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UniProtKB/Swiss-Prot P13716: Variant p.Lys59Asn

Delta-aminolevulinic acid dehydratase
Gene: ALAD
Variant information

Variant position:  59
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 Lysine (K) to Asparagine (N) at position 59 (K59N, p.Lys59Asn).
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 basic (K) to medium size and polar (N)
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:  Allele ALAD*2; ALAD*2 heterozygous or homozygous carriers have significantly higher blood lead levels than ALAD*1 homozygotes when exposed to environmental lead; fully active octamer.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  59
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:   DVPDDIQPITSLPGVARYGV  K RLEEMLRPLVEEGLRCVLIF
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.

TypePositionsDescription
Chain 1 – 330 Delta-aminolevulinic acid dehydratase
Helix 58 – 71


Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT ASN-59;

The delta-aminolevulinate dehydratase polymorphism: higher blood lead levels in lead workers and environmentally exposed children with the 1-2 and 2-2 isozymes.
Wetmur J.G.; Lehnert G.; Desnick R.J.;
Environ. Res. 56:109-119(1991)
Cited for: POLYMORPHISM; VARIANT ASN-59;

The molecular mechanism of lead inhibition of human porphobilinogen synthase.
Jaffe E.K.; Martins J.; Li J.; Kervinen J.; Dunbrack R.L. Jr.;
J. Biol. Chem. 276:1531-1537(2001)
Cited for: ACTIVITY REGULATION; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; COFACTOR; IDENTIFICATION BY MASS SPECTROMETRY; MUTAGENESIS OF CYS-122; CYS-124; HIS-131; CYS-132 AND CYS-223; CHARACTERIZATION OF VARIANT ASN-59;

Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning.
Wetmur J.G.; Kaya A.H.; Plewinska M.; Desnick R.J.;
Am. J. Hum. Genet. 49:757-763(1991)
Cited for: POLYMORPHISM; VARIANT ASN-59;

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;

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.