NCEH1

Summary

NCEH1 (neutral cholesterol ester hydrolase 1, HGNC:29260) is a protein-coding gene on chromosome 3q26.31, encoding Neutral cholesterol ester hydrolase 1 (Q6PIU2). Hydrolyzes 2-acetyl monoalkylglycerol ether (1-O-alkyl-2-acetyl-sn-glycerol), the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor.

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.

Source: NCBI Gene 57552 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• MANE Select transcript: NM_020792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29260
Approved symbol	NCEH1
Name	neutral cholesterol ester hydrolase 1
Location	3q26.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1363, NCEH
Ensembl gene	ENSG00000144959
Ensembl biotype	protein_coding
OMIM	613234
Entrez	57552

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000421723, ENST00000424772, ENST00000470419, ENST00000475381, ENST00000538775, ENST00000543711, ENST00000894447, ENST00000956792

RefSeq mRNA: 4 — MANE Select: NM_020792 NM_001146276, NM_001146277, NM_001146278, NM_020792

CCDS: CCDS33893, CCDS54681

Canonical transcript exons

ENST00000475381 — 5 exons

Exon	Start	End
ENSE00000968092	172647886	172648114
ENSE00001869349	172630249	172634092
ENSE00003599541	172635916	172636087
ENSE00003680398	172645623	172645692
ENSE00003846332	172710847	172711067

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 91.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.1846 / max 245.5786, expressed in 1737 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45642	20.2187	1725
45643	1.2750	734
45641	0.6909	441

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	91.72	gold quality
secondary oocyte	CL:0000655	90.67	gold quality
islet of Langerhans	UBERON:0000006	90.37	gold quality
adrenal tissue	UBERON:0018303	90.00	gold quality
prefrontal cortex	UBERON:0000451	89.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.15	gold quality
superior frontal gyrus	UBERON:0002661	88.89	gold quality
heart right ventricle	UBERON:0002080	88.77	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.66	gold quality
postcentral gyrus	UBERON:0002581	88.03	gold quality
parietal lobe	UBERON:0001872	87.39	gold quality
frontal cortex	UBERON:0001870	87.18	gold quality
primary visual cortex	UBERON:0002436	86.37	gold quality
caudate nucleus	UBERON:0001873	86.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.36	gold quality
neocortex	UBERON:0001950	86.14	gold quality
lower lobe of lung	UBERON:0008949	86.03	gold quality
putamen	UBERON:0001874	85.93	gold quality
heart left ventricle	UBERON:0002084	85.63	gold quality
cardiac ventricle	UBERON:0002082	85.61	gold quality
anterior cingulate cortex	UBERON:0009835	85.60	gold quality
occipital lobe	UBERON:0002021	85.15	gold quality
nucleus accumbens	UBERON:0001882	85.09	gold quality
cerebral cortex	UBERON:0000956	84.97	gold quality
oocyte	CL:0000023	84.83	gold quality
rectum	UBERON:0001052	84.23	gold quality
monocyte	CL:0000576	83.53	gold quality
right frontal lobe	UBERON:0002810	83.49	gold quality
mucosa of transverse colon	UBERON:0004991	83.33	gold quality
adrenal gland	UBERON:0002369	83.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-124858	yes	91.25
E-GEOD-81547	yes	22.95
E-ANND-3	yes	7.54
E-MTAB-9067	yes	3.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting NCEH1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520G-5P	99.99	66.76	658

Literature-anchored findings (GeneRIF, showing 13)

