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UniProtKB/Swiss-Prot P00533: Variant p.Gly428Asp

Epidermal growth factor receptor
Gene: EGFR
Variant information

Variant position:  428
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 Glycine (G) to Aspartate (D) at position 428 (G428D, p.Gly428Asp).
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 glycine (G) to medium size and acidic (D)
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:  Inflammatory skin and bowel disease, neonatal, 2 (NISBD2) [MIM:616069]: A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized. {ECO:0000269|PubMed:24691054}. 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 NISBD2; loss of function; the mutant does not localize to the cell membrane; has diffuse cytoplasmic localization.
Any additional useful information about the variant.

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



Sequence information

Variant position:  428
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1210
The length of the canonical sequence.

Location on the sequence:   QAWPENRTDLHAFENLEIIR  G RTKQHGQFSLAVVSLNITSL
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                         QAWPENRTDLHAFENLEIIRGRTKQHGQF-SLAVVSLNITSL

Rhesus macaque                QAWPENRTDLHAFENLEIIRGRTKQHGQF-SLAVVSLNITS

Mouse                         QAWPDNWTDLHAFENLEIIRGRTKQHGQF-SLAVVGLNITS

Drosophila                    EGTHPQFRNLSYFRNLETIHGRQLMESMFAALAIVKSSLYS

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 25 – 1210 Epidermal growth factor receptor
Topological domain 25 – 645 Extracellular
Repeat 390 – 600 Approximate
Glycosylation 413 – 413 N-linked (GlcNAc...) asparagine
Glycosylation 444 – 444 N-linked (GlcNAc...) asparagine
Alternative sequence 406 – 1210 Missing. In isoform 2.
Mutagenesis 429 – 429 R -> E. Abolishes autophosphorylation and activation of downstream kinases.


Literature citations

Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR.
Campbell P.; Morton P.E.; Takeichi T.; Salam A.; Roberts N.; Proudfoot L.E.; Mellerio J.E.; Aminu K.; Wellington C.; Patil S.N.; Akiyama M.; Liu L.; McMillan J.R.; Aristodemou S.; Ishida-Yamamoto A.; Abdul-Wahab A.; Petrof G.; Fong K.; Harnchoowong S.; Stone K.L.; Harper J.I.; McLean W.H.; Simpson M.A.; Parsons M.; McGrath J.A.;
J. Invest. Dermatol. 134:2570-2578(2014)
Cited for: VARIANT NISBD2 ASP-428; CHARACTERIZATION OF VARIANT NISBD2 ASP-428; INVOLVEMENT IN NISBD2;

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.