NCEH1

Chr 3

neutral cholesterol ester hydrolase 1

Also known as: AADACL1, NCEH

NCBI Gene: 57552 ENSG00000144959 UniProt: Q6PIU2 OMIM: 613234

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.72

Clinical Summary— NCEH1

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

58 VUS of 69 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.013

Z-score 2.39

OE 0.36 (0.20–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.67Z-score

OE missense 0.88 (0.79–0.98)

226 obs / 256.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.20–0.72)

0≤0.351.4

Missense OE?0.88 (0.79–0.98)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 16.4Missense obs/exp: 226 / 256.1Syn Z: 0.18

This gene — mechanism propensity

0.6746th %ile

GOF

0.5954th %ile

LOF

0.2680th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	48	10	0	58
Likely Benign	1	1	1	3
Benign	1	0	1	2
Total	50	11	2	63

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

23 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap NCEH1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →