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UniProtKB/Swiss-Prot P35916: Variant p.Leu1044Pro

Vascular endothelial growth factor receptor 3
Gene: FLT4
Variant information

Variant position:  1044
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 Leucine (L) to Proline (P) at position 1044 (L1044P, p.Leu1044Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Lymphatic malformation 1 (LMPHM1) [MIM:153100]: A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM1 is an autosomal dominant form with variable expression and severity. Onset is usually at birth or in early childhood but can occur later. Affected individuals manifest lymphedema, predominantly in the lower limbs, and hypoplasia of lymphatic vessels. Additional features are hemangioma and nail dysplasia or papillomatosis. {ECO:0000269|PubMed:10835628, ECO:0000269|PubMed:10856194, ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:16924388, ECO:0000269|PubMed:16965327, ECO:0000269|PubMed:17458866, ECO:0000269|PubMed:19289394, ECO:0000269|PubMed:26091405, ECO:0000269|PubMed:9817924}. 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 LMPHM1; loss of kinase activity.
Any additional useful information about the variant.

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

Sequence information

Variant position:  1044
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1363
The length of the canonical sequence.

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.





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.

Chain 25 – 1363 Vascular endothelial growth factor receptor 3
Topological domain 797 – 1363 Cytoplasmic
Domain 845 – 1173 Protein kinase
Active site 1037 – 1037 Proton acceptor
Modified residue 1063 – 1063 Phosphotyrosine; by autocatalysis and SRC
Alternative sequence 766 – 1298 Missing. In isoform 3.
Mutagenesis 1063 – 1063 Y -> F. Loss of phosphorylation site. No effect on stimulation of cell proliferation and cell migration.

Literature citations

Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema.
Karkkainen M.J.; Ferrell R.E.; Lawrence E.C.; Kimak M.A.; Levinson K.L.; McTigue M.A.; Alitalo K.; Finegold D.N.;
Nat. Genet. 25:153-159(2000)

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.