NAA40

Summary

NAA40 (N-alpha-acetyltransferase 40, NatD catalytic subunit, HGNC:25845) is a protein-coding gene on chromosome 11q13.1, encoding N-alpha-acetyltransferase 40 (Q86UY6). N-alpha-acetyltransferase that specifically mediates the acetylation of the N-terminal residues of histones H4 and H2A.

Enables histone H2A acetyltransferase activity; histone H4 acetyltransferase activity; and protein N-terminal-serine acetyltransferase activity. Predicted to be involved in chromatin remodeling. Predicted to act upstream of or within lipid metabolic process. Located in centriolar satellite; cytosol; and nucleoplasm.

Source: NCBI Gene 79829 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• MANE Select transcript: NM_024771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25845
Approved symbol	NAA40
Name	N-alpha-acetyltransferase 40, NatD catalytic subunit
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13848
Ensembl gene	ENSG00000110583
Ensembl biotype	protein_coding
OMIM	619999
Entrez	79829

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000338447, ENST00000377793, ENST00000534965, ENST00000536939, ENST00000539656, ENST00000542163, ENST00000542633, ENST00000544138, ENST00000544194, ENST00000545161, ENST00000861922, ENST00000861923, ENST00000861924, ENST00000954954, ENST00000954955, ENST00000954956

RefSeq mRNA: 2 — MANE Select: NM_024771 NM_001300800, NM_024771

CCDS: CCDS73311, CCDS8053

Canonical transcript exons

ENST00000377793 — 8 exons

Exon	Start	End
ENSE00002205887	63954338	63957319
ENSE00002229974	63939002	63939102
ENSE00003472420	63952238	63952333
ENSE00003533104	63952407	63952565
ENSE00003549500	63946951	63947003
ENSE00003573788	63953972	63954049
ENSE00003583162	63952756	63952839
ENSE00003614471	63945840	63945935

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2815 / max 129.0709, expressed in 1784 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114844	12.6055	1782
114845	0.6760	407

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.54	gold quality
tendon of biceps brachii	UBERON:0008188	92.10	gold quality
apex of heart	UBERON:0002098	90.71	gold quality
pituitary gland	UBERON:0000007	90.29	gold quality
adenohypophysis	UBERON:0002196	90.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.99	gold quality
cerebellar hemisphere	UBERON:0002245	88.98	gold quality
cerebellar cortex	UBERON:0002129	88.90	gold quality
right lobe of thyroid gland	UBERON:0001119	88.20	gold quality
cerebellum	UBERON:0002037	88.04	gold quality
metanephros cortex	UBERON:0010533	87.97	gold quality
left lobe of thyroid gland	UBERON:0001120	87.95	gold quality
cortical plate	UBERON:0005343	87.84	gold quality
right uterine tube	UBERON:0001302	87.81	gold quality
thyroid gland	UBERON:0002046	87.54	gold quality
jejunal mucosa	UBERON:0000399	87.33	gold quality
mucosa of transverse colon	UBERON:0004991	87.29	gold quality
right testis	UBERON:0004534	87.26	gold quality
left adrenal gland cortex	UBERON:0035825	87.25	gold quality
choroid plexus epithelium	UBERON:0003911	87.24	gold quality
ganglionic eminence	UBERON:0004023	87.08	gold quality
left testis	UBERON:0004533	87.04	gold quality
left adrenal gland	UBERON:0001234	86.94	gold quality
duodenum	UBERON:0002114	86.94	gold quality
right adrenal gland	UBERON:0001233	86.87	gold quality
right atrium auricular region	UBERON:0006631	86.87	gold quality
bronchial epithelial cell	CL:0002328	86.85	gold quality
ventricular zone	UBERON:0003053	86.72	gold quality
right adrenal gland cortex	UBERON:0035827	86.39	gold quality
granulocyte	CL:0000094	86.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting NAA40, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290

Literature-anchored findings (GeneRIF, showing 7)

• a novel protein acetyltransferase Patt1 might be involved in the development of hepatocellular carcinoma (PMID:19695338)
• Results strongly suggest that human Naa40p/NatD is conserved from yeast. Thus, the NATs of all classes of N-terminally acetylated proteins in humans now appear to be accounted for. (PMID:21935442)
• The knowledge of detailed molecular architecture of Patt1 is not only the key to understanding its mechanistic functional properties but it also opens the possibility of rational drug and protein design experiments (PMID:24248912)
• findings reveal an anti-apoptotic role for Naa40 and exhibit its potential as a therapeutic target in colorectal cancers. (PMID:26666750)
• NatD-mediated acetylation of histone H4 serine 1 competes with phosphorylation by CK2alpha at the same residue, leading to the upregulation of Slug and lung cancer progression. (PMID:29030587)
• The findings strengthen the importance of NAA40 to maintain colorectal cancer cell growth. We show that NAA40 oncogenic properties stimulate the global levels of H4R3me2s by transcriptionally activating PRMT5 methyltransferase which in turn modulates the expression of key downstream cancer-related genes. (PMID:30858358)
• Effects of Oncohistone Mutations and PTM Crosstalk on the N-Terminal Acetylation Activities of NatD. (PMID:35044762)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	naa40	ENSDARG00000024109
danio_rerio	NAA40	ENSDARG00000090570
mus_musculus	Naa40	ENSMUSG00000024764
rattus_norvegicus	Naa40	ENSRNOG00000021179
drosophila_melanogaster	Naa40	FBGN0039687
caenorhabditis_elegans		WBGENE00021392

Protein

Protein identifiers

N-alpha-acetyltransferase 40 — Q86UY6 (reviewed: Q86UY6)

Alternative names: N-acetyltransferase 11, N-alpha-acetyltransferase D, Protein acetyltransferase 1

All UniProt accessions (4): Q86UY6, F5GXF6, F5GY41, F5H2C9

UniProt curated annotations — full annotation on UniProt →

Function. N-alpha-acetyltransferase that specifically mediates the acetylation of the N-terminal residues of histones H4 and H2A. In contrast to other N-alpha-acetyltransferase, has a very specific selectivity for histones H4 and H2A N-terminus and specifically recognizes the ‘Ser-Gly-Arg-Gly sequence’. Acts as a negative regulator of apoptosis. May play a role in hepatic lipid metabolism.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed; with the highest expression level in liver and the lowest expression in brain (at protein level).

Induction. Down-regulated in hepatocellular carcinoma tissues.

Similarity. Belongs to the acetyltransferase family. NAA40 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86UY6-1	1	yes
Q86UY6-3	2
Q86UY6-4	3

RefSeq proteins (2): NP_001287729, NP_079047* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR039949	NAA40	Family

Pfam: PF00583

Enzyme classification (BRENDA):

• EC 2.3.1.257 — N-terminal L-serine Nalpha-acetyltransferase NatD (BRENDA: 5 organisms, 15 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• N-terminal L-seryl-[histone H4] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[histone H4] + CoA + H(+) (RHEA:50596)
• N-terminal L-seryl-[histone H2A] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-seryl-[histone H2A] + CoA + H(+) (RHEA:50600)

UniProt features (48 total): mutagenesis site 11, binding site 9, helix 9, strand 9, splice variant 2, turn 2, initiator methionine 1, chain 1, site 1, lipid moiety-binding region 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7KPU	X-RAY DIFFRACTION	1.43
7KD7	X-RAY DIFFRACTION	1.44
4U9V	X-RAY DIFFRACTION	1.78
4U9W	X-RAY DIFFRACTION	2.49
9SYR	ELECTRON MICROSCOPY	3.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UY6-F1	92.96	0.88

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 (1): 139 (essential for catalytic activity)

Ligand- & substrate-binding residues (9): 197; 211; 85; 127–129; 138; 140–142; 148–153; 174; 179

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (11):

Position	Phenotype
85	strongly reduced n-alpha-acetyltransferase activity.
90	strongly reduced n-alpha-acetyltransferase activity.
100	5 times reduced n-alpha-acetyltransferase activity.
127–129	strongly reduced n-alpha-acetyltransferase activity.
136	strongly reduced n-alpha-acetyltransferase activity.
136	slightly reduced n-alpha-acetyltransferase activity.
137	reduced n-alpha-acetyltransferase activity.
138	strongly reduced n-alpha-acetyltransferase activity.
139	abolished n-alpha-acetyltransferase activity.
174	does not affect n-alpha-acetyltransferase activity.
211	does not affect n-alpha-acetyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GGGACCA_MIR133A_MIR133B, TGGTGCT_MIR29A_MIR29B_MIR29C, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, ATACCTC_MIR202, chr11q13, CAGCAGG_MIR370, GOBP_LIPID_METABOLIC_PROCESS, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, GOBP_CHROMATIN_REMODELING, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, SENESE_HDAC3_TARGETS_DN, KIM_WT1_TARGETS_DN, GOMF_ACETYLTRANSFERASE_ACTIVITY, GOMF_HISTONE_H4_ACETYLTRANSFERASE_ACTIVITY

GO Biological Process (2): lipid metabolic process (GO:0006629), chromatin remodeling (GO:0006338)

GO Molecular Function (7): histone H4 acetyltransferase activity (GO:0010485), histone H2A acetyltransferase activity (GO:0043998), protein N-terminal-serine acetyltransferase activity (GO:1990189), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), centriolar satellite (GO:0034451), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
histone acetyltransferase activity	2
primary metabolic process	1
chromatin organization	1
protein-N-terminal amino-acid acetyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
centrosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2411 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAA40	NAA50	Q9GZZ1	907
NAA40	NAA60	Q9H7X0	871
NAA40	NAA20	P61599	846
NAA40	NAA10	P41227	810
NAA40	NAA30	Q147X3	810
NAA40	NAA15	Q9BXJ9	796
NAA40	NAA80	Q93015	794
NAA40	NAA35	Q5VZE5	717
NAA40	NAA11	Q9BSU3	708
NAA40	NAA25	Q14CX7	677
NAA40	HYPK	Q9NX55	597
NAA40	NAA16	Q6N069	585
NAA40	GLYATL1	Q969I3	543
NAA40	H2AC20	Q16777	455
NAA40	H2AC19	P20670	455

IntAct

23 interactions, top by confidence:

A	B	Type	Score
KIF5B	KLC1	psi-mi:“MI:0914”(association)	0.730
BTF3	NAA40	psi-mi:“MI:0915”(physical association)	0.560
NAA40	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGA1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
HMGN2	NSD2	psi-mi:“MI:0914”(association)	0.350
HMGN5	SMCHD1	psi-mi:“MI:0914”(association)	0.350
KLC2	KIF5C	psi-mi:“MI:0914”(association)	0.350
KLC4	KIF5C	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
HNRNPCL2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
NAA40	TMOD1	psi-mi:“MI:0914”(association)	0.350
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
BTF3	NAA40	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1010): NAA40 (Affinity Capture-MS), NAA40 (Co-fractionation), NAA40 (Co-fractionation), NAA40 (Affinity Capture-MS), NAA40 (Affinity Capture-MS), NAA40 (Affinity Capture-MS), UBA52 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), ANGEL2 (Affinity Capture-MS), SUPT16H (Affinity Capture-MS), METAP1 (Affinity Capture-MS), XPC (Affinity Capture-MS), TPP2 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS), H2AFY (Affinity Capture-MS)

ESM2 similar proteins: A0A385XJE6, A0MQH0, O85343, P03009, P03835, P09130, P0CE49, P0CE50, P0CE51, P0CE52, P0CE53, P0CE54, P0CE55, P0CE56, P0CE57, P0CE58, P0CE59, P0CE60, P0CE61, P0CE62, P0CE63, P0CE64, P0CE65, P11029, P21189, P22708, P24175, P37742, P76071, P77688, P77748, Q00840, Q12882, Q14353, Q25BN1, Q28007, Q28943, Q2TBQ3, Q32J95, Q41141

Diamond homologs: Q568K5, Q6NUH2, Q86UY6, Q8VE10, Q9USH6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
RHO GTPase Effectors	5	16.2×	9e-04
Membrane Trafficking	5	8.8×	3e-03
Adaptive Immune System	6	8.5×	2e-03
Vesicle-mediated transport	5	8.3×	4e-03
Signaling by Rho GTPases	5	8.1×	4e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	5	8.0×	4e-03
Viral Infection Pathways	5	7.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1361 predictions. Top by Δscore:

Variant	Effect	Δscore
11:63939099:GGGG:G	donor_gain	1.0000
11:63939100:GGG:G	donor_gain	1.0000
11:63939100:GGGG:G	donor_gain	1.0000
11:63939101:GG:G	donor_gain	1.0000
11:63939101:GGG:G	donor_gain	1.0000
11:63939102:GG:G	donor_gain	1.0000
11:63939104:T:A	donor_loss	1.0000
11:63945836:GCA:G	acceptor_loss	1.0000
11:63945837:CA:C	acceptor_loss	1.0000
11:63945838:A:AG	acceptor_gain	1.0000
11:63945838:A:G	acceptor_loss	1.0000
11:63945839:G:GA	acceptor_gain	1.0000
11:63945839:GA:G	acceptor_gain	1.0000
11:63945839:GAGA:G	acceptor_gain	1.0000
11:63945839:GAGAA:G	acceptor_gain	1.0000
11:63945934:GG:G	donor_gain	1.0000
11:63945935:G:GT	donor_gain	1.0000
11:63952334:G:GG	donor_gain	1.0000
11:63952500:C:G	donor_gain	1.0000
11:63952753:TA:T	acceptor_loss	1.0000
11:63952754:A:AG	acceptor_gain	1.0000
11:63952754:AG:A	acceptor_loss	1.0000
11:63952755:G:GT	acceptor_gain	1.0000
11:63952755:GC:G	acceptor_gain	1.0000
11:63952755:GCT:G	acceptor_gain	1.0000
11:63952755:GCTAT:G	acceptor_gain	1.0000
11:63952836:ACAG:A	donor_gain	1.0000
11:63952838:AGGT:A	donor_loss	1.0000
11:63952839:GGTAA:G	donor_loss	1.0000
11:63952840:G:GG	donor_gain	1.0000

AlphaMissense

1586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:63952309:T:C	L76P	1.000
11:63952429:T:A	W92R	1.000
11:63952429:T:C	W92R	1.000
11:63952431:G:C	W92C	1.000
11:63952431:G:T	W92C	1.000
11:63952446:A:C	K97N	1.000
11:63952446:A:T	K97N	1.000
11:63952529:G:C	R125P	1.000
11:63952794:G:A	G150D	1.000
11:63952800:G:A	G152E	1.000
11:63945928:C:A	A32D	0.999
11:63946990:T:G	Y48D	0.999
11:63952252:T:A	I57N	0.999
11:63952408:T:C	Y85H	0.999
11:63952417:A:C	S88R	0.999
11:63952419:C:A	S88R	0.999
11:63952419:C:G	S88R	0.999
11:63952423:T:A	W90R	0.999
11:63952423:T:C	W90R	0.999
11:63952430:G:C	W92S	0.999
11:63952444:A:G	K97E	0.999
11:63952472:C:A	A106D	0.999
11:63952481:T:C	L109P	0.999
11:63952514:C:A	A120D	0.999
11:63952526:T:C	F124S	0.999
11:63952531:T:C	F126L	0.999
11:63952532:T:C	F126S	0.999
11:63952533:T:A	F126L	0.999
11:63952533:T:G	F126L	0.999
11:63952559:T:C	L135P	0.999

dbSNP variants (sampled 300 via entrez): RS1000363486 (11:63949568 T>C), RS1000381586 (11:63943993 T>G), RS1000387467 (11:63949845 C>T), RS1000517014 (11:63943348 A>G), RS1000566246 (11:63939312 C>T), RS1000673117 (11:63937770 G>A,T), RS1000715016 (11:63945401 C>T), RS1000931779 (11:63939006 G>A,T), RS1001054514 (11:63943615 A>C), RS1001175006 (11:63944435 A>G), RS1001204603 (11:63944732 G>A), RS1001333055 (11:63956058 G>A), RS1001655864 (11:63954729 C>T), RS1001773004 (11:63938739 G>A,T), RS1001895055 (11:63950035 T>C)

Disease associations

OMIM: gene MIM:619999 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010204_70	Low density lipoprotein cholesterol levels	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523373 (SINGLE PROTEIN)

