NAT10

Summary

NAT10 (N-acetyltransferase 10, HGNC:29830) is a protein-coding gene on chromosome 11p13, encoding RNA cytidine acetyltransferase (Q9H0A0). RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs. It is a common-essential gene (DepMap: required in 98.5% of cancer cell lines).

The protein encoded by this gene is an RNA cytidine acetyltransferase involved in histone acetylation, tRNA acetylation, the biosynthesis of 18S rRNA, and the enhancement of nuclear architecture and chromatin organization.

Source: NCBI Gene 55226 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 164 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_024662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29830
Approved symbol	NAT10
Name	N-acetyltransferase 10
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	hALP, FLJ10774, FLJ12179, NET43, KIAA1709, Kre33
Ensembl gene	ENSG00000135372
Ensembl biotype	protein_coding
OMIM	609221
Entrez	55226

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000257829, ENST00000527971, ENST00000529523, ENST00000530017, ENST00000531159, ENST00000531723, ENST00000532503, ENST00000532555, ENST00000534509, ENST00000891108, ENST00000891109, ENST00000891110, ENST00000935946, ENST00000935947, ENST00000946066

RefSeq mRNA: 2 — MANE Select: NM_024662 NM_001144030, NM_024662

CCDS: CCDS44568, CCDS7889

Canonical transcript exons

ENST00000257829 — 29 exons

Exon	Start	End
ENSE00000709838	34141719	34141817
ENSE00000709855	34134319	34134420
ENSE00000709857	34132125	34132221
ENSE00000709869	34118396	34118503
ENSE00000709871	34118180	34118294
ENSE00000824415	34131381	34131531
ENSE00000918387	34142275	34142348
ENSE00000918389	34141089	34141208
ENSE00000918390	34140400	34140572
ENSE00000918391	34139385	34139495
ENSE00000918392	34139191	34139287
ENSE00000918393	34136978	34137026
ENSE00000918394	34136642	34136775
ENSE00000918395	34135175	34135291
ENSE00000918396	34134512	34134586
ENSE00000918401	34130813	34130937
ENSE00000918402	34127463	34127599
ENSE00000918403	34124302	34124400
ENSE00000918404	34123762	34123855
ENSE00000918405	34122459	34122592
ENSE00000918408	34115823	34115884
ENSE00000918409	34113716	34113838
ENSE00001004248	34146084	34146908
ENSE00001279217	34133026	34133142
ENSE00002180345	34105629	34105792
ENSE00003547282	34112052	34112223
ENSE00003598270	34143445	34143528
ENSE00003611265	34108211	34108333
ENSE00003642622	34108742	34108833

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.6176 / max 351.3502, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113707	25.9459	1809
113708	9.1921	1739
113709	1.6440	953
113706	0.8356	518

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.84	gold quality
skin of leg	UBERON:0001511	91.71	gold quality
adrenal tissue	UBERON:0018303	91.70	gold quality
skin of abdomen	UBERON:0001416	91.61	gold quality
ventricular zone	UBERON:0003053	91.47	gold quality
right ovary	UBERON:0002118	91.07	gold quality
left ovary	UBERON:0002119	90.72	gold quality
calcaneal tendon	UBERON:0003701	90.40	gold quality
body of pancreas	UBERON:0001150	90.34	gold quality
zone of skin	UBERON:0000014	90.21	gold quality
tonsil	UBERON:0002372	90.11	gold quality
right uterine tube	UBERON:0001302	89.81	gold quality
tibial nerve	UBERON:0001323	89.65	gold quality
ovary	UBERON:0000992	89.44	gold quality
lower esophagus mucosa	UBERON:0035834	89.38	gold quality
lymph node	UBERON:0000029	89.35	gold quality
adenohypophysis	UBERON:0002196	89.35	gold quality
left uterine tube	UBERON:0001303	89.33	gold quality
esophagus mucosa	UBERON:0002469	89.26	gold quality
right adrenal gland cortex	UBERON:0035827	89.26	gold quality
gastrocnemius	UBERON:0001388	89.20	gold quality
body of uterus	UBERON:0009853	89.20	gold quality
adrenal gland	UBERON:0002369	89.19	gold quality
right adrenal gland	UBERON:0001233	89.13	gold quality
left adrenal gland cortex	UBERON:0035825	89.11	gold quality
cerebellar hemisphere	UBERON:0002245	89.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.09	gold quality
granulocyte	CL:0000094	89.06	gold quality
cerebellar cortex	UBERON:0002129	89.00	gold quality
muscle of leg	UBERON:0001383	88.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

