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UniProtKB/Swiss-Prot Q04656: Variant p.Asn1304Ser

Copper-transporting ATPase 1
Gene: ATP7A
Chromosomal location: Xq13.2-q13.3
Variant information

Variant position:  1304
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 Serine (S) at position 1304 (N1304S, p.Asn1304Ser).
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 small size and polar (S)
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:  Occipital horn syndrome (OHS) [MIM:304150]: An X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities include occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga. {ECO:0000269|PubMed:11431706, ECO:0000269|PubMed:17108763, ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:9246006}. 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 OHS; has approximately 33% residual copper transport; increased protein abundance; increased localization at the plasma membrane; does not cycle back to TGN under conditions of copper depletion; does not affect interaction with ATOX1; does not affect interaction with COMMD1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1304
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1500
The length of the canonical sequence.

Location on the sequence:   AKVKQLQEEGKRVAMVGDGI  N DSPALAMANVGIAIGTGTDV
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                         AKVKQLQEEGKRVAMVGDGINDSPALAMANVGIAIGTGTDV

Mouse                         AKVKQLQEEGKRVAMVGDGINDSPALAMANVGIAIGTGTDV

Rat                           AKVKQLQEEGKRVAMVGDGINDSPALAMASVGIAIGTGTDV

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 – 1500 Copper-transporting ATPase 1
Topological domain 1012 – 1356 Cytoplasmic
Metal binding 1301 – 1301 Magnesium
Metal binding 1305 – 1305 Magnesium
Alternative sequence 82 – 1499 Missing. In isoform 6.


Literature citations

The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression.
Vonk W.I.; de Bie P.; Wichers C.G.; van den Berghe P.V.; van der Plaats R.; Berger R.; Wijmenga C.; Klomp L.W.; van de Sluis B.;
Cell. Mol. Life Sci. 69:149-163(2012)
Cited for: INTERACTION WITH ATOX1 AND COMMD1; CHARACTERIZATION OF VARIANT OHS SER-1304; CHARACTERIZATION OF VARIANTS MNKD ARG-873; ARG-1000 AND ASP-1362;

Functional copper transport explains neurologic sparing in occipital horn syndrome.
Tang J.; Robertson S.; Lem K.E.; Godwin S.C.; Kaler S.G.;
Genet. Med. 8:711-718(2006)
Cited for: VARIANT OHS SER-1304; CHARACTERIZATION OF VARIANT OHS SER-1304;

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.