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UniProtKB/Swiss-Prot Q04656: Variant p.Thr994Ile

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

Variant position:  994
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 Threonine (T) to Isoleucine (I) at position 994 (T994I, p.Thr994Ile).
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 (T) to medium size and hydrophobic (I)
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:  Distal spinal muscular atrophy, X-linked, 3 (DSMAX3) [MIM:300489]: A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:20170900}. 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 DSMAX3; demonstrates impaired intracellular trafficking compared to control with some of the mutant protein remaining in the Golgi apparatus after exposure to copper.
Any additional useful information about the variant.

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



Sequence information

Variant position:  994
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:   YNRSISRTETIIRFAFQASI  T VLCIACPCSLGLATPTAVMV
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                         YNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMV

Mouse                         YNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMV

Rat                           YNRSISRTETIIRFAFQASITVLCIACPCSLGLATPTAVMV

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
Transmembrane 990 – 1011 Helical
Glycosylation 975 – 975 N-linked (GlcNAc...) asparagine
Alternative sequence 42 – 1038 Missing. In isoform 3.
Alternative sequence 82 – 1499 Missing. In isoform 6.


Literature citations

Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy.
Kennerson M.L.; Nicholson G.A.; Kaler S.G.; Kowalski B.; Mercer J.F.B.; Tang J.; Llanos R.M.; Chu S.; Takata R.I.; Speck-Martins C.E.; Baets J.; Almeida-Souza L.; Fischer D.; Timmerman V.; Taylor P.E.; Scherer S.S.; Ferguson T.A.; Bird T.D.; De Jonghe P.; Feely S.M.E.; Shy M.E.; Garbern J.Y.;
Am. J. Hum. Genet. 86:343-352(2010)
Cited for: VARIANTS DSMAX3 ILE-994 AND SER-1386; CHARACTERIZATION OF VARIANTS DSMAX3 ILE-994 AND SER-1386;

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.