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UniProtKB/Swiss-Prot P12235: Variant p.Leu98Pro

ADP/ATP translocase 1
Gene: SLC25A4
Chromosomal location: 4q35
Variant information

Variant position:  98
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 Leucine (L) to Proline (P) at position 98 (L98P, p.Leu98Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2 (PEOA2) [MIM:609283]: A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. {ECO:0000269|PubMed:10926541, ECO:0000269|PubMed:11756613, ECO:0000269|PubMed:12112115, ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:15792871, ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:27693233}. 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 PEOA2; decreased function in ADP transport.
Any additional useful information about the variant.

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

Sequence information

Variant position:  98
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  298
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.

Human                         VIRYFPTQALN---------FAFKDKYKQLFLGGVDRHKQ-------FWRYFA----------------GNLA

Mouse                         VIRYFPTQALN---------FAFKDKYKQIFLGGVDRHKQ-

Rat                           VIRYFPTQALN---------FAFKDKYKQIFLGGVDRHKQ-

Bovine                        VIRYFPTQALN---------FAFKDKYKQIFLGGVDRHKQ-

Rabbit                        VIRYFPTQALN---------FAFKDKYKQIFLGGVDRHKQ-


Baker's yeast                 VLRYFPTQALN---------FAFKDKIKSLLSYDRERDG--

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 2 – 298 ADP/ATP translocase 1
Transmembrane 75 – 99 Helical; Name=2
Repeat 6 – 98 Solcar 1
Binding site 80 – 80 ADP
Binding site 92 – 92 ADP

Literature citations

Recurrent de novo dominant mutations in SLC25A4 cause severe early-onset mitochondrial disease and loss of mitochondrial DNA copy number.
Thompson K.; Majd H.; Dallabona C.; Reinson K.; King M.S.; Alston C.L.; He L.; Lodi T.; Jones S.A.; Fattal-Valevski A.; Fraenkel N.D.; Saada A.; Haham A.; Isohanni P.; Vara R.; Barbosa I.A.; Simpson M.A.; Deshpande C.; Puusepp S.; Bonnen P.E.; Rodenburg R.J.; Suomalainen A.; Ounap K.; Elpeleg O.; Ferrero I.; McFarland R.; Kunji E.R.; Taylor R.W.;
Am. J. Hum. Genet. 99:860-876(2016)

A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.
Napoli L.; Bordoni A.; Zeviani M.; Hadjigeorgiou G.M.; Sciacco M.; Tiranti V.; Terentiou A.; Moggio M.; Papadimitriou A.; Scarlato G.; Comi G.P.;
Neurology 57:2295-2298(2001)
Cited for: VARIANT PEOA2 PRO-98;

Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia.
Virgilio R.; Ronchi D.; Hadjigeorgiou G.M.; Bordoni A.; Saladino F.; Moggio M.; Adobbati L.; Kafetsouli D.; Tsironi E.; Previtali S.; Papadimitriou A.; Bresolin N.; Comi G.P.;
J. Neurol. 255:1384-1391(2008)
Cited for: VARIANTS PEOA2 PRO-98 AND PRO-114;

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.