NAAA

Summary

NAAA (N-acylethanolamine acid amidase, HGNC:736) is a protein-coding gene on chromosome 4q21.1, encoding N-acylethanolamine-hydrolyzing acid amidase (Q02083). Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine > N-arachidonoylethanolamine > N-oleoylethanolamine.

Enables DNA-binding transcription factor binding activity and hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides. Involved in several processes, including N-acylethanolamine metabolic process; N-acylphosphatidylethanolamine metabolic process; and sphingosine metabolic process. Located in lysosome and membrane.

Source: NCBI Gene 27163 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:736
Approved symbol	NAAA
Name	N-acylethanolamine acid amidase
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138744
Ensembl biotype	protein_coding
OMIM	607469
Entrez	27163

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000286733, ENST00000503636, ENST00000505594, ENST00000507187, ENST00000507940, ENST00000507956, ENST00000511606, ENST00000513045, ENST00000602782, ENST00000718295, ENST00000967490, ENST00000967491, ENST00000967492

RefSeq mRNA: 3 — MANE Select: NM_014435 NM_001042402, NM_001363719, NM_014435

CCDS: CCDS43239, CCDS87233

Canonical transcript exons

ENST00000286733 — 11 exons

Exon	Start	End
ENSE00001025184	75925735	75925811
ENSE00001139251	75936109	75936235
ENSE00001193334	75920951	75921123
ENSE00001291278	75918761	75918789
ENSE00001411606	75931214	75931304
ENSE00001538638	75913660	75914338
ENSE00001805590	75940001	75940165
ENSE00003504208	75920738	75920800
ENSE00003528717	75919909	75919975
ENSE00003620892	75914868	75914985
ENSE00004034663	75940744	75941013

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.5065 / max 694.8691, expressed in 1652 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52610	19.9444	1639
52609	0.7967	380
52608	0.7654	394

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.09	gold quality
leukocyte	CL:0000738	98.02	gold quality
mononuclear cell	CL:0000842	98.01	gold quality
granulocyte	CL:0000094	97.66	gold quality
rectum	UBERON:0001052	96.97	gold quality
mucosa of transverse colon	UBERON:0004991	96.26	gold quality
spleen	UBERON:0002106	94.25	gold quality
colonic mucosa	UBERON:0000317	94.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.45	gold quality
transverse colon	UBERON:0001157	93.30	gold quality
blood	UBERON:0000178	92.87	gold quality
lymph node	UBERON:0000029	92.54	gold quality
minor salivary gland	UBERON:0001830	92.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.85	gold quality
prostate gland	UBERON:0002367	91.52	gold quality
vermiform appendix	UBERON:0001154	91.42	gold quality
saliva-secreting gland	UBERON:0001044	91.41	gold quality
right lobe of liver	UBERON:0001114	91.38	gold quality
right coronary artery	UBERON:0001625	91.23	gold quality
ileal mucosa	UBERON:0000331	91.03	gold quality
mouth mucosa	UBERON:0003729	90.72	gold quality
small intestine	UBERON:0002108	90.68	gold quality
caecum	UBERON:0001153	90.42	gold quality
descending thoracic aorta	UBERON:0002345	90.27	gold quality
thoracic aorta	UBERON:0001515	90.23	gold quality
ascending aorta	UBERON:0001496	90.13	gold quality
intestine	UBERON:0000160	90.09	gold quality
large intestine	UBERON:0000059	90.03	gold quality
colon	UBERON:0001155	89.84	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	3059.11
E-HCAD-1	yes	23.31
E-MTAB-6701	yes	21.88
E-MTAB-6678	yes	8.60
E-MTAB-10042	yes	8.40
E-MTAB-9801	yes	7.64
E-GEOD-106540	no	626.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

56 targeting NAAA, 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-4262	100.00	73.26	3931
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-6808-5P	99.31	66.23	2150

Literature-anchored findings (GeneRIF, showing 9)