• KIAA1363, an uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and lysophosphatidic acid. (PMID:17052604)
• The KIAA1363, an uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and lysophosphatidic acid. (PMID:17052608)
• NCEH is responsible for a major part of nCEH activity in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis. (PMID:18782767)
• Ritonavir (at 100 mg once daily and 100 mg twice daily significantly down-regulated neutral cholesterol ester hydrolase 1 in 20 healthy individuals. (PMID:20353815)
• NCEH1 is expressed in human atheromatous lesions, where it plays a critical role in the hydrolysis of cholesterol ester in human macrophage foam cells, thereby contributing to the initial part of reverse cholesterol transport in human atherosclerosis. (PMID:20947831)
• Inhibition of AADACL1 activity with a variety of agents blocked platelet aggregation in response to multiple agonists; blocked activation of the small GTPase RAP1 and protein kinase C (PKC). (PMID:23993462)
• Pioglitazone increases ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRalpha-independent manner. (PMID:25280398)
• Together, the results define the kinetics of inhibition of KIAA1363 by active metabolites of agrochemicals and indicate that KIAA1363 is highly sensitive to inhibition by these compounds. (PMID:26617293)
• Psoriasis inflammation induced microRNA targets NCEH1 in underlying subcutaneous adipose tissue. (PMID:27015452)
• Authors discovered that the presence of cholesterol, LDLR-mediated cholesterol endocytosis, and cholesterol efflux are all essential to NCEH-1-mediated neuroprotection. In protecting from alpha-synuclein neurotoxicity, NCEH-1 also stimulates cholesterol-derived neurosteroid formation and lowers cellular reactive oxygen species in mitochondria. (PMID:28934392)
• Retinoic acid receptor-related orphan receptor alpha reduces lipid droplets by upregulating neutral cholesterol ester hydrolase 1 in macrophages. (PMID:32321446)
• NAD(P)-dependent steroid dehydrogenase-like protein and neutral cholesterol ester hydrolase 1 serve as novel markers for early detection of gastric cancer identified using quantitative proteomics. (PMID:33219617)
• KIAA1363 affects retinyl ester turnover in cultured murine and human hepatic stellate cells. (PMID:35101424)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	nceh1a	ENSDARG00000020427
danio_rerio	nceh1b.1	ENSDARG00000062087
danio_rerio	NCEH1	ENSDARG00000115549
mus_musculus	Nceh1	ENSMUSG00000027698
rattus_norvegicus	Nceh1	ENSRNOG00000013313
caenorhabditis_elegans		WBGENE00009186
caenorhabditis_elegans		WBGENE00011642
caenorhabditis_elegans		WBGENE00017515

Paralogs (5): AADAC (ENSG00000114771), AFMID (ENSG00000183077), AADACL3 (ENSG00000188984), AADACL2 (ENSG00000197953), AADACL4 (ENSG00000204518)

Protein

Protein identifiers

Neutral cholesterol ester hydrolase 1 — Q6PIU2 (reviewed: Q6PIU2)

Alternative names: Acetylalkylglycerol acetylhydrolase, Arylacetamide deacetylase-like 1

All UniProt accessions (4): Q6PIU2, A0A0A0MTJ9, F8WE33, H7C046

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes 2-acetyl monoalkylglycerol ether (1-O-alkyl-2-acetyl-sn-glycerol), the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor. May be responsible for the hydrolysis of cholesterol esters (such as cholesteryl (9Z-octadecenoate)) in macrophages. Also involved in organ detoxification by hydrolyzing exogenous organophosphorus compounds. May contribute to cancer pathogenesis by promoting tumor cell migration.

Subcellular location. Cell membrane. Microsome.

Tissue specificity. Expressed in monocyte-derived macrophages. Up-regulated in invasive melanoma and breast carcinoma cell lines.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the ‘GDXG’ lipolytic enzyme family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6PIU2-1	1	yes
Q6PIU2-2	2
Q6PIU2-3	3

RefSeq proteins (4): NP_001139748, NP_001139749, NP_001139750, NP_065843* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013094	AB_hydrolase_3	Domain
IPR017157	Arylacetamide_deacetylase	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033140	Lipase_GDXG_put_SER_AS	Active_site
IPR050300	GDXG_lipolytic_enzyme	Family

Pfam: PF07859

Enzyme classification (BRENDA):

