Home  |  Contact

UniProtKB/Swiss-Prot P08397: Variant p.Arg201Trp

Porphobilinogen deaminase
Gene: HMBS
Variant information

Variant position:  201
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 Arginine (R) to Tryptophan (W) at position 201 (R201W, p.Arg201Trp).
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 (R) to large size and aromatic (W)
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

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; residual activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  201
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:   QEFSAIILATAGLQRMGWHN  R VGQILHPEECMYAVGQGALG
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                         QEFSAIILATAGLQRMGWHNRVGQILHPEECMYAVGQGALG

Mouse                         QEFSAIVLAVAGLQRMGWQNRVGQILHPEECMYAVGQGALA

Rat                           LEFSAIILAVAGLQRMGWQNRVGQILHPEECMYAVGQGALA

Bovine                        QEFSAIILATAGLQRMGWQNRVGQILHPEECMYAVGQGALG

Slime mold                    NGYDGMILAVAGLERMELTDHISEIIPDSISLYAVGQGSLG

Baker's yeast                 SPYQCIILASAGLMRMGLENRITQRFHSDTMYHAVGQGALG

Fission yeast                 SQFDCLVLAAAGLFRLGLKDRIAQMLTAPFVYYAVGQGALA

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
Helix 199 – 201


Literature citations

Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles.
Lundin G.; Wedell A.; Thunell S.; Anvret M.;
Hum. Genet. 93:59-62(1994)
Cited for: VARIANT AIP TRP-201;

Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes 'variant acute intermittent porphyria' with normal expression of the erythroid-specific enzyme.
Chen C.-H.; Astrin K.H.; Lee G.; Anderson K.E.; Desnick R.J.;
J. Clin. Invest. 94:1927-1937(1994)
Cited for: VARIANTS AIP PHE-93; TRP-116; TRP-201 AND PHE-247;

Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families.
Lundin G.; Lee J.-S.; Thunell S.; Anvret M.;
Hum. Genet. 100:63-66(1997)
Cited for: VARIANTS AIP TRP-116; LEU-119; GLN-167; TRP-167; TRP-173; TRP-201 AND ASP-216;

Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation.
De Siervi A.; Rossetti M.V.; Parera V.E.; Astrin K.H.; Aizencang G.I.; Glass I.A.; Batlle A.M.C.; Desnick R.J.;
Am. J. Med. Genet. 86:366-375(1999)
Cited for: VARIANTS AIP PRO-34; ARG-111; TRP-173; TRP-201; 329-LEU--GLN-332 DEL AND SER-335;

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.