23 targeting NAT10, 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-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-10401-5P	99.99	65.79	948
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-3672	94.46	65.67	646
HSA-MIR-6864-3P	94.46	65.97	625

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The investigation suggested that hALP influences the activity of histone acetylation and could up-regulate telomerase activity through transactivation of hTERT promoter. (PMID:14592445)
• The above results suggested that NAT10 could be involved in DNA damage response and increased cellular resistance to genotoxicity. (PMID:17180247)
• chromosome de-condensation needs the function of an inner nuclear membrane (INM) protein hsSUN1 and a membrane-associated histone acetyltransferase (HAT), hALP. (PMID:17631499)
• hALP is a nucleolar protein, and the nucleolar localization is mediated by its carboxy terminal domain. (PMID:18677378)
• NAT10 may play an important role in cell division through facilitating reformation of the nucleolus and midbody in the late phase of cell mitosis, and stabilization of microtubules. (PMID:19303003)
• we identified hALP, a histone acetyl-transferase as a novel t-UTP (PMID:21177859)
• The subcellular redistribution of NAT10 can be induced by decreases in GSK-3b activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome (PMID:24982245)
• NAT10 is an ATP-dependent RNA acetyltransferase responsible for formation of N(4)-acetylcytidine (ac(4)C) at position 1842 in the terminal helix of mammalian 18 S rRNA. (PMID:25411247)
• Identification of NAT10 as responsible for both 18S rRNA and leucine/serine tRNA acetylation. (PMID:25653167)
• NAT10 translocates to nucleoplasm to bind and acetylate p53 at K120 upon cellular stress. (PMID:26882543)
• NAT10 is acetylated in vivo and autoacetylated in vitro (PMID:27993683)
• Increased NAT10 expression levels are associated with shortened hepatocellular carcinoma (HCC) patient survival and correlated with mutant p53 levels. NAT10 upregulates mutant p53 level and might enhance its tumorigenic activity. Hence, it is proposed that NAT10 could be a potential prognostic and therapeutic candidate for p53-mutated HCC. (PMID:28859621)
• immunohistochemistry staining of NAT10 in hepatocellular carcinoma tissues demonstrates that the cytoplasmic NAT10 is correlated with poorer prognosis compared with nuclear NAT10, while the membranous NAT10 predicts the poorest clinical outcome of the patients. (PMID:29634924)
• High NAT10 expression is associated with Hutchinson-Gilford progeria syndrome by sequestering TNPO1 in the cytoplasm. (PMID:29970603)
• we demonstrate that the acetylation status of NAT10 is important for the anabolism-catabolism transition in response to energy stress, providing a novel mechanism by which nucleolar proteins control rRNA synthesis and autophagy in response to the cellular energy supply. (PMID:30165671)
• NAT10 upregulation indicates a poor prognosis in acute myeloid leukemia. (PMID:31279531)
• A role for MORC2 in regulating DNA damage-induced G2 checkpoint through NAT10-mediated acetylation. (PMID:32112098)
• Structural insights of human N-acetyltransferase 10 and identification of its potential novel inhibitors. (PMID:33723305)
• NAT10 promotes gastric cancer metastasis via N4-acetylated COL5A1. (PMID:33941767)
• Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication. (PMID:35743017)
• [Overexpression of NAT10 induced platinum drugs resistance in breast cancer cell]. (PMID:35754228)
• c-myc-mediated upregulation of NAT10 facilitates tumor development via cell cycle regulation in non-small cell lung cancer. (PMID:35834140)
• Regulatory roles of NAT10 in airway epithelial cell function and metabolism in pathological conditions. (PMID:35877022)
• N-acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4-acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA. (PMID:36209353)
• Acetyltransferase NAT10 regulates the Wnt/beta-catenin signaling pathway to promote colorectal cancer progression via ac[4]C acetylation of KIF23 mRNA. (PMID:36522719)
• Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression. (PMID:36609449)
• NAT10 promotes osteogenic differentiation of periodontal ligament stem cells by regulating VEGFA-mediated PI3K/AKT signaling pathway through ac4C modification. (PMID:36879181)
• NAT10 mediated mRNA acetylation modification patterns associated with colon cancer progression and microsatellite status. (PMID:36908042)
• NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression. (PMID:37156457)
• Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10. (PMID:37277492)
• NAT10-mediated ac4C tRNA modification promotes EGFR mRNA translation and gefitinib resistance in cancer. (PMID:37463108)
• NAT10-mediated N4-acetylcytidine mRNA modification regulates self-renewal in human embryonic stem cells. (PMID:37497776)
• N-acetyltransferase 10 promotes the progression of oral squamous cell carcinoma through N4-acetylcytidine RNA acetylation of MMP1 mRNA. (PMID:37705232)
• NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer. (PMID:37818745)
• N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK/ERK signaling pathway. (PMID:37914704)
• NAT10 promotes the tumorigenesis and progression of laryngeal squamous cell carcinoma through ac4C modification of FOXM1 mRNA. (PMID:37948132)
• NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation. (PMID:37955115)
• NAT10 Promotes Malignant Progression of Lung Cancer via the NF-kappaB Signaling Pathway. (PMID:38058058)
• Decreased expression of NAT10 in peripheral blood mononuclear cells from new-onset ankylosing spondylitis and its clinical significance. (PMID:38167491)
• N-acetyltransferase 10 regulates alphavirus replication via N4-acetylcytidine (ac4C) modi fi cation of the lymphocyte antigen six family member E (LY6E) mRNA. (PMID:38169284)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nat10	ENSDARG00000054259
mus_musculus	Nat10	ENSMUSG00000027185
rattus_norvegicus	Nat10	ENSRNOG00000008663
drosophila_melanogaster	l(1)G0020	FBGN0027330
caenorhabditis_elegans	nath-10	WBGENE00018866

