Home  |  Contact

UniProtKB/Swiss-Prot P08397: Variant p.Arg26Cys

Porphobilinogen deaminase
Gene: HMBS
Variant information

Variant position:  26
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 Cysteine (C) at position 26 (R26C, p.Arg26Cys).
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 medium size and polar (C)
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; less than 1% of wild-type deaminase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  26
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:   NAAATAEENSPKMRVIRVGT  R KSQLARIQTDSVVATLKASY
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                         NAAATAEENSPKMRVIRVGTRKSQLARIQTDSVVATLKASY

Mouse                         GAATTAEENGSKMRVIRVGTRKSQLARIQTDTVVAMLKALY

Rat                           GAATTAEENGSMMRVIRVGTRKSQLARIQTDTVVAMLKTLY

Bovine                        NAAAIAEEDTPKMRVIRVGTRKSQLARIQTDSVVATLKALY

Slime mold                    ------MSSITKRDKVIIGSRKSQLAMLQTEWVRDRIQELN

Baker's yeast                 --------MGP--ETLHIGGRKSKLAVIQSNHVLKLIEEKY

Fission yeast                 ---------MPSCTSFPIGTRKSKLAVIQSEIIREELEKHY

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 15 – 15 Phosphoserine
Beta strand 20 – 28


Literature citations

Structural insight into acute intermittent porphyria.
Song G.; Li Y.; Cheng C.; Zhao Y.; Gao A.; Zhang R.; Joachimiak A.; Shaw N.; Liu Z.J.;
FASEB J. 23:396-404(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS); PROSTHETIC GROUP AT CYS-261;

Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations.
Whatley S.D.; Woolf J.R.; Elder G.H.;
Hum. Genet. 104:505-510(1999)
Cited for: VARIANTS AIP CYS-22; CYS-26; HIS-26; PRO-31; SER-42; ASN-61; ARG-85; GLY-90; ARG-111; GLN-173; TRP-173; ARG-177; CYS-195; ASP-219; ARG-247 AND ILE-269;

New mutations of the hydroxymethylbilane synthase gene in German patients with acute intermittent porphyria.
Gross U.; Puy H.; Doss M.; Robreau A.-M.; Nordmann Y.; Doss M.O.; Deybach J.-C.;
Mol. Cell. Probes 13:443-447(1999)
Cited for: VARIANTS AIP CYS-26 AND LEU-202;

Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene.
Floderus Y.; Shoolingin-Jordan P.M.; Harper P.;
Clin. Genet. 62:288-297(2002)
Cited for: VARIANTS AIP CYS-26; HIS-26; VAL-86; PRO-92; GLY-99; ARG-111; THR-113; GLN-173; ASN-178; GLN-225; GLY-225; TYR-256; ASP-260 AND PRO-343;

Acute intermittent porphyria--impact of mutations found in the hydroxymethylbilane synthase gene on biochemical and enzymatic protein properties.
Ulbrichova D.; Hrdinka M.; Saudek V.; Martasek P.;
FEBS J. 276:2106-2115(2009)
Cited for: VARIANTS AIP CYS-26; HIS-26; GLN-173; LYS-204 AND ASP-250; CHARACTERIZATION OF VARIANTS AIP CYS-26; HIS-26; GLN-173; LYS-204 AND ASP-250;

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.