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UniProtKB/Swiss-Prot P16930: Variant p.Asp233Val

Fumarylacetoacetase
Gene: FAH
Chromosomal location: 15q23-q25
Variant information

Variant position:  233
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 Aspartate (D) to Valine (V) at position 233 (D233V, p.Asp233Val).
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 medium size and acidic (D) to medium size and hydrophobic (V)
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:  Tyrosinemia 1 (TYRSN1) [MIM:276700]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and hepatorenal manifestations. Typical features include hepatic necrosis, renal tubular injury, episodic weakness, self-mutilation, and seizures. Renal tubular dysfunction is associated with phosphate loss and hypophosphataemic rickets. Progressive liver disease can lead to the development of hepatocellular carcinoma. Dietary treatment with restriction of tyrosine and phenylalanine alleviates the rickets, but liver transplantation has so far been the only definite treatment. {ECO:0000269|PubMed:11196105, ECO:0000269|PubMed:11278491, ECO:0000269|PubMed:11476670, ECO:0000269|PubMed:1401056, ECO:0000269|PubMed:20003495, ECO:0000269|PubMed:7550234, ECO:0000269|PubMed:7757089, ECO:0000269|PubMed:7942842, ECO:0000269|PubMed:7977370, ECO:0000269|PubMed:8005583, ECO:0000269|PubMed:8318997, ECO:0000269|PubMed:8364576, ECO:0000269|PubMed:8557261, ECO:0000269|PubMed:9633815}. 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 TYRSN1; loss of activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  233
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  419
The length of the canonical sequence.

Location on the sequence:   GEPIPISKAHEHIFGMVLMN  D WSARDIQKWEYVPLGPFLGK
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                         GEPIPISKAHEHIFGMVLMNDWSARDIQKWEYVPLGPFLGK

Mouse                         GEPIPISKAHEHIFGMVLMNDWSARDIQQWEYVPLGPFLGK

Rat                           GEPIPISKAQEHIFGMVLMNDWSARDIQQWEYVPLGPFLGK

Bovine                        GEPIPISKAHEHIFGMVLMNDWSARDIQKWEYVPLGPFLGK

Slime mold                    GEPISIESAKDHIFGLVLLNDWSARDIQKWEYVPLGPFLAK

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 – 419 Fumarylacetoacetase
Metal binding 233 – 233 Calcium
Metal binding 233 – 233 Magnesium
Metal binding 253 – 253 Magnesium
Binding site 240 – 240 Substrate
Binding site 244 – 244 Substrate


Literature citations

Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1.
Rootwelt H.; Berger R.; Gray G.; Kelly D.A.; Coskun T.; Kvittingen E.A.;
Am. J. Hum. Genet. 55:653-658(1994)
Cited for: VARIANT TYRSN1 VAL-233;

Structural and functional analysis of missense mutations in fumarylacetoacetate hydrolase, the gene deficient in hereditary tyrosinemia type 1.
Bergeron A.; D'Astous M.; Timm D.E.; Tanguay R.M.;
J. Biol. Chem. 276:15225-15231(2001)
Cited for: CHARACTERIZATION OF VARIANTS TYRSN1 ILE-16; CYS-62; ASP-134; ARG-193; VAL-233; GLY-234 AND ARG-279; CHARACTERIZATION OF VARIANT TRP-341;

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.