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NM_000463.3(UGT1A1):c.44T>G (p.Leu15Arg) AND Crigler-Najjar syndrome, type II

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 24, 2003
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:
RCV000013081.17

Allele description [Variation Report for NM_000463.3(UGT1A1):c.44T>G (p.Leu15Arg)]

NM_000463.3(UGT1A1):c.44T>G (p.Leu15Arg)

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.44T>G (p.Leu15Arg)
HGVS:
  • NC_000002.12:g.233760331T>G
  • NG_002601.2:g.175588T>G
  • NG_033238.1:g.5059T>G
  • NM_000463.3:c.44T>GMANE SELECT
  • NM_001072.4:c.862-6703T>GMANE SELECT
  • NM_007120.3:c.868-6703T>GMANE SELECT
  • NM_019075.4:c.856-6703T>GMANE SELECT
  • NM_019076.5:c.856-6703T>GMANE SELECT
  • NM_019077.3:c.856-6703T>GMANE SELECT
  • NM_019078.2:c.868-6703T>GMANE SELECT
  • NM_019093.4:c.868-6703T>GMANE SELECT
  • NM_021027.3:c.856-6703T>GMANE SELECT
  • NM_205862.3:c.61-6703T>G
  • NP_000454.1:p.Leu15Arg
  • NP_000454.1:p.Leu15Arg
  • LRG_733t1:c.44T>G
  • LRG_733:g.5059T>G
  • LRG_733p1:p.Leu15Arg
  • NC_000002.11:g.234668977T>G
  • NM_000463.2:c.44T>G
  • P22309:p.Leu15Arg
Protein change:
L15R; LEU15ARG
Links:
UniProtKB: P22309#VAR_019410; OMIM: 191740.0023; dbSNP: rs111033541
NCBI 1000 Genomes Browser:
rs111033541
Molecular consequence:
  • NM_001072.4:c.862-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007120.3:c.868-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019075.4:c.856-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019076.5:c.856-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019077.3:c.856-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019078.2:c.868-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019093.4:c.868-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_021027.3:c.856-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_205862.3:c.61-6703T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000463.3:c.44T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Crigler-Najjar syndrome, type II
Synonyms:
HYPERBILIRUBINEMIA, CRIGLER-NAJJAR TYPE II; Crigler Najjar syndrome, type 2; Mutation in the UDP-glucuronosyl-transferase gene
Identifiers:
MONDO: MONDO:0011725; MedGen: C2931132; Orphanet: 205; OMIM: 606785

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000033327OMIM
no assertion criteria provided
Pathogenic
(Oct 24, 2003) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II.

Seppen J, Steenken E, Lindhout D, Bosma PJ, Elferink RP.

FEBS Lett. 1996 Jul 29;390(3):294-8.

PubMed [citation]
PMID:
8706880

Rapid proteasomal degradation of translocation-deficient UDP-glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type II.

Ohnishi A, Emi Y.

Biochem Biophys Res Commun. 2003 Oct 24;310(3):735-41.

PubMed [citation]
PMID:
14550264

Details of each submission

From OMIM, SCV000033327.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 2 patients with Crigler-Najjar syndrome type II (606785), Seppen et al. (1996) identified homozygosity for a leu15-to-arg (L15R) substitution in the UGT1A1 gene. The mutation was predicted to disrupt the hydrophobic core of the signal peptide. Transfection studies in COS cells found equal expression of wildtype and mutant mRNA, but the mutant protein was expressed with 0.5% efficiency compared to the wildtype protein.

In COS cells transfected with the L15R mutation, Ohnishi and Emi (2003) found that the mutant protein did not relocate across the endoplasmic reticulum membrane and was degraded rapidly with a half-life of approximately 50 minutes, in contrast to the much longer half-life of approximately 12.8 hours for the wildtype protein. The findings demonstrated that the L15R mutant protein was rapidly degraded by the proteasome owing to its mislocalization in the cell.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 1, 2024