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

ChEMBL bioactivities

26 potent at pChembl≥5 of 26 total, top 26 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.21	Ki	0.61	nM	CHEMBL5081275
9.00	Ki	1	nM	CHEMBL5081275
8.68	Ki	2.1	nM	CHEMBL5077025
8.43	Ki	3.7	nM	CHEMBL5090533
8.39	IC50	4.1	nM	CHEMBL5081275
8.36	Ki	4.4	nM	CHEMBL5093444
8.21	Ki	6.2	nM	CHEMBL5075935
8.15	IC50	7.1	nM	CHEMBL5077025
8.08	Ki	8.4	nM	CHEMBL5083117
8.06	Ki	8.7	nM	CHEMBL5077510
7.80	IC50	16	nM	CHEMBL5090533
7.70	IC50	20	nM	CHEMBL5093444
7.60	IC50	25	nM	CHEMBL5075935
7.57	IC50	27	nM	CHEMBL5075404
7.54	IC50	29	nM	CHEMBL5090533
7.50	IC50	32	nM	CHEMBL5077510
7.46	IC50	35	nM	CHEMBL5093444
7.46	IC50	35	nM	CHEMBL5077510
7.40	IC50	40	nM	CHEMBL5081275
7.40	IC50	40	nM	CHEMBL5083117
7.39	IC50	41	nM	CHEMBL5075935
7.39	IC50	41	nM	CHEMBL5083117
7.32	IC50	48	nM	CHEMBL5075404
7.32	IC50	48	nM	CHEMBL5077025
6.66	IC50	218	nM	CHEMBL5088740
5.36	Ki	4400	nM	CHEMBL5075404

PubChem BioAssay actives

26 with measured affinity, of 38 total; 9 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
[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [4-[[3-[2-[3-[[(2S)-1-[[2-[[(2S)-5-(diaminomethylideneamino)-1-[[2-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1811941: Competitive inhibition of human NatD using various concentration of human H4 peptide and fixed [14C]acetyl-CoA as substrate measured after 13 mins radioactive assay	ki	0.0006	uM
[[4-[[3-[2-[3-[[(2S)-1-[[2-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811939: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA by Morrison’s quadratic equation analysis	ki	0.0021	uM
[[4-[[3-[2-[2-[[(2S)-1-[[2-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811939: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA by Morrison’s quadratic equation analysis	ki	0.0037	uM
[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [4-[[3-[2-[2-[[(2S)-1-[[2-[[(2S)-5-(diaminomethylideneamino)-1-[[2-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1811939: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA by Morrison’s quadratic equation analysis	ki	0.0044	uM
[[4-[[3-[2-[2-[[(2S)-1-[[2-[[(2S)-1-[[2-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811939: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA by Morrison’s quadratic equation analysis	ki	0.0062	uM
[[4-[[3-[2-[3-[[(2S)-1-[[2-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811939: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA by Morrison’s quadratic equation analysis	ki	0.0084	uM
[[4-[[3-[2-[3-[[(2S)-1-[[2-[[(2S)-1-[[2-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811939: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA by Morrison’s quadratic equation analysis	ki	0.0087	uM
[[4-[[3-[2-[2-[[(2S)-1-[[2-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811938: Inhibition of human NatD using H4-8 peptide substrate at 4 times Km value and AcCoA measured after 30 min incubation by fluorescence assay	ic50	0.0270	uM
[[4-[[3-[2-[2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-hydroxyphosphoryl] [(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methyl hydrogen phosphate	1811937: Inhibition of human NatD using H4-8 peptide substrate at Km value and AcCoA measured after 30 min incubation by fluorescence assay	ic50	0.2180	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4325444	Binding	Inhibition of NatD (unknown origin)	Discovery of Highly Potent, Selective, and Orally Efficacious p300/CBP Histone Acetyltransferases Inhibitors. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ76	HAP1 NAA40 (-) 1	Cancer cell line	Male
CVCL_SZ77	HAP1 NAA40 (-) 2	Cancer cell line	Male
CVCL_SZ78	HAP1 NAA40 (-) 3	Cancer cell line	Male
CVCL_SZ79	HAP1 NAA40 (-) 4	Cancer cell line	Male
CVCL_SZ80	HAP1 NAA40 (-) 5	Cancer cell line	Male
CVCL_SZ81	HAP1 NAA40 (-) 6	Cancer cell line	Male

Clinical trials (associated diseases)

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