UniProtKB/Swiss-Prot O95831: Variant p.Pro475Leu

Apoptosis-inducing factor 1, mitochondrial
Gene: AIFM1
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Variant information Variant position:

475 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Proline (P) to Leucine (L) at position 475 (P475L, p.Pro475Leu). 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
Variant description:

In DFNX5; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs724160022 [ dbSNP | Ensembl ]

Sequence information Variant position:

475 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:

HDHAVVSGRLAGENMTGAAK P YWHQSMFWSDLGPDVGYEAI 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                         HDHAVVSGRLAGENMTGAAK--PYWHQSMFWSDLGPDVGYEAI

Mouse                         HDHAVVSGRLAGENMTGAAK--PYWHQSMFWSDLGPDVGYE

Rat                           HDHAVVSGRLAGENMTGAAK--PYWHQSMFWSDLGPDVGYE

Drosophila                    HDHSVVSGRLAGENMTGAKK--PYQHQSMFWSDLGPEIGYE

Slime mold                    HDHARATGEMAGSNMSTKDTPAPYTYQPFFWSDLTPGVGFE

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	483 – 483
Binding site	483 – 483
Binding site	493 – 493
Alternative sequence	44 – 613	Missing. In isoform 6.
Alternative sequence	325 – 613	Missing. In isoform 4.
Mutagenesis	477 – 477	W -> A. Disrupts dimerization; when associated with A-443--445-A.
Mutagenesis	480 – 480	S -> A. Allows dimerization in absence of NADH.
Mutagenesis	485 – 485	D -> A. Increases protein dimerization at lower NADH levels.

Literature citations
Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder.
Zong L.; Guan J.; Ealy M.; Zhang Q.; Wang D.; Wang H.; Zhao Y.; Shen Z.; Campbell C.A.; Wang F.; Yang J.; Sun W.; Lan L.; Ding D.; Xie L.; Qi Y.; Lou X.; Huang X.; Shi Q.; Chang S.; Xiong W.; Yin Z.; Yu N.; Zhao H.; Wang J.; Wang J.; Salvi R.J.; Petit C.; Smith R.J.; Wang Q.;
J. Med. Genet. 52:523-531(2015)
Cited for: INVOLVEMENT IN DFNX5; VARIANTS DFNX5 ALA-260; PHE-344; ARG-360; GLN-422; TRP-422; CYS-430; GLN-451; VAL-472; LEU-475; MET-498 AND MET-591;

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.