UniProtKB/SwissProt variant VAR

Variant information

Variant position:

61

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 61 (Q61K, p.Gln61Lys).

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:

Melanocytic nevus syndrome, congenital (CMNS) [MIM:137550]: A syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip. {ECO:0000269|PubMed:18633438, ECO:0000269|PubMed:23392294}. 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.

Involvement in disease:

Melanosis, neurocutaneous (NCMS) [MIM:249400]: A rare congenital disease characterized by the presence of giant or multiple melanocytic nevi on the skin, foci of melanin-producing cells within the brain parenchyma, and infiltration of leptomeninges by abnormal melanin deposits. Neurologic abnormalities include seizures, hydrocephalus, arachnoid cysts, tumors, and syringomyelia. Some patients may develop malignant melanoma. {ECO:0000269|PubMed:23392294}. 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 CMNS and NCMS; somatic mutation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913254 [ dbSNP | Ensembl ]

Sequence information

Variant position:

61

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:

RKQVVIDGETCLLDILDTAG Q EEYSAMRDQYMRTGEGFLCV

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                         RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Mouse                         RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Rat                           RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Pig                           RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Chicken                       RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Xenopus laevis                RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Zebrafish                     RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

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.

Type	Positions	Description
Chain	1 – 186	GTPase NRas
Nucleotide binding	57 – 61	GTP

Literature citations

Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.
Kinsler V.A.; Thomas A.C.; Ishida M.; Bulstrode N.W.; Loughlin S.; Hing S.; Chalker J.; McKenzie K.; Abu-Amero S.; Slater O.; Chanudet E.; Palmer R.; Morrogh D.; Stanier P.; Healy E.; Sebire N.J.; Moore G.E.;
J. Invest. Dermatol. 133:2229-2236(2013)
Cited for: VARIANTS CMNS ARG-61 AND LYS-61; VARIANTS NCMS ARG-61 AND LYS-61;

UniProtKB/Swiss-Prot P01111: Variant p.Gln61Lys