• The level and activity of acid ceramidase in Alzheimer disease (AD) brain may play a role in controlling neuronal apoptosis and may mediate signalling pathways involved in the molecular mechanism of AD. (PMID:15610181)
• Asn-37, Asn-107, Asn-309, and Asn-333 are actual N-glycosylation sites. The glycosylation appeared to play an important role in stabilizing the enzyme protein. (PMID:17980170)
• we describe the overexpression and processing of recombinant human acid ceramidase in insect cells, its purification and characterization (PMID:18020949)
• These results showed that both N-acylethanolamine-hydrolysing acid amidase and fatty acid amide hydrolase are functionally active in human prostate cancer cells. (PMID:18806270)
• MALDI-TOF MS analysis of the human NAAA zymogen (47.7 kDa) treated with peptide-N-glycosidase F (PNGase F) identified 4 glycosylation sites, and acid cleavage of the zymogen into alpha- and beta-subunits (14.6 and 33.3 kDa) activated the enzyme. (PMID:22040171)
• The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive prostate cancer (PMID:24741114)
• Variants a1 and a2 encoded the same full-length NAAA protein. (PMID:27693242)
• The rs2276886 SNP was found to be significantly associated with Hashimoto’s Thyroiditis susceptibility. However, our findings suggest that this SNP which maps to the chromosomal region 4q21.1 likely effects the NAAA gene (as opposed to the CXCL9 gene), but still contributes to the susceptibility to Hashimoto’s Thyroiditis in Han Chinese populations. (PMID:31750736)
• Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer. (PMID:35069601)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Naaa	ENSMUSG00000029413
rattus_norvegicus	Naaa	ENSRNOG00000002273
caenorhabditis_elegans		WBGENE00021917

Paralogs (1): ASAH1 (ENSG00000104763)

Protein

Protein identifiers

N-acylethanolamine-hydrolyzing acid amidase — Q02083 (reviewed: Q02083)

Alternative names: Acid ceramidase-like protein, Acylsphingosine deacylase NAAA, N-acylsphingosine amidohydrolase-like

All UniProt accessions (5): Q02083, B4DVL2, D6R9S9, H0Y988, R4GNC0

UniProt curated annotations — full annotation on UniProt →

Function. Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine > N-arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N-lauroylsphingosine and N-palmitoylsphingosine.

Subunit / interactions. Heterodimer of an alpha and a beta subunit, produced by autocatalytic cleavage.

Subcellular location. Lysosome. Membrane.

Tissue specificity. Expressed in numerous tissues, with highest levels in liver and kidney, followed by pancreas.

Post-translational modifications. N-glycosylated. Tunicamycin treatment causes a reduction in specific activity against N-palmitoylethanolamine. A disulfide bond is seen in the crystal structure of the human protein, but the Cys residues are not conserved in rodents. Autoproteolytic cleavage at pH 4.5 gives rise to the alpha and beta subunit. Cleavage gives rise to a conformation change that activates the enzyme. The same catalytic Cys residue mediates the autoproteolytic cleavage and subsequent hydrolysis of lipid substrates.

Activity regulation. Stimulated by DTT and Nonidet P-40.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the acid ceramidase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q02083-1	1	yes
Q02083-2	2
Q02083-3	3

RefSeq proteins (3): NP_001035861, NP_001350648, NP_055250* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016699	Acid_ceramidase-like	Family
IPR029130	Acid_ceramidase_N	Domain
IPR029132	CBAH/NAAA_C	Domain

Pfam: PF02275, PF15508

Enzyme classification (BRENDA):

• EC 3.5.1.4 — amidase (BRENDA: 67 organisms, 400 substrates, 635 inhibitors, 203 Km, 135 kcat entries)
• EC 3.5.1.60 — N-(long-chain-acyl)ethanolamine deacylase (BRENDA: 6 organisms, 58 substrates, 415 inhibitors, 24 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ACETAMIDE	0.27–100	25
PROPIONAMIDE	0.0001–88	18
BENZAMIDE	0.0007–7.25	17
ACRYLAMIDE	1.2–93	16
ISOBUTYRAMIDE	0.0001–7	10
BUTYRAMIDE	0.1–14	7
NICOTINAMIDE	0.3–135.6	6
HEXANAMIDE	0.3–11.08	5
2-TOLUAMIDE	0.1–0.3	4
CYCLOMALTOHEXAOSE	0.2–0.3	4
P-NITROACETANILIDE	0.5–1.98	4
3-PHENYLPROPIONAMIDE	2.5–4	3
4-HYDROXYBENZAMIDE	0.1–1.5	3
ARACHIDONOYL-ETHANOLAMINE	0.0033–0.0041	3
INDOL-3-ACETAMIDE	0.8–1.225	3

Catalyzed reactions (Rhea), 7 shown:

• an N-(long-chain fatty acyl)ethanolamine + H2O = a long-chain fatty acid + ethanolamine (RHEA:17505)
• an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid (RHEA:20856)
• N-hexadecanoylsphing-4-enine + H2O = sphing-4-enine + hexadecanoate (RHEA:38891)
• N-dodecanoylsphing-4-enine + H2O = dodecanoate + sphing-4-enine (RHEA:41291)
• N-hexadecanoylethanolamine + H2O = ethanolamine + hexadecanoate (RHEA:45064)
• N-tetradecanoylethanolamine + H2O = tetradecanoate + ethanolamine (RHEA:45452)
• N-dodecanoylethanolamine + H2O = dodecanoate + ethanolamine (RHEA:45456)

UniProt features (63 total): helix 15, strand 14, mutagenesis site 10, glycosylation site 4, chain 3, splice variant 3, sequence variant 3, sequence conflict 3, turn 3, site 2, signal peptide 1, disulfide bond 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6DXW	X-RAY DIFFRACTION	2.3
6DXX	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02083-F1	92.67	0.89

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): 126 (nucleophile); 142 (important for enzyme activity); 287 (important for enzyme activity)

Disulfide bonds (1): 103–113

Glycosylation sites (4): 333, 37, 107, 309

Mutagenesis-validated functional residues (10):

Position	Phenotype
116	decreased autoproteolytic cleavage and strongly reduced enzyme activity with liposome-bound substrate. loss of enzyme ac
126	loss of autoproteolytic cleavage and loss of enzyme activity.
142	loss of autoproteolytic cleavage and loss of enzyme activity.
145	loss of autoproteolytic cleavage and loss of enzyme activity.
152	strongly reduced enzyme activity both with liposome-bound and triton-solubilized substrate.
195	abolishes decrease of enzyme activity at ph 6 and ph 7.
287	loss of autoproteolytic cleavage and loss of enzyme activity.
309	loss of one glycosylation site.
333	loss of one glycosylation site.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System

MSigDB gene sets: 217 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, AATGGAG_MIR136, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_SPHINGOID_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_DIOL_METABOLIC_PROCESS

GO Biological Process (6): fatty acid metabolic process (GO:0006631), sphingosine metabolic process (GO:0006670), lipid catabolic process (GO:0016042), N-acylethanolamine metabolic process (GO:0070291), N-acylphosphatidylethanolamine metabolic process (GO:0070292), lipid metabolic process (GO:0006629)

GO Molecular Function (6): hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810), N-acylsphingosine amidohydrolase activity (GO:0017040), fatty acid amide hydrolase activity (GO:0017064), N-(long-chain-acyl)ethanolamine deacylase activity (GO:0047412), DNA-binding transcription factor binding (GO:0140297), hydrolase activity (GO:0016787)

GO Cellular Component (5): cytoplasm (GO:0005737), lysosome (GO:0005764), membrane (GO:0016020), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	3
lipid metabolic process	2
cellular anatomical structure	2
monocarboxylic acid metabolic process	1
diol metabolic process	1
sphingoid metabolic process	1
catabolic process	1
primary alcohol metabolic process	1
phosphatidylethanolamine metabolic process	1
primary metabolic process	1
hydrolase activity	1
transcription factor binding	1
catalytic activity	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

1826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAAA	FAAH	O00519	848
NAAA	FIG4	Q92562	839
NAAA	NAPEPLD	Q6IQ20	816
NAAA	LAMP2	P13473	772
NAAA	VAC14	Q08AM6	761
NAAA	FAAH2	Q6GMR7	749
NAAA	MGLL	Q99685	711
NAAA	PPARA	Q07869	702
NAAA	GPR55	Q9Y2T6	660
NAAA	ABHD4	Q8TB40	658
NAAA	DAGLB	Q8NCG7	642
NAAA	DAGLA	Q9Y4D2	637
NAAA	ABHD6	Q9BV23	633
NAAA	ABHD12	Q8N2K0	615
NAAA	GDE1	Q9NZC3	614

IntAct

35 interactions, top by confidence:

A	B	Type	Score
PLAUR	PLAU	psi-mi:“MI:0914”(association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530
	HLA-C	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
RD3	LRBA	psi-mi:“MI:0914”(association)	0.350
PCDHB3	ESYT2	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
IDS	RTCA	psi-mi:“MI:0914”(association)	0.350
C1QB	MANBA	psi-mi:“MI:0914”(association)	0.350
ALPP	MAN2B1	psi-mi:“MI:0914”(association)	0.350
LYZL1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
FIBIN	MAN2B1	psi-mi:“MI:0914”(association)	0.350
LIPG	TOR1B	psi-mi:“MI:0914”(association)	0.350
KLK15	APAF1	psi-mi:“MI:0914”(association)	0.350
ARSA	CLGN	psi-mi:“MI:0914”(association)	0.350
PSCA	GPAA1	psi-mi:“MI:0914”(association)	0.350
NAGA	ACSL4	psi-mi:“MI:0914”(association)	0.350
CRISP2	LRP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (285): NAAA (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TCTN2 (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), ENTPD6 (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), MANEAL (Affinity Capture-MS), SLC38A10 (Affinity Capture-MS), ARSK (Affinity Capture-MS), GALNS (Affinity Capture-MS), OAF (Affinity Capture-MS), EXT1 (Affinity Capture-MS), SYVN1 (Affinity Capture-MS), OS9 (Affinity Capture-MS), TTC17 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P6JG37, A0A383ZFX3, A5A6P2, A6MFL0, A8QL51, A8QL52, F8J2D3, F8S101, G1T7U7, G8XQX1, H0VCJ6, J7H670, O45686, O62146, P0C2D5, P16278, P23780, P81382, P86810, Q02083, Q06K61, Q09551, Q13510, Q17QB3, Q19426, Q2VQV9, Q4JHE2, Q54CS6, Q55BZ5, Q5KTC7, Q5MIX2, Q5R7P4, Q5U2V4, Q5UR76, Q60HH4, Q6L6S1, Q6P4A8, Q6P7S1, Q6STF1, Q6WP39

Diamond homologs: A0A0P6JG37, A0A383ZFX3, A5A6P2, G1T7U7, H0VCJ6, O45686, Q02083, Q09551, Q13510, Q17QB3, Q5KTC7, Q60HH4, Q6P7S1, Q9D7V9, Q9GUI1, Q9WV54

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	10	6.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1618 predictions. Top by Δscore:

Variant	Effect	Δscore
4:75919904:GTTAC:G	donor_loss	1.0000
4:75919905:TTACC:T	donor_loss	1.0000
4:75919906:TA:T	donor_loss	1.0000
4:75919907:A:C	donor_loss	1.0000
4:75919908:C:G	donor_loss	1.0000
4:75919972:TGTT:T	acceptor_gain	1.0000
4:75919974:TT:T	acceptor_gain	1.0000
4:75919974:TTC:T	acceptor_loss	1.0000
4:75919975:TC:T	acceptor_loss	1.0000
4:75919976:C:CC	acceptor_gain	1.0000
4:75919976:CT:C	acceptor_loss	1.0000
4:75919977:T:C	acceptor_loss	1.0000
4:75920735:TACC:T	donor_loss	1.0000
4:75920736:ACC:A	donor_loss	1.0000
4:75920739:T:TA	donor_gain	1.0000
4:75920949:A:AC	donor_gain	1.0000
4:75920949:ACGCT:A	donor_gain	1.0000
4:75920950:C:CC	donor_gain	1.0000
4:75920950:CG:C	donor_gain	1.0000
4:75920950:CGCTC:C	donor_gain	1.0000
4:75939994:CACT:C	donor_loss	1.0000
4:75939995:ACTC:A	donor_loss	1.0000
4:75939997:TCAC:T	donor_loss	1.0000
4:75939998:CACAC:C	donor_loss	1.0000
4:75939999:A:AC	donor_gain	1.0000
4:75940000:C:CC	donor_gain	1.0000
4:75940000:CA:C	donor_gain	1.0000
4:75940000:CACG:C	donor_gain	1.0000
4:75940000:CACGG:C	donor_gain	1.0000
4:75940740:TCA:T	donor_loss	1.0000

AlphaMissense

2319 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:75925750:G:C	S217R	0.981
4:75925750:G:T	S217R	0.981
4:75925752:T:G	S217R	0.981
4:75940808:A:G	W48R	0.981
4:75940808:A:T	W48R	0.981
4:75936124:G:C	F161L	0.977
4:75936124:G:T	F161L	0.977
4:75936126:A:G	F161L	0.977
4:75920794:G:C	F282L	0.974
4:75920794:G:T	F282L	0.974
4:75920796:A:G	F282L	0.974
4:75936182:C:G	R142P	0.973
4:75936125:A:G	F161S	0.969
4:75931236:A:C	F189L	0.968
4:75931236:A:T	F189L	0.968
4:75931238:A:G	F189L	0.968
4:75940021:G:C	N117K	0.966
4:75940021:G:T	N117K	0.966
4:75936223:A:C	S128R	0.965
4:75936223:A:T	S128R	0.965
4:75936225:T:G	S128R	0.965
4:75931252:T:G	Q184P	0.964
4:75931255:C:T	G183D	0.959
4:75940806:C:A	W48C	0.959
4:75940806:C:G	W48C	0.959
4:75931296:G:C	F169L	0.958
4:75931296:G:T	F169L	0.958
4:75931298:A:G	F169L	0.958
4:75925749:A:G	W218R	0.957
4:75925749:A:T	W218R	0.957

