UniProtKB/Swiss-Prot P01116: Variant p.Pro34Arg

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

Variant position:  34
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 Proline (P) to Arginine (R) at position 34 (P34R, p.Pro34Arg).
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 hydrophobic (P) 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:  Cardiofaciocutaneous syndrome 2 (CFC2) [MIM:615278]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. CFC2 patients often do not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma observed in CFC1. 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 CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors.
Any additional useful information about the variant.



Sequence information

Variant position:  34
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:   VGKSALTIQLIQNHFVDEYD  P TIEDSYRKQVVIDGETCLLD
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                         VGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLD

Mouse                         VGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLD

Rat                           VGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLD

Xenopus laevis                VGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLD

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
Chain 2 – 186 GTPase KRas, N-terminally processed
Motif 32 – 40 Effector region


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;

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.