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UniProtKB/Swiss-Prot Q9UM73: Variant p.Arg1275Gln

ALK tyrosine kinase receptor
Gene: ALK
Variant information

Variant position:  1275
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 Arginine (R) to Glutamine (Q) at position 1275 (R1275Q, p.Arg1275Gln).
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 large size and basic (R) to medium size and polar (Q)
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:  Neuroblastoma 3 (NBLST3) [MIM:613014]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. {ECO:0000269|PubMed:18724359, ECO:0000269|PubMed:18923523, ECO:0000269|PubMed:18923525, ECO:0000269|PubMed:21242967}. Note=Disease susceptibility is associated with variations 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 NBLST3; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1275
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1620
The length of the canonical sequence.

Location on the sequence:   CLLTCPGPGRVAKIGDFGMA  R DIYRASYYRKGGCAMLPVKW
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                         CLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKW

Mouse                         CLLTCPGAGRIAKIGDFGMARDIYRASYYRKGGCAMLPVKW

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 19 – 1620 ALK tyrosine kinase receptor
Topological domain 1060 – 1620 Cytoplasmic
Domain 1116 – 1392 Protein kinase
Binding site 1270 – 1270 ATP
Modified residue 1278 – 1278 Phosphotyrosine
Helix 1272 – 1280


Literature citations

Identification of ALK as a major familial neuroblastoma predisposition gene.
Mosse Y.P.; Laudenslager M.; Longo L.; Cole K.A.; Wood A.; Attiyeh E.F.; Laquaglia M.J.; Sennett R.; Lynch J.E.; Perri P.; Laureys G.; Speleman F.; Kim C.; Hou C.; Hakonarson H.; Torkamani A.; Schork N.J.; Brodeur G.M.; Tonini G.P.; Rappaport E.; Devoto M.; Maris J.M.;
Nature 455:930-935(2008)
Cited for: VARIANTS NBLST3 ASN-1091; ALA-1128; ARG-1166; ASN-1171; ILE-1174; PRO-1192; CYS-1245; VAL-1245 THR-1250 AND GLN-1275;

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.
Janoueix-Lerosey I.; Lequin D.; Brugieres L.; Ribeiro A.; de Pontual L.; Combaret V.; Raynal V.; Puisieux A.; Schleiermacher G.; Pierron G.; Valteau-Couanet D.; Frebourg T.; Michon J.; Lyonnet S.; Amiel J.; Delattre O.;
Nature 455:967-970(2008)
Cited for: VARIANTS NBLST3 VAL-1174; LEU-1174; CYS-1174; PRO-1192; GLN-1275 AND SER-1278; VARIANT LEU-1275;

Activating mutations in ALK provide a therapeutic target in neuroblastoma.
George R.E.; Sanda T.; Hanna M.; Froehling S.; Luther W. II; Zhang J.; Ahn Y.; Zhou W.; London W.B.; McGrady P.; Xue L.; Zozulya S.; Gregor V.E.; Webb T.R.; Gray N.S.; Gilliland D.G.; Diller L.; Greulich H.; Morris S.W.; Meyerson M.; Look A.T.;
Nature 455:975-978(2008)
Cited for: VARIANTS NBLST3 MET-1151; LEU-1174; THR-1234; CYS-1245 AND GLN-1275;

The constitutive activity of the ALK mutated at positions F1174 or R1275 impairs receptor trafficking.
Mazot P.; Cazes A.; Boutterin M.C.; Figueiredo A.; Raynal V.; Combaret V.; Hallberg B.; Palmer R.H.; Delattre O.; Janoueix-Lerosey I.; Vigny M.;
Oncogene 30:2017-2025(2011)
Cited for: CHARACTERIZATION OF VARIANTS NBLST3 LEU-1174; VAL-1174 AND GLN-1275;

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.