Butyrylcholinesterase deficiency

Summary

Butyrylcholinesterase deficiency (MONDO:0015270) is a disease caused by BCHE (GenCC Definitive), with 2 cohort genes and 6 clinical trials. Top therapeutic interventions include rocuronium and azd-8848.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: BCHE (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 118
• Phenotypes (HPO): 9
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0002878	Respiratory failure	Frequent (30-79%)
HP:0001392	Abnormality of the liver	Very rare (<1-4%)
HP:0001635	Congestive heart failure	Very rare (<1-4%)
HP:0001658	Myocardial infarction	Very rare (<1-4%)
HP:0002664	Neoplasm	Very rare (<1-4%)
HP:0003470	Paralysis	Very rare (<1-4%)
HP:0004887	Respiratory failure requiring assisted ventilation	Very rare (<1-4%)
HP:0031035	Chronic infection	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	butyrylcholinesterase deficiency
Mondo ID	MONDO:0015270
MeSH	C537417
OMIM	617936
Orphanet	132
ICD-11	581237559
SNOMED CT	191397007
UMLS	C1283400
MedGen	220923
GARD	0007482
Is cancer (heuristic)	no

Also known as: apnea, postanesthetic · apnea, postanesthetic, susceptibility to, due to BCHE deficiency · BCHED · butyrylcholinesterase deficiency · cholinesterase 2 deficiency · pseudocholinesterase deficiency · pseudocholinesterase E1 · succinylcholine sensitivity · Suxamethonium sensitivity

Data availability: 118 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of biogenic amine metabolism and transport › metabolic disease involving other neurotransmitter deficiency › butyrylcholinesterase deficiency

Related subtypes (2): folinic acid-responsive seizures, hereditary hyperekplexia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

118 retrieved; paginated sample, class counts are floors:

40 likely pathogenic, 40 uncertain significance, 16 conflicting classifications of pathogenicity, 10 pathogenic, 8 pathogenic/likely pathogenic, 2 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13215	NM_000055.2(BCHE):c.293A>G (p.Asp98Gly)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13216	NM_000055.4(BCHE):c.435delinsAG (p.Phe146fs)	BCHE	Pathogenic	criteria provided, multiple submitters, no conflicts
13225	NM_000055.4:c.1160_1161ins[N[342];1146_1160]	BCHE	Pathogenic	no assertion criteria provided
13226	NM_000055.4(BCHE):c.1072T>A (p.Leu358Ile)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13227	NM_000055.4(BCHE):c.467A>G (p.Tyr156Cys)	BCHE	Pathogenic	no assertion criteria provided
13228	NM_000055.4(BCHE):c.1004T>C (p.Leu335Pro)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324370	NM_000055.4(BCHE):c.1354C>T (p.Arg452Ter)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324374	NM_000055.4(BCHE):c.1129G>T (p.Glu377Ter)	BCHE	Pathogenic	criteria provided, single submitter
225301	NM_000055.4(BCHE):c.1177G>C (p.Gly393Arg)	BCHE	Pathogenic	criteria provided, multiple submitters, no conflicts
2437111	NM_000055.4(BCHE):c.522_537del (p.Asn173_Tyr174insTer)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2682418	NM_000055.4(BCHE):c.777G>A (p.Trp259Ter)	BCHE	Pathogenic	criteria provided, single submitter
344097	NM_000055.4(BCHE):c.428G>A (p.Gly143Asp)	BCHE	Pathogenic	criteria provided, multiple submitters, no conflicts
370302	NM_000055.4(BCHE):c.1027dup (p.Thr343fs)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551265	NM_000055.4(BCHE):c.1240C>T (p.Arg414Cys)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
552544	NM_000055.4(BCHE):c.382C>T (p.Pro128Ser)	BCHE	Pathogenic	criteria provided, single submitter
555346	NM_000055.4(BCHE):c.1584T>A (p.Tyr528Ter)	BCHE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
594478	NM_000055.4(BCHE):c.100del (p.Ile34fs)	BCHE	Pathogenic	criteria provided, multiple submitters, no conflicts
210585	NM_001367721.1(CASK):c.2392C>T (p.Gln798Ter)	CASK	Pathogenic	criteria provided, single submitter
13217	NM_000055.4(BCHE):c.508G>A (p.Val170Met)	BCHE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323972	NM_000055.4(BCHE):c.1158del (p.Pro387fs)	BCHE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323974	NM_000055.4(BCHE):c.824_827dup (p.Lys276delinsAsnTer)	BCHE	Likely pathogenic	criteria provided, single submitter
1677196	NM_000055.4(BCHE):c.594T>G (p.Asp198Glu)	BCHE	Likely pathogenic	criteria provided, single submitter
2437005	NM_000055.4(BCHE):c.932_935dup (p.Pro313fs)	BCHE	Likely pathogenic	criteria provided, single submitter
2501206	NM_000055.4(BCHE):c.1171_1174dup (p.Phe392Ter)	BCHE	Likely pathogenic	criteria provided, single submitter
370179	NM_000055.4(BCHE):c.666_667del (p.Phe223fs)	BCHE	Likely pathogenic	no assertion criteria provided
370346	NM_000055.4(BCHE):c.895G>T (p.Glu299Ter)	BCHE	Likely pathogenic	no assertion criteria provided
370364	NM_000055.4(BCHE):c.793del (p.Tyr265fs)	BCHE	Likely pathogenic	criteria provided, single submitter
370388	NM_000055.4(BCHE):c.1073dup (p.Leu358fs)	BCHE	Likely pathogenic	no assertion criteria provided
370431	NM_000055.4(BCHE):c.1528G>T (p.Glu510Ter)	BCHE	Likely pathogenic	no assertion criteria provided
370446	NM_000055.4(BCHE):c.1684+1G>T	BCHE	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BCHE	Definitive	Unknown	butyrylcholinesterase deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCHE	Orphanet:132	Hereditary butyrylcholinesterase deficiency
CASK	Orphanet:163937	X-linked intellectual disability, Najm type
CASK	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
CASK	Orphanet:777	X-linked non-syndromic intellectual disability

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BCHE	HGNC:983	ENSG00000114200	P06276	Cholinesterase	gencc,clinvar
CASK	HGNC:1497	ENSG00000147044	O14936	Peripheral plasma membrane protein CASK	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCHE	Cholinesterase	Esterase with broad substrate specificity.
CASK	Peripheral plasma membrane protein CASK	Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCHE	Enzyme (other)	yes	3.1.1.8	Cholinesterase, CarbesteraseB, AChE_tetra
CASK	Kinase	yes	2.7.11.1	Prot_kinase_dom, SH3_domain, PDZ

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
parietal pleura	1
right lobe of liver	1
buccal mucosa cell	1
cortical plate	1
hair follicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCHE	237	broad	marker	parietal pleura, adrenal tissue, right lobe of liver
CASK	284	ubiquitous	marker	buccal mucosa cell, hair follicle, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CASK	4,223
BCHE	2,414

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCHE	P06276	109
CASK	O14936	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neurotransmitter clearance	1	634.4×	0.009	BCHE
Synthesis, secretion, and deacylation of Ghrelin	1	300.5×	0.009	BCHE
Dopamine Neurotransmitter Release Cycle	1	248.3×	0.009	CASK
Nephrin family interactions	1	237.9×	0.009	CASK
Syndecan interactions	1	211.5×	0.009	CASK
Synthesis of PC	1	203.9×	0.009	BCHE
Aspirin ADME	1	158.6×	0.010	BCHE
Assembly and cell surface presentation of NMDA receptors	1	126.9×	0.011	CASK
Sensory processing of sound by outer hair cells of the cochlea	1	102.0×	0.011	CASK
Neurexins and neuroligins	1	98.5×	0.011	CASK
Sensory processing of sound by inner hair cells of the cochlea	1	81.6×	0.012	CASK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
acetylcholine catabolic process	1	4213.0×	0.002	BCHE
cocaine catabolic process	1	4213.0×	0.002	BCHE
negative regulation of cellular response to growth factor stimulus	1	4213.0×	0.002	CASK
choline metabolic process	1	2808.7×	0.002	BCHE
response to folic acid	1	1203.7×	0.004	BCHE
neuroblast differentiation	1	1053.2×	0.004	BCHE
negative regulation of synaptic transmission	1	842.6×	0.004	BCHE
response to alkaloid	1	766.0×	0.004	BCHE
negative regulation of wound healing	1	648.1×	0.004	CASK
peptide hormone processing	1	468.1×	0.004	BCHE
positive regulation of calcium ion import	1	468.1×	0.004	CASK
negative regulation of cell-matrix adhesion	1	443.5×	0.004	CASK
calcium ion import	1	401.2×	0.004	CASK
regulation of neurotransmitter secretion	1	383.0×	0.004	CASK
negative regulation of keratinocyte proliferation	1	351.1×	0.005	CASK
regulation of synaptic vesicle exocytosis	1	227.7×	0.007	CASK
response to glucocorticoid	1	162.0×	0.009	BCHE
learning	1	140.4×	0.009	BCHE
establishment of localization in cell	1	80.2×	0.016	CASK
xenobiotic metabolic process	1	74.6×	0.016	BCHE
intracellular protein localization	1	52.3×	0.022	CASK
negative regulation of cell population proliferation	1	21.1×	0.051	BCHE
cell adhesion	1	18.7×	0.055	CASK
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CASK

