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UniProtKB/Swiss-Prot P17302: Variant p.Glu227Asp

Gap junction alpha-1 protein
Gene: GJA1
Variant information

Variant position:  227
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 Glutamate (E) to Aspartate (D) at position 227 (E227D, p.Glu227Asp).
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 acidic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
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:  Erythrokeratodermia variabilis et progressiva 3 (EKVP3) [MIM:617525]: A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. {ECO:0000269|PubMed:25398053}. 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 EKVP3; loss of localization to the plasma membrane, retention in the Golgi apparatus.
Any additional useful information about the variant.

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



Sequence information

Variant position:  227
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  382
The length of the canonical sequence.

Location on the sequence:   TIFIIFMLVVSLVSLALNII  E LFYVFFKGVKDRVKGKSDPY
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                         TIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGKSDPY

                              TIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGQSDPY

Mouse                         TIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGRSDPY

Rat                           TIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGRSDPY

Pig                           TIFIIFMLVVSLVSLALNIIELFYAFFKGVKDRVKGKSDPY

Bovine                        TIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGKSDPY

Rabbit                        TIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGKSDPY

Chicken                       TIFIVFMLVVSLVSLALNIIELFYVFFKGVKDRVKGKTDPY

Xenopus laevis                TIFIWFMLIVSIVSLALNIIELFYVTYKSIKDGIKGKKDPF

Zebrafish                     TIFIIFMLVVSLFSLLLNIIELFYVLFKRIKDRVKSRQNTQ

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 1 – 382 Gap junction alpha-1 protein
Transmembrane 209 – 231 Helical
Modified residue 247 – 247 Phosphotyrosine
Cross 237 – 237 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)


Literature citations

Dominant de novo mutations in GJA1 cause erythrokeratodermia variabilis et progressiva, without features of oculodentodigital dysplasia.
Boyden L.M.; Craiglow B.G.; Zhou J.; Hu R.; Loring E.C.; Morel K.D.; Lauren C.T.; Lifton R.P.; Bilguvar K.; Paller A.S.; Choate K.A.;
J. Invest. Dermatol. 135:1540-1547(2015)
Cited for: INVOLVEMENT IN EKVP3; VARIANTS EKVP3 VAL-44 AND ASP-227; CHARACTERIZATION OF VARIANTS EKVP3 VAL-44 AND ASP-227; SUBCELLULAR LOCATION;

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.