UniProtKB/Swiss-Prot P01112: Variant p.Gln22Lys

GTPase HRas
Gene: HRAS
Chromosomal location: 11p15.5
Variant information

Variant position:  22
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 Glutamine (Q) to Lysine (K) at position 22 (Q22K, p.Gln22Lys).
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 polar (Q) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  Congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]: Variant of Costello syndrome. {ECO:0000269|PubMed:17412879}. 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 CMEMS.
Any additional useful information about the variant.

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



Sequence information

Variant position:  22
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  189
The length of the canonical sequence.

Location on the sequence:   TEYKLVVVGAGGVGKSALTI  Q LIQNHFVDEYDPTIEDSYRK
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                         TEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRK

Mouse                         TEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRK

Rat                           TEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRK

Chicken                       TEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRK

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 – 186 GTPase HRas
Chain 2 – 186 GTPase HRas, N-terminally processed
Modified residue 2 – 2 N-acetylthreonine; in GTPase HRas, N-terminally processed
Mutagenesis 17 – 17 S -> N. Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane. No effect on subcellular location of isoform 2.
Mutagenesis 26 – 26 N -> G. Loss of interaction with PLCE1; when associated with V-12.
Mutagenesis 29 – 29 V -> A. No effect on interaction with PLCE1; when associated with V-12.
Mutagenesis 32 – 32 Y -> F. Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12.
Mutagenesis 34 – 34 P -> G. No effect on interaction with PLCE1; when associated with V-12.
Mutagenesis 35 – 35 T -> S. Loss of interaction with PLCE1; when associated with V-12.
Mutagenesis 37 – 37 E -> G. No effect on interaction with PLCE1; when associated with V-12.
Mutagenesis 38 – 38 D -> N. No effect on interaction with PLCE1; when associated with V-12.
Mutagenesis 39 – 39 S -> C. No effect on interaction with PLCE1; when associated with V-12.
Helix 16 – 25


Literature citations

Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation.
van der Burgt I.; Kupsky W.; Stassou S.; Nadroo A.; Barroso C.; Diem A.; Kratz C.P.; Dvorsky R.; Ahmadian M.R.; Zenker M.;
J. Med. Genet. 44:459-462(2007)
Cited for: VARIANTS CMEMS VAL-12; SER-12; LYS-22 AND LYS-63;

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.