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UniProtKB/Swiss-Prot Q9NVV9: Variant p.Ile149Thr

THAP domain-containing protein 1
Gene: THAP1
Variant information

Variant position:  149
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 Isoleucine (I) to Threonine (T) at position 149 (I149T, p.Ile149Thr).
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 (I) to medium size and polar (T)
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:  Dystonia 6, torsion (DYT6) [MIM:602629]: A primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterized by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions. {ECO:0000269|PubMed:19182804, ECO:0000269|PubMed:19345147, ECO:0000269|PubMed:19908320, ECO:0000269|PubMed:19908325, ECO:0000269|PubMed:20083799, ECO:0000269|PubMed:20211909, ECO:0000269|PubMed:20629133, ECO:0000269|PubMed:20669277, ECO:0000269|PubMed:20687191, ECO:0000269|PubMed:20825472, ECO:0000269|PubMed:21110056, ECO:0000269|PubMed:21425335, ECO:0000269|PubMed:21425341, ECO:0000269|PubMed:21800139, ECO:0000269|PubMed:21839475, ECO:0000269|PubMed:21847143, ECO:0000269|PubMed:22377579, ECO:0000269|PubMed:25385508, ECO:0000269|PubMed:28299530, ECO:0000269|Ref.3}. 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 DYT6; no effect on dimerization.
Any additional useful information about the variant.

Sequence information

Variant position:  149
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  213
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 – 213 THAP domain-containing protein 1
Region 139 – 185 Involved in homodimer formation
Coiled coil 139 – 190
Alternative sequence 54 – 213 Missing. In isoform 2.

Literature citations

Adult-onset leg dystonia due to a missense mutation in THAP1.
Van Gerpen J.A.; Ledoux M.S.; Wszolek Z.K.;
Mov. Disord. 25:1306-1307(2010)
Cited for: VARIANT DYT6 THR-149;

Novel THAP1 sequence variants in primary dystonia.
Xiao J.; Zhao Y.; Bastian R.W.; Perlmutter J.S.; Racette B.A.; Tabbal S.D.; Karimi M.; Paniello R.C.; Wszolek Z.K.; Uitti R.J.; Van Gerpen J.A.; Simon D.K.; Tarsy D.; Hedera P.; Truong D.D.; Frei K.P.; Dev Batish S.; Blitzer A.; Pfeiffer R.F.; Gong S.; LeDoux M.S.;
Neurology 74:229-238(2010)
Cited for: VARIANTS DYT6 CYS-9; GLY-17; SER-132; THR-149; THR-166 AND LYS-187;

In-depth Characterization of the Homodimerization Domain of the Transcription Factor THAP1 and Dystonia-Causing Mutations Therein.
Richter A.; Hollstein R.; Hebert E.; Vulinovic F.; Eckhold J.; Osmanovic A.; Depping R.; Kaiser F.J.; Lohmann K.;
J. Mol. Neurosci. 62:11-16(2017)
Cited for: SUBUNIT; REGION; VARIANTS DYT6 VAL-143; THR-149; PRO-150; THR-166; GLN-169; ARG-170; GLY-174; PRO-177 AND SER-180; CHARACTERIZATION OF VARIANTS DYT6 THR-149; PRO-150; THR-166; GLN-169; ARG-170; GLY-174; PRO-177 AND SER-180;

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.