UniProtKB/SwissProt variant VAR

Variant information

Variant position:

225

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 Arginine (R) to Tryptophan (W) at position 225 (R225W, p.Arg225Trp).

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 large size and basic (R) to large size and aromatic (W)

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:

Congenital bile acid synthesis defect 6 (CBAS6) [MIM:617308]: An inborn error of bile acid synthesis characterized by abnormally increased liver enzymes, hypolipidemia and low cholesterol, vitamin D deficiency, elevated plasma and urinary levels of C27 intermediate bile acids 3alpha,7alpha-dihydroxy-5beta-cholestanoic acid (DHCA) and 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid (THCA). Serum levels of phytanic and pristanic acids are normal. Clinical features include liver fibrosis, mild ataxia, delayed development, and cognitive impairment. Liver histology shows many thin fibrous septa, swollen hepatocytes, glycogenated nuclei, and focal acinar transformation, consistent with hepatocellular injury and regeneration, without signs of obvious cholestasis, cholate stasis, or steatosis. CBAS6 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:27647924, ECO:0000269|PubMed:27884763}. 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 CBAS6; reduces fatty acid beta-oxidation activity; does not alter subcellular location.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs150832314 [ dbSNP | Ensembl ]

Sequence information

Variant position:

225

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

Protein sequence length:

681

The length of the canonical sequence.

Location on the sequence:

QAQLICSGARRGMHAFIVPI R SLQDHTPLPGIIIGDIGPKM

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                         QAQLICSGARRGMHAFIVPIRSLQDHTPLPGIIIGDIGPKM

Mouse                         LAHLICLGARHGMHAFIVPIRSLEDHTPLPGITVGDIGPKM

Rat                           LAQLTCLGVRHGMHAFIVPIRSLEDHTPLPGITVGDIGPKM

Rabbit                        LAQLICSGARRGMHAFIVPVRSLQDHTPLPGITIGDIGPKM

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	1 – 681	Peroxisomal acyl-coenzyme A oxidase 2

Literature citations

ACOX2 deficiency: An inborn error of bile acid synthesis identified in an adolescent with persistent hypertransaminasemia.
Monte M.J.; Alonso-Pena M.; Briz O.; Herraez E.; Berasain C.; Argemi J.; Prieto J.; Marin J.J.;
J. Hepatol. 66:581-588(2017)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; INVOLVEMENT IN CBAS6; VARIANT CBAS6 TRP-225; CHARACTERIZATION OF VARIANT CBAS6 TRP-225;

UniProtKB/Swiss-Prot Q99424: Variant p.Arg225Trp