UniProtKB/SwissProt variant VAR

Variant information

Variant position:

134

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Alanine (A) to Aspartate (D) at position 134 (A134D, p.Ala134Asp).

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 medium size and acidic (D)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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

Variant description:

In TYRSN1; loss of activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121965074 [ dbSNP | Ensembl ]

Sequence information

Variant position:

134

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:

TMHLPATIGDYTDFYSSRQH A TNVGIMFRDKENALMPNWLH

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                         TMHLPATIGDYTDFYSSRQHATNVGIMFRDKENALMPNWLH

Mouse                         TMHLPATIGDYTDFYSSRQHATNVGIMFRGKENALLPNWLH

Rat                           TMHLPATIGDYTDFYSSLQHATNVGIMFRGKENALLPNWLH

Bovine                        TMYLPATIGDYTDFYSSRHHATNVGVMFRGKENALMPNWLH

Caenorhabditis elegans        TMHLPAQIGDYTDFYSSIHHATNVGIMFRGKENALMPNWKW

Slime mold                    TMLLPARIGDYTDFYASKEHATNVGIMFRGKENALMPNWVH

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.

Type	Positions	Description
Chain	2 – 419	Fumarylacetoacetase
Active site	133 – 133	Proton acceptor
Binding site	126 – 126
Binding site	128 – 128
Binding site	142 – 142

Literature citations

Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity.
Labelle Y.; Phaneuf D.; Leclerc B.; Tanguay R.M.;
Hum. Mol. Genet. 2:941-946(1993)
Cited for: VARIANT TYRSN1 ASP-134;

Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase.
Rootwelt H.; Chou J.; Gahl W.A.; Berger R.; Coskun T.; Brodtkorb E.; Kvittingen E.A.;
Hum. Genet. 93:615-619(1994)
Cited for: VARIANTS TYRSN1 ASP-134 AND LEU-342;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16930: Variant p.Ala134Asp