dbSNP variants (sampled 300 via entrez): RS1000074165 (4:75942970 G>T), RS1000122753 (4:75930796 C>A,T), RS1000208430 (4:75912977 A>C), RS1000382616 (4:75912861 T>C), RS1000461105 (4:75929350 T>C), RS1000595545 (4:75914670 C>T), RS1000722920 (4:75923400 G>A), RS1000753006 (4:75924676 G>A), RS1000821780 (4:75917424 A>G), RS1000908585 (4:75941341 C>T), RS1000987496 (4:75923182 G>A), RS1001098160 (4:75929016 T>A), RS1001118217 (4:75935913 A>G), RS1001143397 (4:75931504 A>T), RS1001268465 (4:75931995 C>T)

Disease associations

OMIM: gene MIM:607469 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005173_82	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	8.000000e-06
GCST006585_1178	Blood protein levels	4.000000e-159
GCST007009_3	Hippocampal volume	7.000000e-07
GCST008478_18	Neurological blood protein biomarker levels	3.000000e-19

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0005035	hippocampal volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4349 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 19,856 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL41286	DIACEREIN	3	5,090
CHEMBL2387742	CANNABIDIVARIN	2	4,963
CHEMBL498672	CANNABIDIOLIC ACID	2	9,803

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — N-Acylethanolamine turnover

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
F215	Inhibition	8.05	pIC50
ARN726	Irreversible inhibition	7.57	pIC50
ARN19702	Inhibition	6.64	pIC50
S-OOPP	Inhibition	6.4	pIC50
CCP	Inhibition	5.3	pIC50

Binding affinities (BindingDB)

115 measured of 188 human assays (188 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-phenylpentyl N-[(2R,3R)-2-ethyl-4-oxooxetan-3-yl]carbamate	IC50	4 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
[(2S)-nonan-2-yl] N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	5 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
5-cyclohexylpentyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	5 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
(4-phenylphenyl)methyl N-[(2R,3R)-2-ethyl-4-oxooxetan-3-yl]carbamate	IC50	6 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
(4-phenylphenyl)methyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	7 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
4-cyclohexylbutyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	8 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
5-phenylpentyl N-[(2S,3R)-2-ethyl-4-oxooxetan-3-yl]carbamate	IC50	9 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
1-(4-phenylphenyl)ethyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	10 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
(2-methyl-6-phenylhexan-2-yl) N-[(3R,4R)-2-oxo-4-propan-2-yloxetan-3-yl]carbamate	IC50	12 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
6-phenylhexan-2-yl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	14 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
5-phenylpentyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	14 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
(4-phenylphenyl)methyl N-[(2S,3R)-2-ethyl-4-oxooxetan-3-yl]carbamate	IC50	15 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
3-phenylmethoxypropyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	IC50	18 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
5-phenylpentyl N-[(3R,4R)-2-oxo-4-propan-2-yloxetan-3-yl]carbamate	IC50	19 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
(4-phenylphenyl)methyl N-[(3R,4R)-2-oxo-4-propan-2-yloxetan-3-yl]carbamate	IC50	23 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
(4-phenylphenyl)methyl N-[(3R,4S)-2-oxo-4-propan-2-yloxetan-3-yl]carbamate	IC50	37 nM	US-9353075: Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
10-isothiocyanatodecylbenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-(10-isothiocyanatodecyl)pyridine	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
4-(10-isothiocyanatodecyl)pyridine	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-(10-isothiocyanatodecyl)pyrimidine	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
11-isothiocyanatoundecylbenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
9-isothiocyanatononylbenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-[2-(2-isothiocyanatoethoxy)ethoxy]ethoxymethylbenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
1-(3-isothiocyanatopropoxymethyl)-3-phenylbenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
1-(3-isothiocyanatopropoxymethyl)-4-phenylbenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
1-(3-isothiocyanatopropoxymethyl)-4-phenoxybenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
4-benzyl-1-(5-isothiocyanatopentyl)piperidine	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
1-[(3-isothiocyanatocyclobutyl)oxymethyl]-4-(4-methylphenyl)benzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-fluoro-4-[3-fluoro-4-[(3-isothiocyanatocyclobutyl)oxymethyl]phenyl]-1-methoxybenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
1-[(3-isothiocyanatocyclobutyl)oxymethyl]-4-(3-methoxyphenyl)benzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
1-ethoxy-2-fluoro-4-[3-fluoro-4-[(3-isothiocyanatocyclobutyl)oxymethyl]phenyl]benzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
6-[3-fluoro-4-[(3-isothiocyanatocyclobutyl)oxymethyl]phenyl]-2,3-dihydro-1,4-benzodioxine	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
5-[3-fluoro-4-[(3-isothiocyanatocyclobutyl)oxymethyl]phenyl]-1,3-benzodioxole	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
4-(3,4-dimethoxyphenyl)-2-fluoro-1-[(3-isothiocyanatocyclobutyl)oxymethyl]benzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
5-(3-fluoro-4-methoxyphenyl)-2-[(3-isothiocyanatocyclobutyl)oxymethyl]pyridine	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-fluoro-1-[(3-isothiocyanatocyclobutyl)oxymethyl]-4-[3-(trifluoromethyl)phenyl]benzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-fluoro-1-[(3-isothiocyanatocyclobutyl)oxymethyl]-4-(3-phenylmethoxyphenyl)benzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
2-fluoro-4-[4-(3-isothiocyanatocyclobutyl)oxyphenyl]-1-methoxybenzene	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-(4-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[(4-phenylphenyl)methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-(2,4-dimethoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[(3-phenylphenyl)methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-(3-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-(2,5-dimethoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-(2,3-dimethoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-[3-(trifluoromethyl)phenyl]phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-[3,5-bis(trifluoromethyl)phenyl]phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[(4-pyridin-3-ylphenyl)methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
3-[[4-(6-methoxy-3-pyridinyl)phenyl]methoxy]azetidine-1-carbonitrile	IC50	55 nM	US-9963444: N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof

ChEMBL bioactivities

479 potent at pChembl≥5 of 517 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.46	IC50	0.35	nM	CHEMBL4633233
9.34	IC50	0.46	nM	CHEMBL4640552
9.33	IC50	0.47	nM	CHEMBL4642793
9.17	IC50	0.68	nM	CHEMBL4635208
9.07	IC50	0.85	nM	CHEMBL4640519
9.06	IC50	0.88	nM	CHEMBL4644090
9.05	IC50	0.89	nM	CHEMBL4633213
9.05	IC50	0.9	nM	CHEMBL4633213
9.03	IC50	0.94	nM	CHEMBL4649536
8.99	IC50	1.03	nM	CHEMBL4637701
8.96	IC50	1.1	nM	CHEMBL4646880
8.85	IC50	1.4	nM	CHEMBL4632623
8.80	IC50	1.6	nM	CHEMBL4645560
8.80	IC50	1.58	nM	CHEMBL4635238
8.80	IC50	1.6	nM	CHEMBL4646586
8.74	IC50	1.8	nM	CHEMBL4641417
8.64	IC50	2.3	nM	CHEMBL4872294
8.60	IC50	2.5	nM	CHEMBL4643427
8.55	IC50	2.8	nM	CHEMBL4637755
8.55	IC50	2.8	nM	CHEMBL4642907
8.55	IC50	2.8	nM	CHEMBL4636322
8.49	IC50	3.2	nM	CHEMBL4643588
8.49	IC50	3.2	nM	CHEMBL4848238
8.47	IC50	3.4	nM	CHEMBL4645262
8.40	IC50	4	nM	CHEMBL4111175
8.35	IC50	4.5	nM	CHEMBL4863412
8.34	IC50	4.6	nM	CHEMBL4638402
8.30	IC50	5	nM	CHEMBL2419811
8.30	IC50	5	nM	CHEMBL2419830
8.24	IC50	5.8	nM	CHEMBL4638779
8.24	IC50	5.7	nM	CHEMBL4639554
8.22	IC50	6	nM	CHEMBL4108761
8.22	IC50	6	nM	CHEMBL4101070
8.22	IC50	6	nM	CHEMBL4093333
8.22	IC50	6	nM	CHEMBL4647961
8.22	IC50	6	nM	CHEMBL3770726
8.21	IC50	6.1	nM	CHEMBL4643074
8.20	IC50	6.3	nM	CHEMBL4868148
8.19	IC50	6.5	nM	CHEMBL4649749
8.18	IC50	6.6	nM	CHEMBL4634952
8.15	IC50	7	nM	CHEMBL2419814
8.15	IC50	7	nM	CHEMBL2064166
8.15	IC50	7	nM	CHEMBL3770896
8.15	IC50	7	nM	CHEMBL4862347
8.14	IC50	7.3	nM	CHEMBL2064166
8.12	IC50	7.6	nM	CHEMBL4845987
8.10	IC50	8	nM	CHEMBL3353547
8.08	IC50	8.3	nM	CHEMBL4854759
8.08	IC50	8.3	nM	CHEMBL4863536
8.07	IC50	8.5	nM	CHEMBL4637132

