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UniProtKB/Swiss-Prot P21860: Variant p.Ala1337Thr

Receptor tyrosine-protein kinase erbB-3
Gene: ERBB3
Variant information

Variant position:  1337
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 Alanine (A) to Threonine (T) at position 1337 (A1337T, p.Ala1337Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
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:  Erythroleukemia, familial (FERLK) [MIM:133180]: An autosomal dominant myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood. Disease penetrance is incomplete. {ECO:0000269|PubMed:27416908}. Note=Disease susceptibility may be 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 FERLK; risk factor for erythroleukemia; results in increased ERBB-mediated signaling; results in a block of erythroid differentiation and increased cell proliferation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1337
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1342
The length of the canonical sequence.

Location on the sequence:   EATDSAFDNPDYWHSRLFPK  A NAQRT
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                         EATDSAFDNPDYWHSRLFPKANAQRT

Mouse                         EATDSAFDNPDYWHSRLFPKANAQRI

Rat                           EATDSAFDNPDYWHSRLFPKANAQRT

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 20 – 1342 Receptor tyrosine-protein kinase erbB-3
Topological domain 665 – 1342 Cytoplasmic
Alternative sequence 184 – 1342 Missing. In isoform 2.
Alternative sequence 332 – 1342 Missing. In isoform 3.


Literature citations

A germline ERBB3 variant is a candidate for predisposition to erythroid MDS/erythroleukemia.
Braunstein E.M.; Li R.; Sobreira N.; Marosy B.; Hetrick K.; Doheny K.; Gocke C.D.; Valle D.; Brodsky R.A.; Cheng L.;
Leukemia 30:2242-2245(2016)
Cited for: VARIANT FERLK THR-1337; CHARACTERIZATION OF VARIANT FERLK THR-1337; INVOLVEMENT IN FERLK; FUNCTION;

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.