UniProtKB/Swiss-Prot P13716: Variant p.Phe12Leu

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 12 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Phenylalanine (F) to Leucine (L) at position 12 (F12L, p.Phe12Leu). 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 aromatic (F) to medium size and hydrophobic (L) 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
Polymorphism: Genetic variation in ALAD influences susceptibility to lead poisoning in individuals exposed to high amount of environmental lead. There are two common alleles: allele ALAD*1 and allele ALAD*2 resulting in 3 isozymes: ALAD 1-1, ALAD 1-2, and ALAD 2-2. Individuals with ALAD 1-2 or ALAD 2-2 isozymes have levels of blood lead higher than those in individuals with ALAD 1-1 isozyme. The sequence shown corresponds to allele ALAD*1. Additional information on the polymorphism described.
Variant description: In an asymptomatic patient with ALAD deficiency; also found in a hereditary coproporphyria patient carrying the R-279 mutation in CPOX; hexamer with almost no residual activity. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs121912984 [ dbSNP | Ensembl ]

Sequence information

Variant position: 12 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 330 The length of the canonical sequence.
Location on the sequence: MQPQSVLHSGY F HPLLRAWQTATTTLNASNLI 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	1 – 330	Delta-aminolevulinic acid dehydratase
Alternative sequence	1 – 38	MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVT -> MPPTSSTPSLSRPGLGQAGKPDTGSHPPPTISTSIFLSCFPTIPLSRPRTTGPSHSYQSISHPRSCR. In isoform 2.
Beta strand	11 – 13

Literature citations

Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.
Breinig S.; Kervinen J.; Stith L.; Wasson A.S.; Fairman R.; Wlodawer A.; Zdanov A.; Jaffe E.K.;
Nat. Struct. Biol. 10:757-763(2003)
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT LEU-12 IN COMPLEX WITH SUBSTRATE ANALOG; SUBUNIT; IDENTIFICATION BY MASS SPECTROMETRY; CATALYTIC ACTIVITY; ACTIVITY REGULATION; A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity.
Akagi R.; Yasui Y.; Harper P.; Sassa S.;
Br. J. Haematol. 106:931-937(1999)
Cited for: VARIANT LEU-12; CHARACTERIZATION OF VARIANT LEU-12; Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient.
Akagi R.; Inoue R.; Muranaka S.; Tahara T.; Taketani S.; Anderson K.E.; Phillips J.D.; Sassa S.;
Br. J. Haematol. 132:237-243(2006)
Cited for: VARIANT LEU-12; ALAD porphyria is a conformational disease.
Jaffe E.K.; Stith L.;
Am. J. Hum. Genet. 80:329-337(2007)
Cited for: CHARACTERIZATION OF VARIANTS AHEPP ARG-133; MET-153; TRP-240; THR-274 AND MET-275; CHARACTERIZATION OF VARIANTS LEU-12 AND ASN-59;