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UniProtKB/Swiss-Prot O43933: Variant p.Gly843Asp

Peroxisome biogenesis factor 1
Gene: PEX1
Variant information

Variant position:  843
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 843 (G843D, p.Gly843Asp).
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:  Peroxisome biogenesis disorder complementation group 1 (PBD-CG1) [MIM:214100]: A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). {ECO:0000269|PubMed:19105186}. 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.

Involvement in disease:  Peroxisome biogenesis disorder 1B (PBD1B) [MIM:601539]: A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. {ECO:0000269|PubMed:11439091, ECO:0000269|PubMed:16088892, ECO:0000269|PubMed:9398847, ECO:0000269|PubMed:9539740}. 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.

Involvement in disease:  Peroxisome biogenesis disorder 1A (PBD1A) [MIM:214100]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD1A is an autosomal recessive systemic disorder characterized clinically by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. {ECO:0000269|PubMed:9398847, ECO:0000269|PubMed:9398848, ECO:0000269|PubMed:9539740}. 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 PBD1A, PBD1B and PBD-CG1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  843
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1283
The length of the canonical sequence.

Location on the sequence:   PASLRSVNLHKPRDLGWDKI  G GLHEVRQILMDTIQLPAKYP
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                         PASLRSVNLHKPRDLGWDKIGGLHEVRQILMDTIQLPAKYP

Mouse                         PASLRNVNLHKPRDLGWDKIGGLHEVRQILMDTIQLPAKYP

Slime mold                    PITLKGIKLHSS-EIKWQDIGGLDSVRAMLKETIEWPTKYP

Baker's yeast                 PSALRGVKLTKETNIKWGDIGALANAKDVLLETLEWPTKYE

Fission yeast                 PLQLRKAKFVKS-SIRWIDIAGMQEAKEAVRDIIESPVKYS

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 – 1283 Peroxisome biogenesis factor 1


Literature citations

Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.
Portsteffen H.; Beyer A.; Becker E.; Epplen C.; Pawlak A.; Kunau W.-H.; Dodt G.;
Nat. Genet. 17:449-452(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT PBD1A/PBD1B ASP-843;

Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.
Reuber B.E.; Germain-Lee E.; Collins C.S.; Morrell J.C.; Ameritunga R.; Moser H.W.; Valle D.; Gould S.J.;
Nat. Genet. 17:445-448(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); VARIANT PBD1A ASP-843; VARIANT PBD1B ASP-843;

Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.
Tamura S.; Okumoto K.; Toyama R.; Shimozawa N.; Tsukamoto T.; Suzuki Y.; Osumi T.; Kondo N.; Fujiki Y.;
Proc. Natl. Acad. Sci. U.S.A. 95:4350-4355(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS PBD1A 634-GLY--HIS-690 DEL; PRO-664 AND ASP-843; VARIANTS PBD1B 634-GLY--HIS-690 DEL; PRO-664 AND ASP-843;

Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction.
Tamura S.; Matsumoto N.; Imamura A.; Shimozawa N.; Suzuki Y.; Kondo N.; Fujiki Y.;
Biochem. J. 357:417-426(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT PBD1B ASP-843;

Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.
Yik W.Y.; Steinberg S.J.; Moser A.B.; Moser H.W.; Hacia J.G.;
Hum. Mutat. 30:E467-E480(2009)
Cited for: INVOLVEMENT IN PBD-CG1; VARIANTS PBD-CG1 ARG-590; ARG-593; GLY-798; ASP-843; PRO-1008 DEL AND GLU-1237; VARIANTS MET-696 AND GLN-948;

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.