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UniProtKB/Swiss-Prot P09471: Variant p.Gly40Arg

Guanine nucleotide-binding protein G(o) subunit alpha
Gene: GNAO1
Chromosomal location: 16q13
Variant information

Variant position:  40
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glycine (G) to Arginine (R) at position 40 (G40R, p.Gly40Arg).
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 glycine (G) to large size and basic (R)
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

Involvement in disease:  Neurodevelopmental disorder with involuntary movements (NEDIM) [MIM:617493]: A neurodevelopmental disorder manifesting with a wide range of clinical symptoms. Clinical features range from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior and epileptic encephalopathy, to a milder phenotype featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia, and mild epilepsy. Hyperkinetic movements are often exacerbated by specific triggers, such as illness, emotion and high ambient temperature. Some patients have brain abnormalities, such as cerebral atrophy or thin corpus callosum. {ECO:0000269|PubMed:25966631, ECO:0000269|PubMed:26060304, ECO:0000269|PubMed:27068059, ECO:0000269|PubMed:27625011, ECO:0000269|PubMed:28357411}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:  Epileptic encephalopathy, early infantile, 17 (EIEE17) [MIM:615473]: A severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements. {ECO:0000269|PubMed:23993195, ECO:0000269|PubMed:25966631, ECO:0000269|PubMed:26485252, ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In EIEE17 and NEDIM.
Any additional useful information about the variant.

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



Sequence information

Variant position:  40
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  354
The length of the canonical sequence.

Location on the sequence:   EKNLKEDGISAAKDVKLLLL  G AGESGKSTIVKQMKIIHEDG
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                         EKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG

Mouse                         EKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG

Rat                           EKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG

Bovine                        EKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG

Xenopus laevis                EKNLKEDGVTAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG

Caenorhabditis elegans        EKNLKEDGMQAAKDIKLLLLGAGESGKSTIVKQMKIIHESG

Drosophila                    ERNLKEDGIQAAKDIKLLLLGAGESGKSTIVKQMKIIHESG

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 2 – 354 Guanine nucleotide-binding protein G(o) subunit alpha
Domain 32 – 354 G-alpha
Nucleotide binding 40 – 47 GTP
Region 35 – 48 G1 motif
Metal binding 47 – 47 Magnesium
Beta strand 34 – 40


Literature citations

Clinical whole-exome sequencing reveals a novel missense pathogenic variant of GNAO1 in a patient with infantile-onset epilepsy.
Law C.Y.; Chang S.T.; Cho S.Y.; Yau E.K.; Ng G.S.; Fong N.C.; Lam C.W.;
Clin. Chim. Acta 451:292-296(2015)
Cited for: VARIANT EIEE17 ARG-40;

GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome.
Danti F.R.; Galosi S.; Romani M.; Montomoli M.; Carss K.J.; Raymond F.L.; Parrini E.; Bianchini C.; McShane T.; Dale R.C.; Mohammad S.S.; Shah U.; Mahant N.; Ng J.; McTague A.; Samanta R.; Vadlamani G.; Valente E.M.; Leuzzi V.; Kurian M.A.; Guerrini R.;
Neurol. Genet. 3:E143-E143(2017)
Cited for: VARIANTS NEDIM ARG-40; GLY-47; THR-56; CYS-209 AND GLY-246;

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.