Protein

Protein identifiers

RNA cytidine acetyltransferase — Q9H0A0 (reviewed: Q9H0A0)

Alternative names: 18S rRNA cytosine acetyltransferase, N-acetyltransferase 10, N-acetyltransferase-like protein

All UniProt accessions (3): E9PJN6, E9PMU0, Q9H0A0

UniProt curated annotations — full annotation on UniProt →

Function. RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs. Catalyzes ac4C modification of a broad range of mRNAs, enhancing mRNA stability and translation. mRNA ac4C modification is frequently present within wobble cytidine sites and promotes translation efficiency. Mediates the formation of ac4C at position 1842 in 18S rRNA. May also catalyze the formation of ac4C at position 1337 in 18S rRNA. Required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis. Catalyzes the formation of ac4C in serine and leucine tRNAs. Requires the tRNA-binding adapter protein THUMPD1 for full tRNA acetyltransferase activity but not for 18S rRNA acetylation. In addition to RNA acetyltransferase activity, also able to acetylate lysine residues of proteins, such as histones, microtubules, p53/TP53 and MDM2, in vitro. The relevance of the protein lysine acetyltransferase activity is however unsure in vivo. Activates telomerase activity by stimulating the transcription of TERT, and may also regulate telomerase function by affecting the balance of telomerase subunit assembly, disassembly, and localization. Involved in the regulation of centrosome duplication by acetylating CENATAC during mitosis, promoting SASS6 proteasome degradation. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with THUMPD1. Interacts with SUN1 (via N-terminus). Interacts with TERT.

Subcellular location. Nucleus. Nucleolus. Midbody.

Post-translational modifications. Acetylation at Lys-426 is required to activation of rRNA transcription. May be autoacetylated; however ability to autoacetylate in vivo requires additional evidences.

Activity regulation. Specifically inhibited by remodelin (4-[2-(2-cyclopentylidenehydrazinyl)-4-thiazolyl]-benzonitrile, monohydrobromide), a hydrobromide salt molecule. Remodelin can improve nuclear architecture, chromatin organization and fitness of cells from patients suffering from Hutchinson-Gilford progeria syndrome (HGPS); molecular mechanisms explaining the relation between NAT10 activity and nuclear architecture are however unclear.