PubChem BioAssay actives

252 with measured affinity, of 427 total; 50 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
3-cyclopropyl-3-[[2-fluoro-4-(3-fluoro-4-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0003	uM
3-[[2-fluoro-4-(3-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0005	uM
3-[[4-(4-methylphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0005	uM
3-[[4-(4-fluorophenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0007	uM
3-[[4-(3-methoxyphenyl)-2-(trifluoromethyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0008	uM
3-[[4-(3-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0009	uM
3-[[4-(4-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0009	uM
3-[[4-(2,3-dimethoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0009	uM
3-[(2-bromo-4-phenoxyphenyl)methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0010	uM
3-[(4-phenoxyphenyl)methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0011	uM
3-[[4-(3-phenylmethoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0014	uM
N-(1-cyano-3-methylazetidin-3-yl)-4-(3-methoxyphenyl)benzamide	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0016	uM
3-[[4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0016	uM
3-[5-(3-fluoro-4-methoxyphenyl)-1,3-dihydroisoindol-2-yl]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0016	uM
3-[[4-(3-methoxyphenyl)phenyl]methoxy]-3-methylazetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0018	uM
N-(3-isothiocyanatocyclobutyl)-4-(4-methoxyphenyl)benzenesulfonamide	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0023	uM
3-[[2-(4-cyanophenyl)-4-phenoxyphenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0025	uM
3-[(4-phenylphenyl)methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0028	uM
3-[[2-methoxy-4-(3-methoxyphenyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0028	uM
1-[4-(3-methoxyphenyl)phenyl]sulfonyl-1,6-diazaspiro[3.3]heptane-6-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0028	uM
4-(3-fluoro-4-methoxyphenyl)-N-(3-isothiocyanatocyclobutyl)benzenesulfonamide	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0032	uM
N-(1-cyano-3-methylazetidin-3-yl)-4-(3-methoxyphenyl)benzenesulfonamide	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0032	uM
3-[(4-phenylphenyl)methoxymethyl]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0034	uM
5-[3-fluoro-4-[(3-isothiocyanatocyclobutyl)oxymethyl]phenyl]-2,3-dihydro-1-benzofuran	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0045	uM
3-[[2-fluoro-4-(3-fluoro-4-methoxyphenyl)phenyl]methoxy]-3-pyridin-3-ylazetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0046	uM
[(2S)-nonan-2-yl] N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	767870: Inhibition of C-terminal His-6-tagged recombinant human spleen NAAA enzyme expressed in HEK293 cells	ic50	0.0050	uM
5-cyclohexylpentyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	767870: Inhibition of C-terminal His-6-tagged recombinant human spleen NAAA enzyme expressed in HEK293 cells	ic50	0.0050	uM
3-[[2-(4-methoxyphenyl)-4-phenoxyphenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0057	uM
3-[[4-(2-methoxy-3-pyridinyl)phenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0058	uM
4-cyclohexylbutyl N-[(2S,3S)-2-methyl-1-(2-methylsulfonylphenoxy)-4-oxoazetidin-3-yl]carbamate	1435887: Inhibition of recombinant human spleen NAAA expressed in HEK293 cells using PAMCA as substrate preincubated for 10 mins followed by substrate addition measured after 50 mins by fluorescence assay	ic50	0.0060	uM
4-cyclohexylbutyl N-[(2S,3S)-2-methyl-1-(4-methylsulfonylphenoxy)-4-oxoazetidin-3-yl]carbamate	1435887: Inhibition of recombinant human spleen NAAA expressed in HEK293 cells using PAMCA as substrate preincubated for 10 mins followed by substrate addition measured after 50 mins by fluorescence assay	ic50	0.0060	uM
4-cyclohexylbutyl N-[(2S,3S)-2-methyl-1-(3-methylsulfonylphenyl)-4-oxoazetidin-3-yl]carbamate	1650222: Inhibition of NAAA (unknown origin)	ic50	0.0060	uM
