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UniProtKB/Swiss-Prot P06132: Variant p.Ala80Gly

Uroporphyrinogen decarboxylase
Gene: UROD
Variant information

Variant position:  80
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 Glycine (G) at position 80 (A80G, p.Ala80Gly).
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 glycine (G)
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:  Hepatoerythropoietic porphyria (HEP) [MIM:176100]: 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. HEP is a cutaneous porphyria that presents in infancy. It is characterized biochemically by excessive excretion of acetate-substituted porphyrins and accumulation of protoporphyrin in erythrocytes. Uroporphyrinogen decarboxylase levels are very low in erythrocytes and cultured skin fibroblasts. {ECO:0000269|PubMed:12071824, ECO:0000269|PubMed:15491440, ECO:0000269|PubMed:1634232, ECO:0000269|PubMed:17240319, ECO:0000269|PubMed:1905636, ECO:0000269|PubMed:21668429, ECO:0000269|PubMed:3775362, ECO:0000269|PubMed:8176248, ECO:0000269|PubMed:8644733, ECO:0000269|PubMed:8896428}. 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 HEP.
Any additional useful information about the variant.

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



Sequence information

Variant position:  80
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  367
The length of the canonical sequence.

Location on the sequence:   RSPEACCELTLQPLRRFPLD  A AIIFSDILVVPQALGMEVTM
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                         RSPEACCELTLQPLRRFP--LDAAIIFSDILVVPQALGMEVTM

Mouse                         RSPEACCELTLQPLRRFP--LDAAIIFSDILVVPQALGMEV

Sheep                         RSPEACCELTLQPLRRFP--LDAAIIFSDILVVPQALGMEV

Zebrafish                     RSPEACCELTLQPLRRFP--FDAAIIFSDILVVPQAMGMEV

Drosophila                    RTPELACEVTMQPLRRFD--LDASIIFSDILVIPQALGLTV

Slime mold                    RTPELACKVTLQPLDRFP--LDAAIIFSDILVVPQAMGIEV

Baker's yeast                 RDAEIASEITIQPVRRYRGLIDAAIIFSDILVIPQAMGMRV

Fission yeast                 QTPETACELTLQPVTRFKGLLDAAIIFSDILVIPQALGMQV

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 – 367 Uroporphyrinogen decarboxylase
Binding site 85 – 85 Substrate
Binding site 86 – 86 Substrate
Site 86 – 86 Transition state stabilizer
Mutagenesis 86 – 86 D -> E. 5-10% of wild-type activity.
Mutagenesis 86 – 86 D -> G. Very low activity. Binds substrate with similar geometry as wild-type.
Mutagenesis 86 – 86 D -> N. No activity. Unable to bind substrate.


Literature citations

Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria.
McManus J.F.; Begley C.G.; Sassa S.; Ratnaike S.;
Blood 88:3589-3600(1996)
Cited for: VARIANT HEP GLY-80; VARIANTS FPCT GLN-253; ARG-318 AND THR-334;

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.