NM_001025195.1(CES1):c.428G>A (p.Gly143Glu) AND Carboxylesterase 1 deficiency

Clinical significance:Pathogenic (Last evaluated: Jun 1, 2008)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000019168.27

Allele description

NM_001025195.1(CES1):c.428G>A (p.Gly143Glu)

Gene:
CES1:carboxylesterase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q12.2
Genomic location:
Preferred name:
NM_001025195.1(CES1):c.428G>A (p.Gly143Glu)
HGVS:
  • NC_000016.10:g.55823661C>T
  • NG_012057.1:g.14503G>A
  • NM_001025195.1:c.428G>A
  • NP_001020366.1:p.Gly143Glu
  • NC_000016.9:g.55857573C>T
Protein change:
G143E; GLY143GLU
Links:
OMIM: 114835.0001; dbSNP: rs121912777
GMAF:
0.0002(A), 121912777
NCBI 1000 Genomes Browser:
rs121912777
Molecular consequence:
  • NM_001025195.1:c.428G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Carboxylesterase 1 deficiency
Identifiers:
MedGen: CN071470

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000039456OMIMno assertion criteria providedPathogenic
(Jun 1, 2008)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis.

Zhu HJ, Patrick KS, Yuan HJ, Wang JS, Donovan JL, DeVane CL, Malcolm R, Johnson JA, Youngblood GL, Sweet DH, Langaee TY, Markowitz JS.

Am J Hum Genet. 2008 Jun;82(6):1241-8. doi: 10.1016/j.ajhg.2008.04.015. Epub 2008 May 15.

PubMed [citation]
PMID:
18485328
PMCID:
PMC2427248

Details of each submission

From OMIM, SCV000039456.1

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

Description

In a Caucasian male of European descent participating in a study of the pharmacokinetics of methylphenidate, who displayed a highly unusual concentration-versus-time profile suggestive of a metabolic deficiency in CES1, Zhu et al. (2008) identified compound heterozygosity for a 428G-A transition in exon 4 of the CES1 gene, resulting in a gly143-to-glu (G143E) substitution, and a 1-bp deletion (780delT; 114835.0002) in exon 6 of CES1, resulting in a frameshift and premature truncation of the protein. His father was heterozygous for G143E and his mother for 780delT. The minor allele frequency of G143E was determined to be 3.7%, 4.3%, 2.0%, and 0% in white, black, Hispanic, and Asian populations, respectively; the 1-bp deletion was not found in 925 DNA samples examined. In vitro functional studies demonstrated that the catalytic functions of both G143E and 780delT are substantially impaired, with a complete loss of hydrolytic activity toward methylphenidate and only 12.4% and 0.6% catalytic efficiency, respectively, toward the more sensitive substrate p-nitrophenyl acetate.

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

Last Updated: Aug 23, 2017

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