• EC 3.1.1.13 — sterol esterase (BRENDA: 26 organisms, 244 substrates, 524 inhibitors, 68 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CHOLESTERYL OLEATE	0.002–1	13
4-NITROPHENYL BUTYRATE	0.061–0.73	7
CHOLESTERYL LINOLEATE	0.09–0.99	5
P-NITROPHENYL OCTANOATE	0.144–1.782	4
4-NITROPHENYL PALMITATE	0.33–1	3
CHOLESTERYL MYRISTATE	0.34–0.49	3
CHOLESTERYL PALMITATE	0.87–6.8	3
CHOLESTERYL STEARATE	1.1–7	3
P-NITROPHENYL HEXANOATE	0.0122–0.0384	3
4-NITROPHENYL LAURATE	0.53–0.63	2
4-NITROPHENYL MYRISTATE	0.77–0.8	2
LIPOYL 4-AMINOBENZOATE	0.011–0.024	2
P-NITROPHENYL BUTYRATE	0.052–0.073	2
P-NITROPHENYL CAPROATE	0.046–0.074	2
TRIOLEIN	0.05–0.98	2

Catalyzed reactions (Rhea), 4 shown:

• a 1-O-alkyl-2-acetyl-sn-glycerol + H2O = a 1-O-alkyl-sn-glycerol + acetate + H(+) (RHEA:11552)
• cholesteryl (9Z-octadecenoate) + H2O = cholesterol + (9Z)-octadecenoate + H(+) (RHEA:33875)
• a cholesterol ester + H2O = cholesterol + a fatty acid + H(+) (RHEA:36403)
• 1-O-hexadecyl-2-acetyl-sn-glycerol + H2O = 1-O-hexadecyl-sn-glycerol + acetate + H(+) (RHEA:38563)

UniProt features (22 total): sequence conflict 6, glycosylation site 3, sequence variant 3, active site 3, topological domain 2, splice variant 2, chain 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PIU2-F1	96.33	0.95

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 191; 348; 378

Glycosylation sites (3): 389, 270, 287

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8964038	LDL clearance
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8964043	Plasma lipoprotein clearance

MSigDB gene sets: 179 (showing top): chr3q26, GOBP_LOW_DENSITY_LIPOPROTEIN_PARTICLE_CLEARANCE, GOBP_PLASMA_LIPOPROTEIN_PARTICLE_CLEARANCE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_PLASMA_LIPOPROTEIN_PARTICLE_LEVELS, KUNINGER_IGF1_VS_PDGFB_TARGETS_DN, GOBP_LIPID_CATABOLIC_PROCESS, RGAGGAARY_PU1_Q6, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, SANA_TNF_SIGNALING_UP, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, SANSOM_APC_TARGETS_REQUIRE_MYC, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (5): xenobiotic metabolic process (GO:0006805), lipid catabolic process (GO:0016042), low-density lipoprotein particle clearance (GO:0034383), ether lipid metabolic process (GO:0046485), lipid metabolic process (GO:0006629)

GO Molecular Function (7): sterol ester esterase activity (GO:0004771), serine hydrolase activity (GO:0017171), phosphate ion binding (GO:0042301), acetylalkylglycerol acetylhydrolase activity (GO:0047378), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Plasma lipoprotein clearance	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
carboxylic ester hydrolase activity	2
metabolic process	1
cellular response to xenobiotic stimulus	1
catabolic process	1
plasma lipoprotein particle clearance	1
low-density lipoprotein particle disassembly	1
primary metabolic process	1
lipase activity	1
hydrolase activity	1
anion binding	1
molecular_function	1
catalytic activity	1
hydrolase activity, acting on ester bonds	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCEH1	MGLL	Q99685	960
NCEH1	CES1	P23141	884
NCEH1	SOAT1	P35610	665
NCEH1	ABHD6	Q9BV23	605
NCEH1	APOE	P02649	552
NCEH1	LIPA	P38571	541
NCEH1	ATP10D	Q9P241	524
NCEH1	FAAH	O00519	517
NCEH1	PAFAH2	Q99487	509
NCEH1	ABHD11	Q8NFV4	503
NCEH1	ABCA1	O95477	475
NCEH1	ABCG1	P45844	474
NCEH1	NPC1	O15118	458
NCEH1	PNPLA6	Q8IY17	442
NCEH1	RBBP9	O75884	433

IntAct

47 interactions, top by confidence:

A	B	Type	Score
STAM	HGS	psi-mi:“MI:0914”(association)	0.860
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
FAM177A1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
TMEM38A	DOK2	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
SGTB	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
	SCAMP3	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (151): NCEH1 (Affinity Capture-MS), NCEH1 (Affinity Capture-MS), NCEH1 (Affinity Capture-MS), NCEH1 (Affinity Capture-MS), NCEH1 (Affinity Capture-MS), NCEH1 (Affinity Capture-MS), UGT3A2 (Affinity Capture-MS), NRN1 (Affinity Capture-MS), LRRC3 (Affinity Capture-MS), TMEM231 (Affinity Capture-MS), ST3GAL6 (Affinity Capture-MS), CANT1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), NCEH1 (Affinity Capture-MS)

ESM2 similar proteins: A6H7A0, A6NI61, A6QQ59, B0BMW8, B0CM95, B0KWE9, B1MTH4, B2KI79, F1LTR1, O14494, O43688, O88956, P0CK96, P57791, P60588, P86229, Q0VBU9, Q13888, Q1JQE6, Q2HJ61, Q3ZCD7, Q4L208, Q4R8V4, Q5R589, Q5R8Y5, Q5RL79, Q5VZY2, Q5ZJ75, Q5ZJH8, Q64232, Q6PIU2, Q86YN1, Q8C811, Q8K593, Q8N6L1, Q8NFT2, Q8R4D1, Q8VDI9, Q91ZH7, Q9CY27

Diamond homologs: A0A0A1EQ07, A0A0H5BMX5, A0A2P1GIW2, A0A2P1GIW3, A0A2P1GIY1, A0A2P1GIY2, B5BLW5, I3PLR2, I4DST8, I4DST9, O06350, O53424, O64640, O64641, P15304, P16386, P22760, P24484, P37967, P54310, P9WK86, P9WK87, Q00675, Q05469, Q0CZH0, Q0P5B7, Q0ZPV7, Q5NUF3, Q5NUF4, Q5R8Y5, Q68J42, Q6PIU2, Q7D5F9, Q7M370, Q940G6, Q9EX73, Q9FG13, Q9FX92, Q9FX93, Q9FX94

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

56 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1225 predictions. Top by Δscore:

Variant	Effect	Δscore
3:172635911:GTTA:G	donor_loss	1.0000
3:172635912:TTA:T	donor_loss	1.0000
3:172635914:AC:A	donor_loss	1.0000
3:172635915:C:A	donor_loss	1.0000
3:172645614:ATTAC:A	donor_loss	1.0000
3:172645615:TTAC:T	donor_loss	1.0000
3:172645616:TAC:T	donor_loss	1.0000
3:172645617:AC:A	donor_loss	1.0000
3:172645618:C:CG	donor_loss	1.0000
3:172645619:T:TA	donor_loss	1.0000
3:172645620:TA:T	donor_loss	1.0000
3:172645621:A:AC	donor_gain	1.0000
3:172645621:AC:A	donor_loss	1.0000
3:172645621:ACT:A	donor_gain	1.0000
3:172645622:C:CA	donor_gain	1.0000
3:172645622:CT:C	donor_gain	1.0000
3:172645622:CTC:C	donor_gain	1.0000
3:172645622:CTCA:C	donor_gain	1.0000
3:172645622:CTCAA:C	donor_gain	1.0000
3:172645690:TTT:T	acceptor_gain	1.0000
3:172645691:TT:T	acceptor_gain	1.0000
3:172645693:C:CC	acceptor_gain	1.0000
3:172645693:C:G	acceptor_loss	1.0000
3:172647884:A:AC	donor_gain	1.0000
3:172647885:C:CC	donor_gain	1.0000
3:172647908:T:TA	donor_gain	1.0000
3:172648045:C:CT	acceptor_gain	1.0000
3:172648046:A:T	acceptor_gain	1.0000
3:172710846:CCA:C	donor_gain	1.0000
3:172634093:C:CC	acceptor_gain	0.9900

