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UniProtKB/Swiss-Prot O76031: Variant p.Gly298Asp

ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
Gene: CLPX
Chromosomal location: 15q22.31
Variant information

Variant position:  298
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 Glycine (G) to Aspartate (D) at position 298 (G298D, p.Gly298Asp).
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 glycine (G) to medium size and acidic (D)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Protoporphyria, erythropoietic, 2 (EPP2) [MIM:618015]: An autosomal dominant form of porphyria with onset in infancy. 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. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals. {ECO:0000269|PubMed:28874591}. Note=The disease may be 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 EPP2; results in decreased ATP hydrolysis; cells with the mutant protein show increased ALA levels and accumulation of the heme biosynthesis intermediate protoporphyrin IX.
Any additional useful information about the variant.



Sequence information

Variant position:  298
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  633
The length of the canonical sequence.

Location on the sequence:   SHDDIKLEKSNILLLGPTGS  G KTLLAQTLAKCLDVPFAICD
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                         SHDDIKLEKSNILLLGPTGSGKTLLAQTLAKCLDVPFAICD

Mouse                         SQDDIKLEKSNILLLGPTGSGKTLLAQTLAKCLDVPFAICD

Rat                           PHDDIKLEKSNILLLGPTGSGKTLLAQTLAKCLDVPFAICD

Baker's yeast                 --EDLELSKSNVLVVGPSGSGKTLLATTLAKILNVPIAITD

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 57 – 633 ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
Nucleotide binding 294 – 301 ATP


Literature citations

Mutation in human CLPX elevates levels of delta-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria.
Yien Y.Y.; Ducamp S.; van der Vorm L.N.; Kardon J.R.; Manceau H.; Kannengiesser C.; Bergonia H.A.; Kafina M.D.; Karim Z.; Gouya L.; Baker T.A.; Puy H.; Phillips J.D.; Nicolas G.; Paw B.H.;
Proc. Natl. Acad. Sci. U.S.A. 114:E8045-E8052(2017)
Cited for: INVOLVEMENT IN EPP2; FUNCTION; VARIANT EPP2 ASP-298; CHARACTERIZATION OF VARIANT EPP2 ASP-298;

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.