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UniProtKB/Swiss-Prot P08397: Variant p.Ala252Thr

Porphobilinogen deaminase
Gene: HMBS
Chromosomal location: 11q23.2-qter
Variant information

Variant position:  252
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Threonine (T) at position 252 (A252T, p.Ala252Thr).
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

Involvement in disease:  Acute intermittent porphyria (AIP) [MIM:176000]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10453740, ECO:0000269|PubMed:10494093, ECO:0000269|PubMed:10502788, ECO:0000269|PubMed:10602775, ECO:0000269|PubMed:10657149, ECO:0000269|PubMed:10782018, ECO:0000269|PubMed:11013452, ECO:0000269|PubMed:11030413, ECO:0000269|PubMed:11399210, ECO:0000269|PubMed:11857754, ECO:0000269|PubMed:12372055, ECO:0000269|PubMed:12406973, ECO:0000269|PubMed:12773194, ECO:0000269|PubMed:1301948, ECO:0000269|PubMed:1427766, ECO:0000269|PubMed:14669009, ECO:0000269|PubMed:14757946, ECO:0000269|PubMed:1496994, ECO:0000269|PubMed:14970743, ECO:0000269|PubMed:15669678, ECO:0000269|PubMed:16211556, ECO:0000269|PubMed:1714233, ECO:0000269|PubMed:18406650, ECO:0000269|PubMed:19138865, ECO:0000269|PubMed:19292878, ECO:0000269|PubMed:2243128, ECO:0000269|PubMed:23815679, ECO:0000269|PubMed:25703257, ECO:0000269|PubMed:25870942, ECO:0000269|PubMed:7757070, ECO:0000269|PubMed:7962538, ECO:0000269|PubMed:8081367, ECO:0000269|PubMed:8262523, ECO:0000269|PubMed:8268934, ECO:0000269|PubMed:8270254, ECO:0000269|PubMed:8270256, ECO:0000269|PubMed:8401516, ECO:0000269|PubMed:8825929, ECO:0000269|PubMed:9199558, ECO:0000269|PubMed:9225970, ECO:0000269|PubMed:9463797, ECO:0000269|PubMed:9654202, ECO:0000269|Ref.46}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In AIP.
Any additional useful information about the variant.

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



Sequence information

Variant position:  252
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  361
The length of the canonical sequence.

Location on the sequence:   LDLVGVLHDPETLLRCIAER  A FLRHLEGGCSVPVAVHTAMK
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                         LDLVGVLHDPETLLRCIAERAFLRHLEGGCSVPVAVHTAMK-----

Mouse                         LDLVSVLHDPETLLRCIAERAFLRHLEGGCSVPVAVHTVMK

Rat                           LDLVGVLHDPETLLRCIAERAFLRHLEGGCSVPVAVHTVMK

Bovine                        LDLVGVLHDPETLLRCIAERSFLRHLEGGCSVPVAVHTAIK

Slime mold                    QSILNPLIHRESMYCCEAERSMLRDLEGGCHVPIGVVTKLH

Baker's yeast                 MKILDEICDLNATICCLSERALMRTLEGGCSVPIGVESKYN

Fission yeast                 IEMLKPLQHQETLYACLAERALMKRLQGGCAIPIGVQTDVL

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 2 – 361 Porphobilinogen deaminase
Modified residue 261 – 261 S-(dipyrrolylmethanemethyl)cysteine
Alternative sequence 218 – 257 Missing. In isoform 3 and isoform 4.
Helix 241 – 257


Literature citations

Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria.
Mgone C.S.; Lanyon W.G.; Moore M.R.; Louie G.V.; Connor J.M.;
Hum. Genet. 92:619-622(1993)
Cited for: VARIANTS AIP ARG-247; THR-252 AND VAL-252;

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.