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UniProtKB/Swiss-Prot P06753: Variant p.Met9Arg

Tropomyosin alpha-3 chain
Gene: TPM3
Variant information

Variant position:  9
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 Methionine (M) to Arginine (R) at position 9 (M9R, p.Met9Arg).
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 hydrophobic (M) to large size and basic (R)
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:  Nemaline myopathy 1 (NEM1) [MIM:609284]: A form of nemaline myopathy with autosomal dominant or recessive inheritance. Nemaline myopathies are disorders characterized by muscle weakness of varying onset and severity, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Autosomal dominant NEM1 is characterized by a moderate phenotype with onset between birth and early second decade of life. Weakness is diffuse and symmetric with slow progression often with need for a wheelchair in adulthood. The autosomal recessive form has onset at birth with moderate to severe hypotonia and diffuse weakness. In the most severe cases, death can occur before 2 years. Less severe cases have delayed major motor milestones, and these patients may walk, but often need a wheelchair before 10 years. {ECO:0000269|PubMed:10587521, ECO:0000269|PubMed:17376686, ECO:0000269|PubMed:24692096, ECO:0000269|PubMed:7704029}. 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 NEM1; decrease in the sensitivity of contraction to activating calcium.
Any additional useful information about the variant.

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

Sequence information

Variant position:  9
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  285
The length of the canonical sequence.

Location on the sequence:   MMEAIKKK  M QMLKLDKENALDRAEQAEAE
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.



Rat                           TIEAVKRKIQVLQ----------QQADDA

Pig                           -MEAIKKKMQMLKLDKENALDRAEQAEAE

Bovine                        -MEAIKKKMQMLKLDKENALDRAEQAEAE

Caenorhabditis elegans        LLDVLKKKMRQAR----------EEAEAA

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.

Initiator methionine 1 – 1 Removed
Chain 2 – 285 Tropomyosin alpha-3 chain
Coiled coil 1 – 285
Modified residue 2 – 2 N-acetylmethionine
Alternative sequence 1 – 127 Missing. In isoform 7.
Alternative sequence 5 – 21 IKKKMQMLKLDKENALD -> VKRKIQVLQQQADDAEE. In isoform 4 and isoform 5.

Literature citations

A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.
Laing N.G.; Wilton S.D.; Akkari P.A.; Dorosz S.; Boundy K.; Kneebone C.; Blumbergs P.; White S.; Watkins H.; Love D.R.; Haan E.;
Nat. Genet. 9:75-79(1995)
Cited for: VARIANT NEM1 ARG-9;

A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production.
Michele D.E.; Albayya F.P.; Metzger J.M.;
J. Clin. Invest. 104:1575-1581(1999)

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.