UniProtKB/SwissProt variant VAR

Variant information

Variant position:

532

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 Tryptophan (W) at position 532 (R532W, p.Arg532Trp).

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 large size and aromatic (W)

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:

Mitochondrial complex I deficiency, nuclear type 20 (MC1DN20) [MIM:611126]: An autosomal recessive metabolic disorder associated with mitochondrial complex I deficiency, resulting in multisystemic and variable manifestations. Clinical features include infantile onset of acute metabolic acidosis, Reye-like episodes (brain edema and vomiting that may rapidly progress to seizures, coma and death), exercise intolerance, hypertrophic cardiomyopathy, liver failure, muscle weakness, and neurologic dysfunction. {ECO:0000269|PubMed:17564966, ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:20929961, ECO:0000269|PubMed:21057504, ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:23836383, ECO:0000269|PubMed:23996478, ECO:0000269|PubMed:26741492}. 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 MC1DN20.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs377022708 [ dbSNP | Ensembl ]

Sequence information

Variant position:

532

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

Protein sequence length:

621

The length of the canonical sequence.

Location on the sequence:

VETLLLRFGKTIMEEQLVLK R VANILINLYGMTAVLSRASR

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                         VETLLLRFGKTIMEEQLVLKRVANILINLYGMTAVLSRASR

Mouse                         VETLLLRFGKNIVEEQLVLKRVANILINLYGMTAVLSRASR

Rat                           VETLLLRFGKTIVEEQLVLKRVANILINLYGMTAVLSRASR

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	38 – 621	Complex I assembly factor ACAD9, mitochondrial
Modified residue	521 – 521	N6-acetyllysine; alternate
Modified residue	521 – 521	N6-succinyllysine; alternate

Literature citations

Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency.
Haack T.B.; Danhauser K.; Haberberger B.; Hoser J.; Strecker V.; Boehm D.; Uziel G.; Lamantea E.; Invernizzi F.; Poulton J.; Rolinski B.; Iuso A.; Biskup S.; Schmidt T.; Mewes H.W.; Wittig I.; Meitinger T.; Zeviani M.; Prokisch H.;
Nat. Genet. 42:1131-1134(2010)
Cited for: INVOLVEMENT IN MC1DN20; VARIANTS MC1DN20 ILE-44; TRP-193; PHE-234; GLN-266; SER-303; THR-326; CYS-417 AND TRP-532;

Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene.
Gerards M.; van den Bosch B.J.; Danhauser K.; Serre V.; van Weeghel M.; Wanders R.J.; Nicolaes G.A.; Sluiter W.; Schoonderwoerd K.; Scholte H.R.; Prokisch H.; Rotig A.; de Coo I.F.; Smeets H.J.;
Brain 134:210-219(2011)
Cited for: VARIANTS MC1DN20 LYS-127; TRP-469 AND TRP-532;

Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing.
Haack T.B.; Haberberger B.; Frisch E.M.; Wieland T.; Iuso A.; Gorza M.; Strecker V.; Graf E.; Mayr J.A.; Herberg U.; Hennermann J.B.; Klopstock T.; Kuhn K.A.; Ahting U.; Sperl W.; Wilichowski E.; Hoffmann G.F.; Tesarova M.; Hansikova H.; Zeman J.; Plecko B.; Zeviani M.; Wittig I.; Strom T.M.; Schuelke M.; Freisinger P.; Meitinger T.; Prokisch H.;
J. Med. Genet. 49:277-283(2012)
Cited for: VARIANT MC1DN20 TRP-532;

UniProtKB/Swiss-Prot Q9H845: Variant p.Arg532Trp