UniProtKB/Swiss-Prot Q04656: Variant p.Leu1006Pro

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

Variant position:  1006
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 1006 (L1006P, p.Leu1006Pro).
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:  Menkes disease (MNKD) [MIM:309400]: An X-linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes. A mild form of the disease has been described, in which cerebellar ataxia and moderate developmental delay predominate. {ECO:0000269|PubMed:10079817, ECO:0000269|PubMed:10319589, ECO:0000269|PubMed:10401004, ECO:0000269|PubMed:11241493, ECO:0000269|PubMed:11350187, ECO:0000269|PubMed:15981243, ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:22992316, ECO:0000269|PubMed:7977350, ECO:0000269|PubMed:8981948}. 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 MNKD.
Any additional useful information about the variant.

Sequence information

Variant position:  1006
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1500
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 1 – 1500 Copper-transporting ATPase 1
Transmembrane 990 – 1011 Helical
Alternative sequence 42 – 1038 Missing. In isoform 3.
Alternative sequence 82 – 1499 Missing. In isoform 6.

Literature citations

Identification of point mutations in 41 unrelated patients affected with Menkes disease.
Tuemer Z.; Lund C.; Tolshave J.; Vural B.; Toennesen T.; Horn N.;
Am. J. Hum. Genet. 60:63-71(1997)
Cited for: VARIANTS MNKD PRO-629; ARG-727; PRO-1006 AND ASP-1019;

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.