis of protein-coding genetic variation in 60,706 humans.
Lek M.; Karczewski K.J.; Minikel E.V.; Samocha K.E.; Banks E.; Fennell T.; O'Donnell-Luria A.H.; Ware J.S.; Hill A.J.; Cummings B.B.; Tukiainen T.; Birnbaum D.P.; Kosmicki J.A.; Duncan L.E.; Estrada K.; Zhao F.; Zou J.; Pierce-Hoffman E.; Berghout J.; Cooper D.N.; Deflaux N.; DePristo M.; Do R.; Flannick J.; Fromer M.; Gauthier L.; Goldstein J.; Gupta N.; Howrigan D.; Kiezun A.; Kurki M.I.; Moonshine A.L.; Natarajan P.; Orozco L.; Peloso G.M.; Poplin R.; Rivas M.A.; Ruano-Rubio V.; Rose S.A.; Ruderfer D.M.; Shakir K.; Stenson P.D.; Stevens C.; Thomas B.P.; Tiao G.; Tusie-Luna M.T.; Weisburd B.; Won H.H.; Yu D.; Altshuler D.M.; Ardissino D.; Boehnke M.; Danesh J.; Donnelly S.; Elosua R.; Florez J.C.; Gabriel S.B.; Getz G.; Glatt S.J.; Hultman C.M.; Kathiresan S.; Laakso M.; McCarroll S.; McCarthy M.I.; McGovern D.; McPherson R.; Neale B.M.; Palotie A.; Purcell S.M.; Saleheen D.; Scharf J.M.; Sklar P.; Sullivan P.F.; Tuomilehto J.; Tsuang M.T.; Watkins H.C.; Wilson J.G.; Daly M.J.; MacArthur D.G.;
Nature 536:285-291(2016)
Cited for: VARIANTS ARG-2; LEU-2; GLY-3; VAL-4; VAL-5; ASN-18; ASP-23; TYR-40; HIS-44; LYS-50; LEU-55; GLY-99; VAL-110; HIS-188 AND ARG-196;
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.