NCEH1

protein-coding

neutral cholesterol ester hydrolase 1, the group of Arylacetamide deacetylase family

Gene summary

Predicted to enable serine hydrolase activity. Predicted to be involved in ether lipid metabolic process. Predicted to act upstream of or within protein dephosphorylation and xenobiotic metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2025]

Previous symbols:

AADACL1

MANE transcript

NM_020792.6

Inheritance

—

ClinVar variants

U:52B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr3:172,630,249-172,711,218

External References & Databases

Ensembl (ENSG00000144959)

Transcript & Mutation Effects

hg38 • Region Span ~81.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCEH1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020792.6. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	1 clinvar	4
missense			49 clinvar	1 clinvar	1 clinvar	51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	52	2	2	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020792.6	RefSeq	NP_065843.4	5	MANE Select
ENST00000475381.7	Ensembl	ENSP00000418571.4	5	MANE Select
NM_001146276.3	RefSeq	NP_001139748.2	5	Standard
NM_001146277.3	RefSeq	NP_001139749.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cortisol synthesis and secretion - Homo sapiens (human)
Cushing,s syndrome - Homo sapiens (human)
Bile secretion - Homo sapiens (human)
Cholesterol metabolism - Homo sapiens (human)
miR-targeted genes in lymphocytes - TarBase

Biological Process

lipid catabolic process
low-density lipoprotein particle clearance

Molecular Function

sterol esterase activity

Cellular Component

endoplasmic reticulum membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000538775
Coding exons: 5
Length: 80970
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.669	226	256	0.882	0.0000136	2909
Missense (PolyPhen)		55	93.929	0.58555		1110
Synonymous	0.176	104	106	0.978	0.00000592	930
Loss of Function	2.39	6	16.4	0.365	6.96e-7	202

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolyzes 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor. May be responsible for cholesterol ester hydrolysis in macrophages, thereby contributing to the development of atherosclerosis. Also involved in organ detoxification by hydrolyzing exogenous organophosphorus compounds. May contribute to cancer pathogenesis by promoting tumor cell migration. {ECO:0000269|PubMed:17052608}.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.738
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium