UniProtKB/Swiss-Prot P01116: Variant p.Val14Ile

GTPase KRas
Gene: KRAS
Chromosomal location: 12p12.1
Variant information

Variant position:  14
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Valine (V) to Isoleucine (I) at position 14 (V14I, p.Val14Ile).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Variant description:  In NS3; affects activity and impairs responsiveness to GTPase activating proteins; characterized by a strong increase of both intrinsic and guanine nucleotide exchanged factor-catalyzed nucleotide exchange leading to an increased level of the activated state.
Any additional useful information about the variant.



Sequence information

Variant position:  14
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:   MTEYKLVVVGAGG  V GKSALTIQLIQNHFVDEYDP
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                         MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDP

Mouse                         MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDP

Rat                           MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDP

Xenopus laevis                MTEYKLVVVGAVGVGKSALTIQLIQNHFVDEYDP

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 KRas
Initiator methionine 1 – 1 Removed; alternate
Chain 2 – 186 GTPase KRas, N-terminally processed
Nucleotide binding 10 – 17 GTP
Modified residue 1 – 1 N-acetylmethionine; in GTPase KRas; alternate
Modified residue 2 – 2 N-acetylthreonine; in GTPase KRas, N-terminally processed


Literature citations

Germline KRAS mutations cause Noonan syndrome.
Schubbert S.; Zenker M.; Rowe S.L.; Boell S.; Klein C.; Bollag G.; van der Burgt I.; Musante L.; Kalscheuer V.; Wehner L.-E.; Nguyen H.; West B.; Zhang K.Y.J.; Sistermans E.; Rauch A.; Niemeyer C.M.; Shannon K.; Kratz C.P.;
Nat. Genet. 38:331-336(2006)
Cited for: VARIANTS NS3 ILE-14 AND ILE-58; VARIANT CFC2 ARG-34; CHARACTERIZATION OF VARIANTS NS3 ILE-14 AND ILE-58;

Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations.
Zenker M.; Lehmann K.; Schulz A.L.; Barth H.; Hansmann D.; Koenig R.; Korinthenberg R.; Kreiss-Nachtsheim M.; Meinecke P.; Morlot S.; Mundlos S.; Quante A.S.; Raskin S.; Schnabel D.; Wehner L.E.; Kratz C.P.; Horn D.; Kutsche K.;
J. Med. Genet. 44:131-135(2007)
Cited for: VARIANTS NS3 ILE-14; ARG-22; LEU-34; GLN-34; MET-36 AND VAL-153 (ISOFORM 2); VARIANT CFC2 GLU-22; VARIANT NS3/CFC2 ILE-156 (ISOFORM 2); VARIANTS ASN-5 AND LEU-156 (ISOFORM 2);

Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders.
Gremer L.; Merbitz-Zahradnik T.; Dvorsky R.; Cirstea I.C.; Kratz C.P.; Zenker M.; Wittinghofer A.; Ahmadian M.R.;
Hum. Mutat. 32:33-43(2011)
Cited for: CHARACTERIZATION OF VARIANTS NS3 ILE-14; ARG-22; LEU-34; ILE-58 AND VAL-153 (ISOFORM 2); CHARACTERIZATION OF VARIANTS CFC2 GLU-22; ARG-34 AND ARG-60; CHARACTERIZATION OF VARIANTS ASN-5 AND LEU-156 (ISOFORM 2);

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.