AlphaMissense

2661 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:172647904:A:G	W117R	0.999
3:172647904:A:T	W117R	0.999
3:172633570:G:C	H378D	0.998
3:172633659:T:A	D348V	0.998
3:172633659:T:G	D348A	0.998
3:172633660:C:G	D348H	0.998
3:172635950:G:T	A192D	0.998
3:172635956:T:A	D190V	0.998
3:172647912:C:A	G114V	0.998
3:172647912:C:T	G114E	0.998
3:172633566:C:T	G379E	0.997
3:172633568:G:C	H378Q	0.997
3:172633568:G:T	H378Q	0.997
3:172633570:G:T	H378N	0.997
3:172633648:C:G	D352H	0.997
3:172635953:C:A	S191I	0.997
3:172635957:C:G	D190H	0.997
3:172635959:C:A	G189V	0.997
3:172635959:C:T	G189D	0.997
3:172647902:C:A	W117C	0.997
3:172647902:C:G	W117C	0.997
3:172710863:C:G	R41P	0.997
3:172633653:A:T	L350H	0.996
3:172633659:T:C	D348G	0.996
3:172633660:C:A	D348Y	0.996
3:172635947:C:A	G193V	0.996
3:172635947:C:T	G193D	0.996
3:172635952:A:C	S191R	0.996
3:172635952:A:T	S191R	0.996
3:172635954:T:G	S191R	0.996

dbSNP variants (sampled 300 via entrez): RS1000003990 (3:172648210 C>T), RS1000025269 (3:172669207 G>T), RS1000047592 (3:172691997 T>A,C,G), RS1000127408 (3:172677772 C>T), RS1000203399 (3:172668968 G>T), RS1000204869 (3:172648439 C>A,T), RS1000399566 (3:172636449 T>C), RS1000429556 (3:172642488 C>A), RS1000450616 (3:172636022 T>C), RS1000452413 (3:172674480 A>C,T), RS1000455321 (3:172680695 A>G), RS1000456027 (3:172647900 G>A), RS1000500138 (3:172686537 T>C), RS1000559338 (3:172654083 T>C), RS1000585649 (3:172680660 G>A)

Disease associations

OMIM: gene MIM:613234 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_523	Obesity-related traits	8.000000e-06
GCST004490_4	Cerebrospinal fluid t-tau:AB1-42 ratio	3.000000e-08
GCST007565_2	Morning person	3.000000e-15
GCST007576_35	Chronotype	3.000000e-15
GCST90011898_157	Alanine aminotransferase levels	5.000000e-16
GCST90011899_195	Aspartate aminotransferase levels	2.000000e-20

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0008328	chronotype measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5048 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

32 potent at pChembl≥5 of 59 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	CHEMBL2071652
7.10	IC50	80	nM	CHEMBL2071655
7.00	IC50	100	nM	CHEMBL2069333
6.89	IC50	130	nM	CHEMBL2071651
6.82	IC50	150	nM	CHEMBL2069333
6.82	IC50	150	nM	CHEMBL2071654
6.82	IC50	150	nM	CHEMBL2071653
6.82	IC50	150	nM	CHEMBL2071650
6.51	IC50	310	nM	CHEMBL2071649
6.48	IC50	330	nM	CHEMBL2071656
6.48	IC50	330	nM	CHEMBL2071641
6.15	IC50	710	nM	CHEMBL2071659
6.05	IC50	890	nM	CHEMBL2071640
6.04	IC50	920	nM	CHEMBL2071646
6.04	IC50	920	nM	CHEMBL2071629
5.96	IC50	1100	nM	CHEMBL2069332
5.96	IC50	1100	nM	CHEMBL1481956
5.92	IC50	1200	nM	CHEMBL2071626
5.89	IC50	1300	nM	CHEMBL2071647
5.82	IC50	1500	nM	CHEMBL2071658
5.82	IC50	1500	nM	CHEMBL2071645
5.77	IC50	1700	nM	CHEMBL2071626
5.77	IC50	1700	nM	CHEMBL2071643
5.70	IC50	2000	nM	CHEMBL2071656
5.66	IC50	2200	nM	CHEMBL2071657
5.47	IC50	3400	nM	CHEMBL2071634
5.41	IC50	3900	nM	CHEMBL2069331
5.27	IC50	5400	nM	CHEMBL2069333
5.17	IC50	6800	nM	CHEMBL2071633
5.12	IC50	7500	nM	CHEMBL2071635
5.00	IC50	1e+04	nM	CHEMBL461544
5.00	IC50	1e+04	nM	CHEMBL158897

