UniProtKB/Swiss-Prot P22309: Variant p.Tyr486Asp

UDP-glucuronosyltransferase 1A1
Gene: UGT1A1
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Variant information Variant position:

486 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 Tyrosine (Y) to Aspartate (D) at position 486 (Y486D, p.Tyr486Asp). 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 aromatic (Y) to medium size and acidic (D) 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
Variant description:

In CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs34993780 [ dbSNP | Ensembl ]

Sequence information Variant position:

486 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:

MRHKGAPHLRPAAHDLTWYQ Y HSLDVIGFLLAVVLTVAFIT 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                         MRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFIT

Mouse                         MRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAIVLTVVFIV

Rat                           MRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAIVLTVVFIV

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
Alternative sequence	435 – 533	SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGRQM. In isoform 2.
Mutagenesis	486 – 486	Y -> D. Decreased SN-38 glucuronosyltransferase activity.

Literature citations
Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates.
Udomuksorn W.; Elliot D.J.; Lewis B.C.; Mackenzie P.I.; Yoovathaworn K.; Miners J.O.;
Pharmacogenet. Genomics 17:1017-1029(2007)
Cited for: FUNCTION (ISOFORM 1); CATALYTIC ACTIVITY; KINETIC PARAMETERS; SUBSTRATE SPECIFICITY; CHARACTERIZATION OF VARIANTS CN2 ARG-71; LEU-83; GLN-229 AND ASP-486; Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II.
Aono S.; Yamada Y.; Keino H.; Hanada N.; Nakagawa T.; Sasaoka Y.; Yazawa T.; Sato H.; Koiwai O.;
Biochem. Biophys. Res. Commun. 197:1239-1244(1993)
Cited for: VARIANTS CN2 ARG-71 AND ASP-486; Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II.
Yamamoto K.; Soeda Y.; Kamisako T.; Hosaka H.; Fukano M.; Sato H.; Fujiyama Y.; Dachi Y.; Satoh Y.; Bamba T.;
J. Hum. Genet. 43:111-114(1998)
Cited for: VARIANTS CN2 ARG-71; TRP-209; GLN-229 AND ASP-486; Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of bilirubin UDP-glucuronosyltransferase gene.
Maruo Y.; Sato H.; Yamano T.; Doida Y.; Shimada M.;
J. Pediatr. 132:1045-1047(1998)
Cited for: VARIANT GILBS ASP-486; 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; Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate-glucuronosyltransferase gene.
Maruo Y.; Nishizawa K.; Sato H.; Sawa H.; Shimada M.;
Pediatrics 106:E59-E59(2000)
Cited for: VARIANTS HBLRTFN ARG-71 AND ASP-486; Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants.
Sneitz N.; Bakker C.T.; de Knegt R.J.; Halley D.J.; Finel M.; Bosma P.J.;
Hum. Mutat. 31:52-59(2010)
Cited for: VARIANT CN1 THR-402; VARIANTS CN2 ARG-15; ARG-71; PHE-191; TRP-209; TRP-336; HIS-387; PRO-443 AND ASP-486; CHARACTERIZATION OF VARIANT CN1 THR-402; CHARACTERIZATION OF VARIANTS CN2 ARG-71; GLN-175; PHE-191; TRP-209; ARG-331; TRP-336; HIS-387; VAL-395 AND PRO-443; CATALYTIC ACTIVITY; FUNCTION; SUBSTRATE SPECIFICITY;

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.