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:

LP/P [Disclaimer]

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:

From Glutamine (Q) to Arginine (R) at position 61 (Q61R, p.Gln61Arg).

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 (R)

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

Variant description:

In CMNS, NCMS, KNEN and NMTC2; also found in lung carcinoma cell and melanoma; impaired GTP hydrolysis activity, trapping NRAS in a constitutive GTP-bound active conformation; promotes melanomagenesis.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs11554290 [ 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

Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay.
Raybaud F.; Noguchi T.; Marics I.; Adelaide J.; Planche J.; Batoz M.; Aubet C.; de Lapeyriere O.; Birnbaum D.;
Cancer Res. 48:950-953(1988)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-96; VARIANT ARG-61;

RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.
Nikiforova M.N.; Lynch R.A.; Biddinger P.W.; Alexander E.K.; Dorn G.W. II; Tallini G.; Kroll T.G.; Nikiforov Y.E.;
J. Clin. Endocrinol. Metab. 88:2318-2326(2003)
Cited for: INVOLVEMENT IN NMTC2; VARIANT NMTC2 ARG-61;

Pharmacological targeting of STK19 inhibits oncogenic NRAS-driven melanomagenesis.
Yin C.; Zhu B.; Zhang T.; Liu T.; Chen S.; Liu Y.; Li X.; Miao X.; Li S.; Mi X.; Zhang J.; Li L.; Wei G.; Xu Z.X.; Gao X.; Huang C.; Wei Z.; Goding C.R.; Wang P.; Deng X.; Cui R.;
Cell 176:1113-1127(2019)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-89; MUTAGENESIS OF SER-89; VARIANT ARG-61; CHARACTERIZATION OF VARIANT ARG-61;

Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis.
Dessars B.; De Raeve L.E.; Morandini R.; Lefort A.; El Housni H.; Ghanem G.E.; Van den Eynde B.J.; Ma W.; Roseeuw D.; Vassart G.; Libert F.; Heimann P.;
J. Invest. Dermatol. 129:139-147(2009)
Cited for: VARIANTS CMNS ARG-13 AND ARG-61;

Keratinocytic epidermal nevi are associated with mosaic RAS mutations.
Hafner C.; Toll A.; Gantner S.; Mauerer A.; Lurkin I.; Acquadro F.; Fernandez-Casado A.; Zwarthoff E.C.; Dietmaier W.; Baselga E.; Parera E.; Vicente A.; Casanova A.; Cigudosa J.; Mentzel T.; Pujol R.M.; Landthaler M.; Real F.X.;
J. Med. Genet. 49:249-253(2012)
Cited for: VARIANTS KNEN ASP-12; LEU-34 AND ARG-61;

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 variant pages

UniProtKB/Swiss-Prot P01111: Variant p.Gln61Arg