UniProtKB/Swiss-Prot P22557: Variant p.Pro520Leu

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 520 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 520 (P520L, p.Pro520Leu). 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 SIDBA1; likely benign; associated in cis with H-560 in a patient. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs201062903 [ dbSNP | Ensembl ]

Sequence information

Variant position: 520 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 587 The length of the canonical sequence.
Location on the sequence: YVQAINYPTVPRGEELLRLA P SPHHSPQMMEDFVEKLLLAW 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.
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	50 – 587	5-aminolevulinate synthase, erythroid-specific, mitochondrial
Binding site	508 – 508
Mutagenesis	511 – 511	R -> E. 2-fold increased enzyme activity with a lower specificity for glycine and higher for succinyl-CoA.

Literature citations

Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload.
Lee P.L.; Barton J.C.; Rao S.V.; Acton R.T.; Adler B.K.; Beutler E.;
Blood Cells Mol. Dis. 36:292-297(2006)
Cited for: VARIANTS SIDBA1 LEU-520 AND HIS-560; Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations.
Bergmann A.K.; Campagna D.R.; McLoughlin E.M.; Agarwal S.; Fleming M.D.; Bottomley S.S.; Neufeld E.J.;
Pediatr. Blood Cancer 54:273-278(2010)
Cited for: VARIANTS SIDBA1 LEU-165; CYS-170; ALA-301; CYS-411; GLY-452; GLY-517 AND LEU-520; Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations.
Ducamp S.; Kannengiesser C.; Touati M.; Garcon L.; Guerci-Bresler A.; Guichard J.F.; Vermylen C.; Dochir J.; Poirel H.A.; Fouyssac F.; Mansuy L.; Leroux G.; Tertian G.; Girot R.; Heimpel H.; Matthes T.; Talbi N.; Deybach J.C.; Beaumont C.; Puy H.; Grandchamp B.;
Hum. Mutat. 32:590-597(2011)
Cited for: VARIANTS SIDBA1 HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411; GLY-452 AND HIS-572; VARIANT LEU-520; CHARACTERIZATION OF VARIANTS SIDBA1 HIS-170; HIS-218; LYS-242; ASN-263; LEU-339; CYS-375; HIS-411; GLY-452 AND HIS-572; FUNCTION; CATALYTIC ACTIVITY;