NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln) AND Gilbert syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic; Affects (2 submissions)
Last evaluated:: May 1, 2019
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000013062.27

Allele description

NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln)

Genes:

UGT1A:UDP glucuronosyltransferase family 1 member A complex locus [Gene - HGNC]
UGT1A10:UDP glucuronosyltransferase family 1 member A10 [Gene - OMIM - HGNC]
UGT1A1:UDP glucuronosyltransferase family 1 member A1 [Gene - OMIM - HGNC]
UGT1A3:UDP glucuronosyltransferase family 1 member A3 [Gene - OMIM - HGNC]
UGT1A4:UDP glucuronosyltransferase family 1 member A4 [Gene - OMIM - HGNC]
UGT1A5:UDP glucuronosyltransferase family 1 member A5 [Gene - OMIM - HGNC]
UGT1A6:UDP glucuronosyltransferase family 1 member A6 [Gene - OMIM - HGNC]
UGT1A7:UDP glucuronosyltransferase family 1 member A7 [Gene - OMIM - HGNC]
UGT1A8:UDP glucuronosyltransferase family 1 member A8 [Gene - OMIM - HGNC]
UGT1A9:UDP glucuronosyltransferase family 1 member A9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln)

HGVS:

NC_000002.12:g.233760973C>A
NG_002601.2:g.176230C>A
NG_033238.1:g.5701C>A
NM_000463.3:c.686C>AMANE SELECT
NM_001072.4:c.862-6061C>AMANE SELECT
NM_007120.3:c.868-6061C>AMANE SELECT
NM_019075.4:c.856-6061C>AMANE SELECT
NM_019076.5:c.856-6061C>AMANE SELECT
NM_019077.3:c.856-6061C>AMANE SELECT
NM_019078.2:c.868-6061C>AMANE SELECT
NM_019093.4:c.868-6061C>AMANE SELECT
NM_021027.3:c.856-6061C>AMANE SELECT
NM_205862.3:c.61-6061C>A
NP_000454.1:p.Pro229Gln
NP_000454.1:p.Pro229Gln
LRG_733t1:c.686C>A
LRG_733:g.5701C>A
LRG_733p1:p.Pro229Gln
NC_000002.11:g.234669619C>A
NM_000463.2:c.686C>A
P22309:p.Pro229Gln

Protein change:

P229Q; PRO229GLN

Links:

UniProtKB: P22309#VAR_009505; OMIM: 191740.0010; dbSNP: rs35350960

NCBI 1000 Genomes Browser:

rs35350960

Molecular consequence:

NM_001072.4:c.862-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_007120.3:c.868-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019075.4:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019076.5:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019077.3:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019078.2:c.868-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019093.4:c.868-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_021027.3:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_205862.3:c.61-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000463.3:c.686C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Gilbert syndrome
Synonyms:: HYPERBILIRUBINEMIA I; HYPERBILIRUBINEMIA, ARIAS TYPE; Gilbert Disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007745; MedGen: C0017551; OMIM: 143500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033308	OMIM	no assertion criteria provided	Affects (Dec 1, 2007)	germline	literature only	PubMed (5) [See all records that cite these PMIDs] 1692835, 8528206, 6480579, 9621515, 18004206
SCV001156254	Difficult and Complicated Liver Diseases and Artificial Liver Center,Beijing You An Hospital, Capital Medical University	no assertion criteria provided	Pathogenic (May 1, 2019)	inherited	case-control

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033308

OMIM

no assertion criteria provided

Affects
(Dec 1, 2007)

germline

literature only

PubMed (5)
[See all records that cite these PMIDs]

SCV001156254

Difficult and Complicated Liver Diseases and Artificial Liver Center,Beijing You An Hospital, Capital Medical University

no assertion criteria provided

Pathogenic
(May 1, 2019)

inherited

case-control

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
Chinese	inherited	unknown	13	not provided	not provided	not provided	not provided	case-control

Citations

PubMed

The cDNA sequence and expression of a variant 17 beta-hydroxysteroid UDP-glucuronosyltransferase.

Mackenzie PI.

J Biol Chem. 1990 May 25;265(15):8699-703.

PubMed [citation]

PMID:: 1692835

Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase.

Koiwai O, Nishizawa M, Hasada K, Aono S, Adachi Y, Mamiya N, Sato H.

Hum Mol Genet. 1995 Jul;4(7):1183-6.

PubMed [citation]

PMID:: 8528206

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000033308.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (5)

Description

This variant has been designated UGT1A1*27 (Mackenzie et al., 1997).

In affected members of 2 presumably unrelated Japanese families with Gilbert syndrome (143500), Koiwai et al. (1995) identified a heterozygous 686C-A transversion in the UGT1A gene, resulting in a pro229-to-gln (P229Q) substitution. Expression studies in COS cells demonstrated approximately 14% of normal UGT activity, whereas enzymatic activity in the patient was approximately 30% of normal, suggesting a dominant-negative effect. Since, according to Peters et al. (1984), UGT exists as a tetramer on the luminal surface of the endoplasmic reticulum, the reduced level of UGT activity in the patient with Gilbert syndrome may be explained by the random formation of complexes of mutated UGT subunits and normally active UGT subunits on the endoplasmic reticulum.

In a patient with Crigler-Najjar syndrome type II (606785), Yamamoto et al. (1998) identified a complex genotype consisting of heterozygosity for the P229Q mutation and homozygosity for a 2-bp insertion mutation (191740.0011).

Udomuksorn et al. (2007) found that the P229Q mutant protein reduced the in vitro clearance for total bilirubin glucuronidation by 70% by increasing Km and decreasing Vmax. The magnitude of decreases in clearance for other substrates varied according to substrate.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Difficult and Complicated Liver Diseases and Artificial Liver Center,Beijing You An Hospital, Capital Medical University, SCV001156254.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Chinese	13	not provided	not provided	case-control	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	unknown	not provided	not provided	not provided		13	not provided	not provided	not provided

Last Updated: Jun 18, 2022

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