Home  |  Contact

UniProtKB/Swiss-Prot P11362: Variant p.Asn546Lys

Fibroblast growth factor receptor 1
Gene: FGFR1
Variant information

Variant position:  546
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 Asparagine (N) to Lysine (K) at position 546 (N546K, p.Asn546Lys).
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 (N) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Encephalocraniocutaneous lipomatosis (ECCL) [MIM:613001]: A sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present. {ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:26942290}. 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 ECCL; somatic mutation; activating mutation; strongly increased speed of the first autophosphorylation and loss of the normal sequential order of autophosphorylation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  546
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  822
The length of the canonical sequence.

Location on the sequence:   SDLISEMEMMKMIGKHKNII  N LLGACTQDGPLYVIVEYASK
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.

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 22 – 822 Fibroblast growth factor receptor 1
Topological domain 398 – 822 Cytoplasmic
Domain 478 – 767 Protein kinase
Alternative sequence 62 – 822 Missing. In isoform 3.
Alternative sequence 151 – 822 Missing. In isoform 16.
Alternative sequence 392 – 822 Missing. In isoform 17 and isoform 18.


Literature citations

The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations.
Lew E.D.; Furdui C.M.; Anderson K.S.; Schlessinger J.;
Sci. Signal. 2:RA6-RA6(2009)
Cited for: FUNCTION AS PROTO-ONCOGENE; ACTIVE SITE; MUTAGENESIS OF ASP-623; CATALYTIC ACTIVITY; PHOSPHORYLATION AT TYR-463; TYR-653; TYR-654; TYR-583; TYR-585 AND TYR-730; CHARACTERIZATION OF VARIANT ECCL LYS-546; IDENTIFICATION BY MASS SPECTROMETRY; ACTIVITY REGULATION;

Mosaic activating mutations in FGFR1 cause encephalocraniocutaneous lipomatosis.
Bennett J.T.; Tan T.Y.; Alcantara D.; Tetrault M.; Timms A.E.; Jensen D.; Collins S.; Nowaczyk M.J.; Lindhurst M.J.; Christensen K.M.; Braddock S.R.; Brandling-Bennett H.; Hennekam R.C.; Chung B.; Lehman A.; Su J.; Ng S.; Amor D.J.; Majewski J.; Biesecker L.G.; Boycott K.M.; Dobyns W.B.; O'Driscoll M.; Moog U.; McDonell L.M.;
Am. J. Hum. Genet. 98:579-587(2016)
Cited for: INVOLVEMENT IN ECCL; VARIANTS ECCL LYS-546 AND GLU-656; VARIANT MET-561;

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.