4-cyclohexylbutyl N-[(3S)-2-oxoazetidin-3-yl]carbamate	1651771: Inhibition of human NAAA	ic50	0.0060	uM
3-[[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]methoxy]-3-phenylazetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0061	uM
N-(3-isothiocyanatocyclobutyl)-5-(4-methoxyphenyl)pyridine-2-sulfonamide	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0063	uM
1-[4-(3-methoxyphenyl)benzoyl]-1,6-diazaspiro[3.3]heptane-6-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0065	uM
3-[[2-(2-cyanophenyl)-4-phenoxyphenyl]methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0066	uM
[4-(4-methoxyphenyl)phenyl] N-(3-isothiocyanatocyclobutyl)carbamate	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0070	uM
5-phenylpentyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	1776367: Inhibition of NAAA (unknown origin)	ic50	0.0070	uM
(4-phenylphenyl)methyl N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate	1776367: Inhibition of NAAA (unknown origin)	ic50	0.0070	uM
(4-butylphenyl)methyl N-[(3S)-2-oxoazetidin-3-yl]carbamate	1281616: Inhibition of recombinant human NAAA expressed in HEK293 cells after 30 mins by UPLC/MS analysis	ic50	0.0070	uM
N-(3-isothiocyanatocyclobutyl)-5-(4-methoxyphenyl)pyridine-2-carboxamide	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0076	uM
5-(1-benzofuran-5-yl)-2-[(3-isothiocyanatocyclobutyl)oxymethyl]pyridine	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0083	uM
3-isothiocyanato-1-(6-phenylhexyl)azetidine	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0083	uM
3-[(4-phenoxy-2-phenylphenyl)methoxy]azetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0085	uM
5-[3-fluoro-4-[(3-isothiocyanatocyclobutyl)oxymethyl]phenyl]-1,3-benzodioxole	1776314: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay	ic50	0.0088	uM
3-[6-(3-chlorophenyl)hexanoyl]-1,3-oxazolidin-2-one	1776367: Inhibition of NAAA (unknown origin)	ic50	0.0090	uM
3-[[4-(3-methoxyphenyl)phenyl]methoxy]-3-phenylazetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0091	uM
3-[[4-(1,3-benzodioxol-5-yl)phenyl]methoxy]-3-phenylazetidine-1-carbonitrile	1650206: Inhibition of activated human NAAA using fluorogenic PAMCA and N-4-methylcoumarin as substrate incubated for 90 mins by fluorescence based assay	ic50	0.0092	uM
4-cyclohexylbutyl N-[(2S,3S)-2-methyl-1-(3-methylsulfonylphenoxy)-4-oxoazetidin-3-yl]carbamate	1435887: Inhibition of recombinant human spleen NAAA expressed in HEK293 cells using PAMCA as substrate preincubated for 10 mins followed by substrate addition measured after 50 mins by fluorescence assay	ic50	0.0100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
methylselenic acid	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzene	decreases expression	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Thimerosal	increases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Zinc	increases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

65 unique, capped per target: 65 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1068364	Binding	Inhibition of human recombinant NAAA expressed in human HEK293 cells assessed as conversion of [1,2-14C]palmitoylethanolamine to [1,2-14C]ethanolamine by liquid scintillation counting	Synthesis and biological evaluation of new potential inhibitors of N-acylethanolamine hydrolyzing acid amidase. — Bioorg Med Chem Lett

Cellosaurus cell lines

16 cell lines: 16 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0179	BT-474	Cancer cell line	Female
CVCL_4V65	BT474-5FU[r]	Cancer cell line	Female
CVCL_4Y08	BT-474/CMV-Luc	Cancer cell line	Female
CVCL_A2GH	LR-BT474	Cancer cell line	Female
CVCL_A4AK	BT-474 Tam2	Cancer cell line	Female
CVCL_A4CL	BT-474 Ecadherin EmGFP	Cancer cell line	Female
CVCL_AQ07	BT-474 Clone 5	Cancer cell line	Female
CVCL_AR86	BT-474 Tam1	Cancer cell line	Female
CVCL_AR96	BT-474 EEI	Cancer cell line	Female
CVCL_C9CU	BT-474-Luc2	Cancer cell line	Female

Clinical trials (associated diseases)

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