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UniProtKB/Swiss-Prot P27986: Variant p.Arg649Trp

Phosphatidylinositol 3-kinase regulatory subunit alpha
Gene: PIK3R1
Variant information

Variant position:  649
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 Arginine (R) to Tryptophan (W) at position 649 (R649W, p.Arg649Trp).
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 large size and basic (R) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  SHORT syndrome (SHORTS) [MIM:269880]: A rare, multisystem disease characterized by short stature, anomalies of the anterior chamber of the eye, characteristic facial features such as triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, partial lipodystrophy, hernias, hyperextensibility, and delayed dentition. The clinical phenotype can include insulin resistance, nephrocalcinosis, and hearing deficits. Developmental milestones and cognition are normal. {ECO:0000269|PubMed:23810378, ECO:0000269|PubMed:23810379, ECO:0000269|PubMed:23810382}. 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 SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling.
Any additional useful information about the variant.

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

Sequence information

Variant position:  649
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  724
The length of the canonical sequence.

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.

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.

Chain 2 – 724 Phosphatidylinositol 3-kinase regulatory subunit alpha
Domain 624 – 718 SH2 2
Beta strand 645 – 650

Literature citations

Mutations in PIK3R1 cause SHORT syndrome.
Dyment D.A.; Smith A.C.; Alcantara D.; Schwartzentruber J.A.; Basel-Vanagaite L.; Curry C.J.; Temple I.K.; Reardon W.; Mansour S.; Haq M.R.; Gilbert R.; Lehmann O.J.; Vanstone M.R.; Beaulieu C.L.; Majewski J.; Bulman D.E.; O'Driscoll M.; Boycott K.M.; Innes A.M.; Friedman J.; Michaud J.; Bernier F.; Brudno M.; Fernandez B.; Knoppers B.; Samuels M.; Scherer S.;
Am. J. Hum. Genet. 93:158-166(2013)

SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling.
Chudasama K.K.; Winnay J.; Johansson S.; Claudi T.; Konig R.; Haldorsen I.; Johansson B.; Woo J.R.; Aarskog D.; Sagen J.V.; Kahn C.R.; Molven A.; Njolstad P.R.;
Am. J. Hum. Genet. 93:150-157(2013)
Cited for: VARIANT SHORTS TRP-649;

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.