Variant position:  61

Type of variant:  Disease [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

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

Physico-chemical properties:  Change from medium size and polar (Q) to large size and basic (R)

BLOSUM score:  1

Involvement in disease:  Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:12727991}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

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.

Involvement in disease:  Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900]: Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. {ECO:0000269|PubMed:22499344}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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.

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.

Other resources:  

• Variant rs11554290 [ dbSNP | Ensembl ]

Variant position:  61

Protein sequence length:  189

Location on the sequence:   RKQVVIDGETCLLDILDTAG  Q EEYSAMRDQYMRTGEGFLCV

Residue conservation: 

Human                         RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Mouse                         RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Rat                           RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Pig                           RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Chicken                       RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Xenopus laevis                RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Zebrafish                     RKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCV

Sequence annotation in neighborhood:  

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;