UniProtKB/Swiss-Prot Q9Y4W6: Variant p.Ala572Thr

Mitochondrial inner membrane m-AAA protease component AFG3L2
Gene: AFG3L2
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Variant information Variant position:

572 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 Alanine (A) to Threonine (T) at position 572 (A572T, p.Ala572Thr). 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 small size and hydrophobic (A) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

Found in patients from a consanguineous family with progressive microcephaly, early onset seizures, spasticity and basal ganglia involvement; uncertain significance; decreased ATPase and ability to degrade substrate proteins. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs562861748 [ dbSNP | Ensembl ]

Sequence information Variant position:

572 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

797 The length of the canonical sequence.
Location on the sequence:

VIGGLEKKTQVLQPEEKKTV A YHEAGHAVAGWYLEHADPLL 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                         VIGGLEKKTQVLQPEEKKTVAYHEAGHAVAGWYLEHADPLL

Mouse                         VIGGLEKKTQVLQPEEKKTVAYHEAGHAVAGWYLEHADPLL

Bovine                        VIGGLEKKTQVLQPEEKKTVAYHEAGHAVAGWYLEHADPLL

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	67 – 797	Mitochondrial inner membrane m-AAA protease component AFG3L2
Topological domain	272 – 797	Mitochondrial matrix
Active site	575 – 575
Binding site	574 – 574
Binding site	578 – 578
Mutagenesis	575 – 575	E -> Q. Abolished protease activity. Loss of autocatalytic processing. Impaired proteolytic maturation of SPG7.
Helix	565 – 584

Literature citations
Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease.
Puchades C.; Ding B.; Song A.; Wiseman R.L.; Lander G.C.; Glynn S.E.;
Mol. Cell 75:1073-1085(2019)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS) OF 272-797 IN COMPLEX WITH ZINC; ADP AND PEPTIDE SUBSTRATE; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; SUBUNIT; SUBCELLULAR LOCATION; MUTAGENESIS OF PHE-289; LEU-299; MET-380; PHE-421; GLU-575 AND TRP-779; CHARACTERIZATION OF VARIANTS SCA28 THR-432; CYS-616; ARG-666 AND THR-688; CHARACTERIZATION OF VARIANT THR-572; Recessive AFG3L2 Mutation Causes Progressive Microcephaly, Early Onset Seizures, Spasticity, and Basal Ganglia Involvement.
Eskandrani A.; AlHashem A.; Ali E.S.; AlShahwan S.; Tlili K.; Hundallah K.; Tabarki B.;
Pediatr. Neurol. 71:24-28(2017)
Cited for: VARIANT THR-572;

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.