PubChem BioAssay actives

32 with measured affinity, of 158 total; 28 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1,6-dibromonaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.0500	uM
(6-bromo-1-chloronaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.0800	uM
(2-fluorophenyl) N-[2-[[(1R,2S)-2-(butoxymethyl)cyclohexyl]methoxy]ethyl]carbamate	678174: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 4 hrs measured after 1 hr	ic50	0.1000	uM
(1-bromo-6-propylnaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.1300	uM
(1-chloro-6-propylnaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.1500	uM
(1-chloro-6-cyanonaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.1500	uM
(1-bromo-6-cyanonaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.1500	uM
[1-bromo-6-(4-phenylpiperazine-1-carbonyl)naphthalen-2-yl] N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.3100	uM
(1-bromonaphthalen-2-yl) azetidine-1-carboxylate	678174: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 4 hrs measured after 1 hr	ic50	0.3300	uM
(1-iodonaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.3300	uM
(1-bromonaphthalen-2-yl) N-benzylcarbamate	678174: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 4 hrs measured after 1 hr	ic50	0.7100	uM
(1-nitronaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.8900	uM
[1-bromo-6-(cycloheptylcarbamoyl)naphthalen-2-yl] N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.9200	uM
(6-bromonaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	0.9200	uM
(1-chloronaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	1.1000	uM
(1-bromonaphthalen-2-yl) piperidine-1-carboxylate	678174: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 4 hrs measured after 1 hr	ic50	1.1000	uM
(1-bromonaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	1.2000	uM
[1-bromo-6-(phenylcarbamoyl)naphthalen-2-yl] N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	1.3000	uM
(1-bromonaphthalen-2-yl) N-propan-2-ylcarbamate	678174: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 4 hrs measured after 1 hr	ic50	1.5000	uM
[1-bromo-6-(cyclopentylcarbamoyl)naphthalen-2-yl] N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	1.5000	uM
[1-bromo-6-(heptylcarbamoyl)naphthalen-2-yl] N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	1.7000	uM
(1-bromonaphthalen-2-yl) N-butylcarbamate	678174: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 4 hrs measured after 1 hr	ic50	2.2000	uM
(1-propylnaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	3.4000	uM
methyl 2-(dimethylcarbamoyloxy)naphthalene-1-carboxylate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	3.9000	uM
(1-ethylnaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	6.8000	uM
(1-butylnaphthalen-2-yl) N,N-dimethylcarbamate	678173: Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	ic50	7.5000	uM
7-phenyl-1-[4-(trifluoromethyl)-1,3-oxazol-2-yl]heptan-1-one	409625: Inhibition of KIAA1363	ic50	10.0000	uM
(cyclohexylideneamino) N-[6-[(cyclohexylideneamino)oxycarbonylamino]hexyl]carbamate	409656: Inhibition of recombinant KIAA1363 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe	ic50	10.0000	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
bisphenol A	increases methylation, decreases expression, decreases methylation, affects cotreatment	4
Benzo(a)pyrene	increases expression, increases mutagenesis, affects methylation, decreases methylation	3
Air Pollutants	increases expression, decreases expression, increases abundance	2
Nickel	increases expression	2
Smoke	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
incobotulinumtoxinA	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Dasatinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2072018	Binding	Inhibition of human KIAA1363 expressed in 293T/17 cells using 2-thioacetyl MAGE as substrate preincubated for 20 mins measured after 1 hr	Synthesis and structure-activity relationship of (1-halo-2-naphthyl) carbamate-based inhibitors of KIAA1363 (NCEH1/AADACL1). — Bioorg Med Chem Lett

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.