Induction. Transcriptionally activated by genotoxic agents; possible role in DNA damage and induction of cellular resistance to genotoxic agents.

Similarity. Belongs to the RNA cytidine acetyltransferase family. NAT10 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0A0-1	1	yes
Q9H0A0-2	2

RefSeq proteins (2): NP_001137502, NP_078938* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR007807	TcmA/NAT10_helicase	Domain
IPR013562	TmcA/NAT10_N	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027992	tRNA_bind_dom	Domain
IPR032672	TmcA/NAT10/Kre33	Family
IPR033688	NAT10	Family

Pfam: PF05127, PF08351, PF13718, PF13725

Catalyzed reactions (Rhea), 3 shown:

• a cytidine in 18S rRNA + acetyl-CoA + ATP + H2O = an N(4)-acetylcytidine in 18S rRNA + ADP + phosphate + CoA + H(+) (RHEA:51424)
• a cytidine in tRNA + acetyl-CoA + ATP + H2O = an N(4)-acetylcytidine in tRNA + ADP + phosphate + CoA + H(+) (RHEA:53876)
• a cytidine in mRNA + acetyl-CoA + ATP + H2O = an N(4)-acetylcytidine in mRNA + ADP + phosphate + CoA + H(+) (RHEA:58480)

UniProt features (27 total): sequence conflict 6, modified residue 5, binding site 5, sequence variant 2, mutagenesis site 2, region of interest 2, chain 1, domain 1, splice variant 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9J3C	ELECTRON MICROSCOPY	2.9
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87
6VLA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0A0-F1	78.61	0.21

Functional residue map

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

Ligand- & substrate-binding residues (5): 287–296; 470; 629–631; 636–642; 725

Post-translational modifications (5): 426, 716, 934, 984, 987

Mutagenesis-validated functional residues (2):

Position	Phenotype
426	abolished acetylation.
641	abolished acetyltransferase activity, probably caused by impaired acetyl-coa binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 206 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_MATURATION_OF_SSU_RRNA, GOBP_TRNA_METABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, USF_C, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, ONKEN_UVEAL_MELANOMA_UP

GO Biological Process (15): rRNA modification (GO:0000154), tRNA wobble cytosine modification (GO:0002101), regulation of translation (GO:0006417), protein acetylation (GO:0006473), regulation of centrosome duplication (GO:0010824), negative regulation of telomere maintenance via telomerase (GO:0032211), ribosomal small subunit biogenesis (GO:0042274), positive regulation of translation (GO:0045727), tRNA acetylation (GO:0051391), rRNA acetylation involved in maturation of SSU-rRNA (GO:1904812), rRNA processing (GO:0006364), tRNA processing (GO:0008033), RNA modification (GO:0009451), rRNA metabolic process (GO:0016072), ribosome biogenesis (GO:0042254)

GO Molecular Function (13): tRNA binding (GO:0000049), RNA binding (GO:0003723), ATP binding (GO:0005524), N-acetyltransferase activity (GO:0008080), tRNA cytidine N4-acetyltransferase activity (GO:0051392), DNA polymerase binding (GO:0070182), mRNA cytidine N-acetyltransferase activity (GO:0106162), 18S rRNA cytidine N-acetyltransferase activity (GO:1990883), nucleotide binding (GO:0000166), 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 (8): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), nucleolus (GO:0005730), membrane (GO:0016020), midbody (GO:0030496), small-subunit processome (GO:0032040)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
N-acetyltransferase activity	3
cellular anatomical structure	3
translation	2
ribonucleoprotein complex biogenesis	2
ribosome biogenesis	2
RNA processing	2
RNA metabolic process	2
nuclear lumen	2
nuclear protein-containing complex	2
rRNA processing	1
RNA modification	1
tRNA wobble base modification	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
protein acylation	1
regulation of centrosome cycle	1
centrosome duplication	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
tRNA modification	1
RNA acetylation	1
maturation of SSU-rRNA	1
rRNA acetylation	1
rRNA metabolic process	1
tRNA metabolic process	1
macromolecule modification	1
RNA binding	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
acetyltransferase activity	1
catalytic activity, acting on a tRNA	1
enzyme binding	1
catalytic activity, acting on a nucleic acid	1
catalytic activity, acting on a rRNA	1

Protein interactions and networks

STRING

3700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAT10	CAPRIN1	Q14444	909
NAT10	UTP20	O75691	903
NAT10	ESCO1	Q5FWF5	850
NAT10	ESCO2	Q56NI9	839
NAT10	BYSL	Q13895	811
NAT10	EMG1	Q92979	786
NAT10	SUN1	O94901	784
NAT10	NOP14	P78316	782
NAT10	BMS1	Q14692	763
NAT10	UTP14A	Q9BVJ6	752
NAT10	RRP12	Q5JTH9	724
NAT10	AATF	Q9NY61	718
NAT10	DDX52	Q9Y2R4	716
NAT10	NOP58	Q9Y2X3	715
NAT10	DKC1	O60832	713

IntAct

216 interactions, top by confidence:

A	B	Type	Score
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
NAT10	THUMPD1	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NAT10	RPS2	psi-mi:“MI:0915”(physical association)	0.670
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
THUMPD1	YBX1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
ESR1		psi-mi:“MI:0914”(association)	0.460

BioGRID (473): NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Biochemical Activity), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), NAT10 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4BZI5, A0A1S4CB73, B0F481, D2HRF1, F4I933, F4IY62, F4JKB6, F4JVN6, O23324, O23553, O80585, O82043, O82768, P10349, P30706, P36428, P42898, Q01292, Q05758, Q0J6P7, Q10S55, Q2QTL0, Q39639, Q42713, Q43307, Q43822, Q43870, Q5I598, Q5U2Z5, Q60HE5, Q66GI4, Q75HE6, Q7Z3D6, Q80YD1, Q8BH86, Q8H0W0, Q8K224, Q8RWG3, Q8VYL1, Q944I4

Diamond homologs: O01757, P53914, P54008, P87115, Q55EJ3, Q8K224, Q9H0A0, Q9M2Q4, Q9W3C1, Q9XIK4, Q8U3G4, Q9KKJ5, Q9UZ78

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NAT10	“down-regulates quantity by destabilization”	MDM2	ubiquitination
NAT10	“up-regulates quantity by stabilization”	TP53	acetylation
NAT10	“up-regulates quantity by stabilization”	PARP1	acetylation
MORC2	“up-regulates activity”	NAT10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 218 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
Eukaryotic Translation Initiation	7	14.8×	1e-05
Cap-dependent Translation Initiation	7	14.8×	1e-05
SARS-CoV-1 modulates host translation machinery	7	14.8×	1e-05
Peptide chain elongation	17	14.8×	1e-13
Viral mRNA Translation	17	14.8×	1e-13
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	17	14.6×	1e-13
Formation of a pool of free 40S subunits	19	14.6×	1e-14
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	18	14.5×	4e-14

GO biological processes:

GO term	Partners	Fold	FDR
chromosome condensation	5	22.8×	3e-04
cytoplasmic translation	18	18.0×	8e-15
ribosomal large subunit biogenesis	6	14.4×	5e-04
ribosomal small subunit biogenesis	10	12.3×	2e-06
negative regulation of translation	11	11.7×	1e-06
translation	18	10.0×	2e-10
heterochromatin formation	7	9.7×	9e-04
regulation of alternative mRNA splicing, via spliceosome	7	9.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	3
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

4451 predictions. Top by Δscore:

Variant	Effect	Δscore
11:34107183:C:G	donor_gain	1.0000
11:34108209:A:AG	acceptor_gain	1.0000
11:34108210:G:GG	acceptor_gain	1.0000
11:34108210:GTAAT:G	acceptor_gain	1.0000
11:34108736:TGGCA:T	acceptor_loss	1.0000
11:34108737:GGCAG:G	acceptor_loss	1.0000
11:34108738:GCAGG:G	acceptor_loss	1.0000
11:34108739:CAG:C	acceptor_loss	1.0000
11:34108740:AGG:A	acceptor_loss	1.0000
11:34108740:AGGT:A	acceptor_gain	1.0000
11:34108741:GGTG:G	acceptor_gain	1.0000
11:34112221:CAG:C	donor_loss	1.0000
11:34112222:AGGT:A	donor_loss	1.0000
11:34112223:GGTG:G	donor_loss	1.0000
11:34112224:GTG:G	donor_loss	1.0000
11:34113713:CAGG:C	acceptor_loss	1.0000
11:34113713:CAGGA:C	acceptor_gain	1.0000
11:34113714:A:AG	acceptor_gain	1.0000
11:34113714:AG:A	acceptor_gain	1.0000
11:34113715:G:C	acceptor_loss	1.0000
11:34113715:G:GG	acceptor_gain	1.0000
11:34113715:GG:G	acceptor_gain	1.0000
11:34113715:GGAT:G	acceptor_gain	1.0000
11:34113839:G:A	donor_loss	1.0000
11:34113839:G:GG	donor_gain	1.0000
11:34113840:TAAG:T	donor_loss	1.0000
11:34115819:TTA:T	acceptor_loss	1.0000
11:34115820:TA:T	acceptor_loss	1.0000
11:34115821:A:AG	acceptor_gain	1.0000
11:34115821:AG:A	acceptor_gain	1.0000

AlphaMissense

6697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:34122544:G:A	G289E	1.000
11:34122547:A:T	K290I	1.000
11:34127506:T:C	L384P	1.000
11:34127521:A:C	E389A	1.000
11:34127521:A:T	E389V	1.000
11:34130820:G:C	G418R	1.000
11:34130848:T:C	L427P	1.000
11:34108294:A:C	R23S	0.999
11:34108294:A:T	R23S	0.999
11:34108802:T:A	W57R	0.999
11:34108802:T:C	W57R	0.999
11:34112194:G:C	G115R	0.999
11:34112195:G:A	G115D	0.999
11:34112195:G:T	G115V	0.999
11:34113758:G:A	E139K	0.999
11:34115884:G:T	R186M	0.999
11:34122528:G:C	A284P	0.999
11:34122529:C:A	A284D	0.999
11:34122537:G:A	G287R	0.999
11:34122537:G:C	G287R	0.999
11:34122538:G:A	G287E	0.999
11:34122541:G:C	R288P	0.999
11:34122543:G:A	G289R	0.999
11:34122543:G:C	G289R	0.999
11:34122544:G:T	G289V	0.999
11:34122546:A:C	K290Q	0.999
11:34122548:A:C	K290N	0.999
11:34122548:A:T	K290N	0.999
11:34122550:C:T	S291F	0.999
11:34122561:G:A	G295R	0.999

dbSNP variants (sampled 300 via entrez): RS1000007791 (11:34126013 C>T), RS1000019698 (11:34114547 T>C), RS1000205970 (11:34123535 C>T), RS1000252234 (11:34120738 G>A), RS1000376274 (11:34107292 A>G), RS1000402157 (11:34131169 A>G), RS1000592705 (11:34119445 C>A), RS1000621047 (11:34131002 G>A), RS1000868952 (11:34126315 G>C), RS1000881534 (11:34136667 T>C), RS1000968390 (11:34112265 G>A), RS1001176491 (11:34125190 T>G), RS1001251556 (11:34136972 T>G), RS1001314613 (11:34103702 C>G), RS1001325858 (11:34136905 C>G,T)

Disease associations

OMIM: gene MIM:609221 | 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
GCST009391_1572	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010516	orotic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105935 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,596 (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
CHEMBL274654	ORANTINIB	3	3,596

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.52	Kd	0.302	nM	CHEMBL3752910
9.52	ED50	0.302	nM	CHEMBL3752910
6.63	Kd	235.2	nM	CHEMBL5653589
6.63	ED50	235.2	nM	CHEMBL5653589
5.91	Kd	1240	nM	ORANTINIB

PubChem BioAssay actives

3 with measured affinity, of 256 total; 3 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148826: Binding affinity to human NAT10 incubated for 45 mins by Kinobead based pull down assay	kd	0.0003	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148826: Binding affinity to human NAT10 incubated for 45 mins by Kinobead based pull down assay	kd	0.2352	uM
3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid	1425083: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-(4-cyanophenyl)-2-(2-cyclopentylidenehydrazinyl)thiazole	decreases activity, decreases expression	2
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	affects reaction, increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	affects expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	affects response to substance	1
idelalisib	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, 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	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases 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
CHEMBL3991796	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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