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BCHE	PYRIDOSTIGMINE
CASK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCHE	36	4
CASK	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRIDOSTIGMINE	4	BCHE
ETHOPROPAZINE HYDROCHLORIDE	4	BCHE
RIVASTIGMINE TARTRATE	4	BCHE
ETHOPROPAZINE	4	BCHE
QUINIDINE	4	BCHE
TACRINE HYDROCHLORIDE	4	BCHE
DONEPEZIL HYDROCHLORIDE	4	BCHE
NEOSTIGMINE METHYLSULFATE	4	BCHE
NEOSTIGMINE	4	BCHE
BERBERINE	4	BCHE
PHYSOSTIGMINE SALICYLATE	4	BCHE
DONEPEZIL	4	BCHE
RIVASTIGMINE	4	BCHE
GALANTAMINE	4	BCHE
RESERPINE	4	BCHE
PYRIDOSTIGMINE BROMIDE	4	BCHE
RASAGILINE	4	BCHE
PHYSOSTIGMINE	4	BCHE
TACRINE	4	BCHE
FEDRATINIB	4	CASK
RUXOLITINIB	4	CASK
BOSUTINIB	4	CASK
CRIZOTINIB	4	CASK
SACCHARIN	3	BCHE
QUERCETIN	3	BCHE
EBSELEN	3	BCHE
BAMBUTEROL	3	BCHE
LATREPIRDINE	3	BCHE
LESTAURTINIB	3	CASK
GANSTIGMINE	2	BCHE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BCHE	1,172	Binding:1162, ADMET:9, Functional:1
CASK	92	Binding:92

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BCHE	3.1.1.8	cholinesterase
CASK	2.7.11.1, 2.7.4.8	non-specific serine/threonine protein kinase, guanylate kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BCHE	1,172

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PYRIDOSTIGMINE	4	BCHE
ETHOPROPAZINE HYDROCHLORIDE	4	BCHE
RIVASTIGMINE TARTRATE	4	BCHE
ETHOPROPAZINE	4	BCHE
QUINIDINE	4	BCHE
TACRINE HYDROCHLORIDE	4	BCHE
DONEPEZIL HYDROCHLORIDE	4	BCHE
NEOSTIGMINE METHYLSULFATE	4	BCHE
NEOSTIGMINE	4	BCHE
BERBERINE	4	BCHE
PHYSOSTIGMINE SALICYLATE	4	BCHE
DONEPEZIL	4	BCHE
RIVASTIGMINE	4	BCHE
GALANTAMINE	4	BCHE
RESERPINE	4	BCHE
PYRIDOSTIGMINE BROMIDE	4	BCHE
RASAGILINE	4	BCHE
PHYSOSTIGMINE	4	BCHE
TACRINE	4	BCHE
FEDRATINIB	4	CASK
RUXOLITINIB	4	CASK
BOSUTINIB	4	CASK
CRIZOTINIB	4	CASK
SACCHARIN	3	BCHE
QUERCETIN	3	BCHE
EBSELEN	3	BCHE
BAMBUTEROL	3	BCHE
LATREPIRDINE	3	BCHE
LESTAURTINIB	3	CASK
GANSTIGMINE	2	BCHE

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BCHE, CASK
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01205867	PHASE1	COMPLETED	Study to Investigate the Safety and Tolerability of AZD8848 in Butyrylcholinesterase Deficient Subjects
NCT06707532	Not specified	RECRUITING	The Potential Protective Effect of Using Muscle Relaxants During Electroporation Ablation (PFA)
NCT03290859	Not specified	COMPLETED	Race-Specific Propofol Titration to Effect for Procedural Sedation
NCT03415607	Not specified	UNKNOWN	Comparison on Succinylcholine Onset Time Assessed by Train of Four Stimulation Versus Clinical Judgment During Rapid Sequence Induction of Anesthesia
NCT03843580	Not specified	COMPLETED	Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) Could Decrease the Incidence of Oxygen Desaturation During Suspension Laryngoscopy: a Randomized Controlled Trial (Optilaryngo)
NCT05550584	Not specified	COMPLETED	High Flow Oxygen During Operative Hysteroscopy.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ROCURONIUM	4	1
AZD-8848	2	1