GeneBe

BCHE

protein-coding

butyrylcholinesterase

Gene summary

This gene encodes a cholinesterase enzyme and member of the type-B carboxylesterase/lipase family of proteins. The encoded enzyme exhibits broad substrate specificity and is involved in the detoxification of poisons including organophosphate nerve agents and pesticides, and the metabolism of drugs including cocaine, heroin and aspirin. Humans homozygous for certain mutations in this gene exhibit prolonged apnea after administration of the muscle relaxant succinylcholine. [provided by RefSeq, Jul 2016]

Previous symbols:
  • CHE1
  • CHE2

MANE transcript

NM_000055.4

Inheritance

AR

ClinVar variants

P:75U:125B:19

Top phenotype

Butyrlcholinesterase deficiency

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr3:165,772,904-165,837,462

External References & Databases

Ensembl (ENSG00000114200)NCBI Gene (590)OMIM (177400)HGNC:983GenCCUniProt (P06276)AlphaFoldClinVar (BCHE)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~64.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

butyrylcholinesterase deficiencyDEFINITIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0015270

Submitter: Ambry Genetics

butyrylcholinesterase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015270

Submitter: Labcorp Genetics (formerly Invitae)

butyrylcholinesterase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015270

Submitter: Ambry Genetics

butyrylcholinesterase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015270

Submitter: PanelApp Australia

butyrylcholinesterase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015270

Submitter: Orphanet

butyrylcholinesterase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015270

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Butyrlcholinesterase deficiencyAR

Manifestation: Biochemical

Intervention: Pharmacogenomic

Rationale: Individuals have prolonged apnea upon use of specific anesthetics (ie, suxamethonium, succinylcholine)

Refs: 13711731; 14465122; 4984470; 3741370; 3225823; 2915989; 2911599; 2013061; 1662391; 1349196; 1415224; 8554068; 9543549; 9302273; 9110359; 9388484; 10190327; 10699053; 12881446; 16788378; 18075469; 18555211; 21029050Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCHE variants in ClinVar

15 Conditions Cataloged
Deficiency of butyrylcholinesteraseTotal: 109
Inborn genetic diseasesTotal: 83
not providedTotal: 37
BCHE-related disorderTotal: 23
not specifiedTotal: 21
Autosomal recessive BCHE-related disordersTotal: 2
BCHE, J variantTotal: 1
BCHE, fluoride 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000055.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
10
clinvar
 17
missense
4
clinvar
14
clinvar
112
clinvar
9
clinvar
 139
nonsense
2
clinvar
23
clinvar
2
clinvar
 27
start loss
1
clinvar
 1
frameshift
6
clinvar
22
clinvar
2
clinvar
 30
splice donor/acceptor (+/-2bp)
4
clinvar
1
clinvar
 5
Total1263125190219

Highest pathogenic variant AF is 0.016023481

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000055.4RefSeqNP_000046.13MANE Select
ENST00000264381.8EnsemblENSP00000264381.33MANE Select
ENST00000479451.5EnsemblENSP00000418325.13Standard
ENST00000482958.1EnsemblENSP00000419804.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Irinotecan Pathway, Pharmacokinetics
  • Irinotecan Pathway, Pharmacodynamics
  • Heroin Metabolism Pathway
  • Irinotecan Action Pathway
  • Heroin Action Pathway

Biological Process

  • learning
  • negative regulation of cell population proliferation
  • neuroblast differentiation
  • choline metabolic process
  • response to alkaloid

Molecular Function

  • amyloid-beta binding
  • catalytic activity
  • acetylcholinesterase activity
  • cholinesterase activity
  • hydrolase activity, acting on ester bonds

Cellular Component

  • extracellular region
  • nuclear envelope lumen
  • endoplasmic reticulum lumen
  • membrane
  • blood microparticle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000264381
Coding exons
3
Length
64569
Individuals with no LoFs
125436
Homozygous LoFs
1
Heterozygous LoFs
301
Defined
125738
p
0.00120
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.043673151.160.00001523975
Missense (PolyPhen)139113.991.21951409
Synonymous0.1281071090.9840.000005361125
Loss of Function0.3412122.80.9230.00000120283

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000630.00062rare
Latino/Admixed American0.00110.0011notable
Ashkenazi Jewish0.00510.0051notable
East Asian0.00290.0029notable
Finnish00.0absent
European (Non-Finnish)0.000870.00085rare
South Asian0.00150.0015notable
Other0.00130.0013notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters. {ECO:0000269|PubMed:19452557, ECO:0000269|PubMed:19542320}.;
Disease
DISEASE: Butyrylcholinesterase deficiency (BCHED) [MIM:617936]: An autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency. {ECO:0000269|PubMed:10404729, ECO:0000269|PubMed:11928765, ECO:0000269|PubMed:12881446, ECO:0000269|PubMed:1306123, ECO:0000269|PubMed:1349196, ECO:0000269|PubMed:1415224, ECO:0000269|PubMed:15563885, ECO:0000269|PubMed:15781196, ECO:0000269|PubMed:1611188, ECO:0000269|PubMed:16788378, ECO:0000269|PubMed:17700357, ECO:0000269|PubMed:18075469, ECO:0000269|PubMed:18300943, ECO:0000269|PubMed:25054547, ECO:0000269|PubMed:25264279, ECO:0000269|PubMed:2915989, ECO:0000269|PubMed:7634491, ECO:0000269|PubMed:8554068, ECO:0000269|PubMed:8680411, ECO:0000269|PubMed:9110359, ECO:0000269|PubMed:9191541, ECO:0000269|PubMed:9388484, ECO:0000269|PubMed:9543549, ECO:0000269|PubMed:9694584}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.505

Intolerance Scores

LoFtool
0.416
RVIS EVS
0.78
RVIS percentile EVS
87.21

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.536

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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