UniProtKB/Swiss-Prot P22309: Variant p.Leu175Gln

UDP-glucuronosyltransferase 1-1
Gene: UGT1A1
Chromosomal location: 2q37
Variant information

Variant position:  175
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Leucine (L) to Glutamine (Q) at position 175 (L175Q, p.Leu175Gln).
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 (L) to medium size and polar (Q)
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 CN2; has low residual bilirubin glucuronidation activity of about 4.6% of that of the wild-type protein.
Any additional useful information about the variant.



Sequence information

Variant position:  175
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:   PCSPIVAQYLSLPTVFFLHA  L PCSLEFEATQCPNPFSYVPR
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                         PCSPIVAQYLSLPTVFFLHALPCSLEFEATQCPNPFSYVPR

Mouse                         PCGSIVAQYLTVPTVYFLNKLPCSLDSEATQCPVPLSYVPK

Rat                           PCGSIVAQYLSLPAVYFLNALPCSLDLEATQCPAPLSYVPK

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 26 – 533 UDP-glucuronosyltransferase 1-1


Literature citations

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: FUNCTION; SUBSTRATE SPECIFICITY; 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;

Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.
Seppen J.; Bosma P.J.; Goldhoorn B.G.; Bakker C.T.M.; Roy Chowdhury J.; Roy Chowdhury N.; Jansen P.L.M.; Oude Elferink R.P.J.;
J. Clin. Invest. 94:2385-2391(1994)
Cited for: VARIANTS CN1 PHE-170 DEL; ARG-177; ARG-276 AND PHE-375; VARIANTS CN2 GLN-175 AND TRP-209;

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;

Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus.
Kadakol A.; Sappal B.S.; Ghosh S.S.; Lowenheim M.; Chowdhury A.; Chowdhury S.; Santra A.; Arias I.M.; Chowdhury J.R.; Chowdhury N.R.;
J. Med. Genet. 38:244-249(2001)
Cited for: VARIANT CN2 GLN-175;

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.