UniProtKB/SwissProt variant VAR

Variant information

Variant position:

294

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 Isoleucine (I) to Threonine (T) at position 294 (I294T, p.Ile294Thr).

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 hydrophobic (I) to medium size and polar (T)

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

Variant description:

In GILBS and CN2; 40-55% normal bilirubin glucuronidation activity; normal Km for bilirubin; when homozygous far less repressive and generates the mild Gilbert phenotype.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs72551347 [ dbSNP | Ensembl ]

Sequence information

Variant position:

294

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

Protein sequence length:

533

The length of the canonical sequence.

Location on the sequence:

FVGGINCLHQNPLSQEFEAY I NASGEHGIVVFSLGSMVSEI

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                         FVGGINCLHQNPLSQEFEAYINASGEHGIVVFSLGSMVSEI

Mouse                         FIGGINCLQKKPLSQEFEAYVNASGEHGIVVFSLGSMVSEI

Rat                           FIGGINCLQKKALSQEFEAYVNASGEHGIVVFSLGSMVSEI

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	26 – 533	UDP-glucuronosyltransferase 1A1
Glycosylation	295 – 295	N-linked (GlcNAc...) asparagine

Literature citations

Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease.
Ciotti M.; Chen F.; Rubaltelli F.F.; Owens I.S.;
Biochim. Biophys. Acta 1407:40-50(1998)
Cited for: VARIANT CN2 THR-294; CHARACTERIZATION OF VARIANT CN2 THR-294;

Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.
Kadakol A.; Ghosh S.S.; Sappal B.S.; Sharma G.; Chowdhury J.R.; Chowdhury N.R.;
Hum. Mutat. 16:297-306(2000)
Cited for: VARIANTS CN1 ASP-39; PHE-170 DEL; ARG-177; ARG-276; VAL-291; GLU-308; TRP-336; ARG-357; THR-368; PHE-375; ARG-381; SER-387; PRO-401 AND GLU-428; VARIANTS CN2 ARG-15; GLN-175; TRP-209; GLY-225 AND ARG-331; VARIANTS GILBS ARG-71; GLN-229; THR-294; GLY-367 AND ASP-486;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P22309: Variant p.Ile294Thr