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UniProtKB/Swiss-Prot P01112: Variant p.Gly12Val

GTPase HRas
Gene: HRAS
Variant information Variant position: help 12 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Glycine (G) to Valine (V) at position 12 (G12V, p.Gly12Val). 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 glycine (G) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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

Variant description: help In CSTLO, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.

Sequence information Variant position: help 12 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 189 The length of the canonical sequence.
Location on the sequence: help MTEYKLVVVGA G GVGKSALTIQLIQNHFVDEY 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.




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.
Chain 1 – 186 GTPase HRas
Initiator methionine 1 – 1 Removed; alternate
Chain 2 – 186 GTPase HRas, N-terminally processed
Modified residue 1 – 1 N-acetylmethionine; in GTPase HRas; alternate
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.
Beta strand 12 – 15

Literature citations
Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras.
Song C.; Hu C.-D.; Masago M.; Kariya K.; Yamawaki-Kataoka Y.; Shibatohge M.; Wu D.; Satoh T.; Kataoka T.;
J. Biol. Chem. 276:2752-2757(2001)
Cited for: INTERACTION WITH PLCE1; CHARACTERIZATION OF VARIANT VAL-12; MUTAGENESIS OF SER-17; ASN-26; VAL-29; TYR-32; PRO-34; THR-35; GLU-37; ASP-38 AND SER-39; Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease.
Liu F.; Iqbal K.; Grundke-Iqbal I.; Rossie S.; Gong C.X.;
J. Biol. Chem. 280:1790-1796(2005)
Cited for: CHARACTERIZATION OF CSTLO VARIANT VAL-12; Germline mutations in HRAS proto-oncogene cause Costello syndrome.
Aoki Y.; Niihori T.; Kawame H.; Kurosawa K.; Ohashi H.; Tanaka Y.; Filocamo M.; Kato K.; Suzuki Y.; Kure S.; Matsubara Y.;
Nat. Genet. 37:1038-1040(2005)
Cited for: VARIANTS CSTLO ALA-12; SER-12; VAL-12 AND ASP-13; 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.