UniProtKB/SwissProt variant VAR

Variant information

Variant position:

8

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 Tyrosine (Y) to Cysteine (C) at position 8 (Y8C, p.Tyr8Cys).

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 aromatic (Y) to medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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.

Any additional useful information about the variant.

Sequence information

Variant position:

8

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

Protein sequence length:

213

The length of the canonical sequence.

Location on the sequence:

MVQSCSA Y GCKNRYDKDKPVSFHKFPLT

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                         MVQSCSAYGCKNRYDKDKPVSFHKFPLT

Mouse                         MVQSCSAYGCKNRYDKDKPVSFHKFPLT

Rat                           MVQSCSAYGCKNRYDKDKPVSFHKFPLT

Bovine                        MVQSCSAYGCKNRYDKDKPVSFHKFPLT

Xenopus tropicalis            MVQSCSAYGCKNRYDKDKPISFHKFPLK

Zebrafish                     MVQSCSAYGCKNRYQKDRNISFHKFPLA

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.

Type	Positions	Description
Chain	1 – 213	THAP domain-containing protein 1
Zinc finger	1 – 81	THAP-type
Mutagenesis	4 – 4	S -> A. Does not affect DNA-binding.
Mutagenesis	5 – 5	C -> A. Abolishes DNA- and zinc-binding.
Mutagenesis	6 – 6	S -> A. Does not affect DNA-binding.
Mutagenesis	8 – 8	Y -> A. Does not affect DNA-binding.
Mutagenesis	10 – 10	C -> A. Abolishes DNA- and zinc-binding.
Mutagenesis	11 – 11	K -> A. Partially affects DNA-binding.
Mutagenesis	16 – 16	K -> A. Does not affect DNA-binding.
Mutagenesis	24 – 24	K -> A. Strongly affects DNA-binding.
Mutagenesis	26 – 26	P -> A. Abolishes DNA- and zinc-binding.
Mutagenesis	27 – 27	L -> A. Partially affects DNA-binding.
Mutagenesis	28 – 28	T -> A. Does not affect DNA-binding.
Beta strand	6 – 9

Literature citations

THAP1 mutations (DYT6) are an additional cause of early-onset dystonia.
Houlden H.; Schneider S.A.; Paudel R.; Melchers A.; Schwingenschuh P.; Edwards M.; Hardy J.; Bhatia K.P.;
Neurology 74:846-850(2010)
Cited for: VARIANTS DYT6 PHE-6; CYS-8; ARG-26; SER-136 AND GLN-169;

UniProtKB/Swiss-Prot Q9NVV9: Variant p.Tyr8Cys