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UniProtKB/Swiss-Prot O60220: Variant p.Cys66Trp

Mitochondrial import inner membrane translocase subunit Tim8 A
Gene: TIMM8A
Variant information

Variant position:  66
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Cysteine (C) to Tryptophan (W) at position 66 (C66W, p.Cys66Trp).
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 (C) to large size and aromatic (W)
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

Variant description:  In MTS; disrupts the assembly of the heterohexamer with TIMM13.
Any additional useful information about the variant.

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



Sequence information

Variant position:  66
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  97
The length of the canonical sequence.

Location on the sequence:   KCMDKPGPKLDSRAEACFVN  C VERFIDTSQFILNRLEQTQK
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                         KCMDKPGPKLDSRAEACFVNCVERFIDTSQFILNRLEQTQK

Mouse                         KCMDKPGPKLDSRAEACFVNCVERFIDTSQFILNRLEQTQK

Rat                           KCMDKPGPKLDSRAEACFVNCVERFIDTSQFILNRLEQTQK

Bovine                        KCMDKPGPKLDSRAEACFVNCVERFIDTSQFILNRLEQTQK

Xenopus laevis                KCIDRPGNKLDSRTESCLVSCVDRFIDTTLSITNRFAQIVQ

Zebrafish                     KCMDKPGPKLDSRTEVCFVNCVERFIDTSQFILNRLEQTQR

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 – 97 Mitochondrial import inner membrane translocase subunit Tim8 A
Motif 43 – 66 Twin CX3C motif
Modified residue 57 – 57 Phosphoserine
Disulfide bond 43 – 66


Literature citations

A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome.
Tranebjaerg L.; Hamel B.C.J.; Gabreels F.J.M.; Renier W.O.; Van Ghelue M.;
Eur. J. Hum. Genet. 8:464-467(2000)
Cited for: VARIANT MTS TRP-66;

Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex.
Roesch K.; Curran S.P.; Tranebjaerg L.; Koehler C.M.;
Hum. Mol. Genet. 11:477-486(2002)
Cited for: VARIANT MTS TRP-66;

The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1.TIM13 complexes in the mitochondrial intermembrane space.
Hofmann S.; Rothbauer U.; Muehlenbein N.; Neupert W.; Gerbitz K.-D.; Brunner M.; Bauer M.F.;
J. Biol. Chem. 277:23287-23293(2002)
Cited for: VARIANT MTS TRP-66;

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.