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UniProtKB/Swiss-Prot Q8TF17: Variant p.Arg529Gln

SH3 domain and tetratricopeptide repeat-containing protein 2
Gene: SH3TC2
Variant information

Variant position:  529
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 Arginine (R) to Glutamine (Q) at position 529 (R529Q, p.Arg529Gln).
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 large size and basic (R) to medium size and polar (Q)
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:  Charcot-Marie-Tooth disease 4C (CMT4C) [MIM:601596]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4C is characterized by onset in childhood, early-onset scoliosis and a distinct Schwann cell pathology. {ECO:0000269|PubMed:14574644}. 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 CMT4C.
Any additional useful information about the variant.

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



Sequence information

Variant position:  529
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1288
The length of the canonical sequence.

Location on the sequence:   AYLEASRKWAKKSHMTWAHA  R LCFLLGRLSIRKVKLSQARV
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                         AYLEASRKWAKKSHMTWAHARLCFLLGRLSIRKVKLSQARV

Mouse                         AYLETSRKWAKMSHMTWAHARLCFLLGRLSIRKTKLSQARV

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 – 1288 SH3 domain and tetratricopeptide repeat-containing protein 2
Repeat 528 – 561 TPR 1
Alternative sequence 1 – 1138 Missing. In isoform 2 and isoform 3.


Literature citations

Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.
Senderek J.; Bergmann C.; Stendel C.; Kirfel J.; Verpoorten N.; De Jonghe P.; Timmerman V.; Chrast R.; Verheijen M.H.G.; Lemke G.; Battaloglu E.; Parman Y.; Erdem S.; Tan E.; Topaloglu H.; Hahn A.; Mueller-Felber W.; Rizzuto N.; Fabrizi G.M.; Stuhrmann M.; Rudnik-Schoeneborn S.; Zuechner S.; Schroeder J.M.; Buchheim E.; Straub V.; Klepper J.; Huehne K.; Rautenstrauss B.; Buettner R.; Nelis E.; Zerres K.;
Am. J. Hum. Genet. 73:1106-1119(2003)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); TISSUE SPECIFICITY; VARIANTS CMT4C GLN-529; LYS-657 AND CYS-658;

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.