UniProtKB/SwissProt variant VAR

Variant information

Variant position:

338

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 Glycine (G) to Glutamate (E) at position 338 (G338E, p.Gly338Glu).

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 glycine (G) to medium size and acidic (E)

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 COXPD6; with early-onset severe motor neuron involvement; decreased protein levels; decreased oxidoreductase activity on cytochrome C; slowered reduction with NADH; strongly decreased NADH oxidase activity; strongly decreased NADH oxidase activity; no effect on DNA-binding.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1603223152 [ dbSNP | Ensembl ]

Sequence information

Variant position:

338

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

Protein sequence length:

613

The length of the canonical sequence.

Location on the sequence:

ALGRKARALGTEVIQLFPEK G NMGKILPEYLSNWTMEKVRR

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                         ALGRKARAL-GTEVIQLFPEKGNMGKILPEYLSNWTMEKVRR

Mouse                         ALGRKSQAS-GIEVIQLFPEKGNMGKILPQYLSNWTMEKVK

Rat                           ALGRKSQAS-GIEVIQLFPEKGNMGKILPEYLSNWTMEKVK

Drosophila                    SLAHYSRENNGGKVYQVFQENANMSKVLPNYLSRWTTAKME

Slime mold                    AINSNFQDK-NIKIDQIFPESGVLSTLFPDYLSKYATEEII

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	102 – 613	Apoptosis-inducing factor 1, mitochondrial
Region	134 – 483	FAD-dependent oxidoreductase
Binding site	336 – 336	NAD 1
Binding site	342 – 342	NAD 1
Alternative sequence	1 – 352	Missing. In isoform 5.
Alternative sequence	44 – 613	Missing. In isoform 6.
Alternative sequence	325 – 613	Missing. In isoform 4.
Beta strand	335 – 338

Literature citations

Structure/Function Relations in AIFM1 Variants Associated with Neurodegenerative Disorders.
Sevrioukova I.F.;
J. Mol. Biol. 428:3650-3665(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 103-613 IN COMPLEX WITH FAD; CHARACTERIZATION OF VARIANT SER-262; CHARACTERIZATION OF VARIANTS COXPD6 LEU-243; GLU-308 AND GLU-338; FUNCTION; DNA-BINDING; FAD-BINDING; CATALYTIC ACTIVITY; COFACTOR;

A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease.
Diodato D.; Tasca G.; Verrigni D.; D'Amico A.; Rizza T.; Tozzi G.; Martinelli D.; Verardo M.; Invernizzi F.; Nasca A.; Bellacchio E.; Ghezzi D.; Piemonte F.; Dionisi-Vici C.; Carrozzo R.; Bertini E.;
Eur. J. Hum. Genet. 24:463-466(2016)
Cited for: VARIANT COXPD6 GLU-338; CHARACTERIZATION OF VARIANT COXPD6 GLU-338;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95831: Variant p.Gly338Glu