NAA50

Summary

NAA50 (N-alpha-acetyltransferase 50, NatE catalytic subunit, HGNC:29533) is a protein-coding gene on chromosome 3q13.31, encoding N-alpha-acetyltransferase 50 (Q9GZZ1). N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables histone H4 acetyltransferase activity and protein-N-terminal amino-acid acetyltransferase activity. Involved in N-terminal protein amino acid acetylation; establishment of mitotic sister chromatid cohesion; and mitotic sister chromatid cohesion, centromeric. Located in cytosol and nucleolus. Part of NatA complex.

Source: NCBI Gene 80218 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_025146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29533
Approved symbol	NAA50
Name	N-alpha-acetyltransferase 50, NatE catalytic subunit
Location	3q13.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13194, NAT5, San
Ensembl gene	ENSG00000121579
Ensembl biotype	protein_coding
OMIM	610834
Entrez	80218

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000240922, ENST00000467022, ENST00000477813, ENST00000478020, ENST00000481432, ENST00000493454, ENST00000493900, ENST00000497255, ENST00000497525, ENST00000630058, ENST00000881592

RefSeq mRNA: 2 — MANE Select: NM_025146 NM_001308445, NM_025146

CCDS: CCDS2975, CCDS77791

Canonical transcript exons

ENST00000240922 — 5 exons

Exon	Start	End
ENSE00001380209	113716458	113721937
ENSE00003470855	113723959	113724095
ENSE00003559655	113745942	113746249
ENSE00003621166	113723422	113723541
ENSE00003670764	113722906	113722972

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.9127 / max 221.2205, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43855	24.8129	1809
43853	17.4825	1798
43854	2.5890	1383
43852	1.0283	625

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.33	gold quality
biceps brachii	UBERON:0001507	99.06	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.06	gold quality
esophagus squamous epithelium	UBERON:0006920	99.00	gold quality
epithelium of nasopharynx	UBERON:0001951	98.95	gold quality
nasopharynx	UBERON:0001728	98.93	gold quality
germinal epithelium of ovary	UBERON:0001304	98.78	gold quality
palpebral conjunctiva	UBERON:0001812	98.67	gold quality
vastus lateralis	UBERON:0001379	98.60	gold quality
oral cavity	UBERON:0000167	98.45	gold quality
gastrocnemius	UBERON:0001388	98.22	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.15	gold quality
muscle of leg	UBERON:0001383	98.14	gold quality
penis	UBERON:0000989	98.13	gold quality
skeletal muscle tissue	UBERON:0001134	98.12	gold quality
gingival epithelium	UBERON:0001949	98.08	gold quality
epithelium of esophagus	UBERON:0001976	98.08	gold quality
trabecular bone tissue	UBERON:0002483	98.05	gold quality
muscle organ	UBERON:0001630	98.03	gold quality
skeletal muscle organ	UBERON:0014892	98.03	gold quality
gingiva	UBERON:0001828	98.01	gold quality
eye	UBERON:0000970	97.97	gold quality
superficial temporal artery	UBERON:0001614	97.89	gold quality
diaphragm	UBERON:0001103	97.85	gold quality
tibialis anterior	UBERON:0001385	97.74	gold quality
body of tongue	UBERON:0011876	97.74	gold quality
colonic mucosa	UBERON:0000317	97.72	gold quality
parietal pleura	UBERON:0002400	97.72	gold quality
tongue	UBERON:0001723	97.66	gold quality
superior surface of tongue	UBERON:0007371	97.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

309 targeting NAA50, 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-5193	100.00	67.26	1744
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
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-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-373-5P	99.98	75.36	4753

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• The first description of the human homologue of Nat5p/San, hNAT5, the third component of the human NatA N-alpha-acetyltransferase complex (PMID:16507339)
• May be specifically required for the maintenance of centromeric cohesion in mitosis. (PMID:17502424)
• Data show that with MAK3 knockdown, p53 is stabilized and phosphorylated and there is a significant transcriptional activation of proapoptotic genes downstream of p53, and that localization of Arl8b is altered, suggesting that Arl8b is a Mak3 substrate. (PMID:19398576)
• Nat5 displays both protein N alpha- and N epsilon-acetyltransferase activity. (PMID:19744929)
• Naa50p can accommodate only an alpha-amino substrate and not a side chain lysine substrate that is acetylated by lysine acetyltransferase enzymes such as Gcn5. (PMID:21900231)
• Human protein N-terminal acetyltransferase hNaa50p (hNAT5/hSAN) follows ordered sequential catalytic mechanism: combined kinetic and NMR study. (PMID:22311970)
• Development of the first N-terminal acetyltransferase (NAT) inhibitors, including a specific Naa50 inhibitor. (PMID:23557624)
• The study quantitatively compared the Nt-acetylomes of wild-type yeast S. cerevisiae expressing the endogenous yeast Naa50 (yNaa50), the congenic strain lacking yNaa50, and an otherwise identical strain expressing human Naa50 (hNaa50). (PMID:25886145)
• co-depletion of NatA, a heterodimeric NAT complex that physically interacts with Naa50, rescues the sister-chromatid cohesion defects and the resulting mitotic arrest caused by Naa50 depletion, indicating that NatA and Naa50 play antagonistic roles in cohesion. (PMID:27422821)
• Because Naa10 is reported to acetylate all amino termini that are devoid of methionine and Naa50 acetylates all other peptides that are followed by methionine (PMID:27484799)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	naa50	ENSDARG00000027825
mus_musculus	Naa50	ENSMUSG00000022698
rattus_norvegicus	Naa50	ENSRNOG00000039017
drosophila_melanogaster	san	FBGN0024188
caenorhabditis_elegans		WBGENE00018238

Paralogs (4): NAA10 (ENSG00000102030), NAA30 (ENSG00000139977), NAA11 (ENSG00000156269), NAA20 (ENSG00000173418)

Protein

Protein identifiers

N-alpha-acetyltransferase 50 — Q9GZZ1 (reviewed: Q9GZZ1)

Alternative names: N-acetyltransferase 13, N-acetyltransferase 5, N-acetyltransferase san homolog, N-epsilon-acetyltransferase 50, NatE catalytic subunit

All UniProt accessions (8): A0A0D9SF32, B0AZT5, C9J5D1, C9J5J3, C9JZU6, E7EQ69, F8WCK0, Q9GZZ1

UniProt curated annotations — full annotation on UniProt →

Function. N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine. Has a broad substrate specificity: able to acetylate the initiator methionine of most peptides, except for those with a proline in second position. Also displays N-epsilon-acetyltransferase activity by mediating acetylation of the side chain of specific lysines on proteins. Autoacetylates in vivo. The relevance of N-epsilon-acetyltransferase activity is however unclear: able to acetylate H4 in vitro, but this result has not been confirmed in vivo. Component of N-alpha-acetyltransferase complexes containing NAA10 and NAA15, which has N-alpha-acetyltransferase activity. Does not influence the acetyltransferase activity of NAA10. However, it negatively regulates the N-alpha-acetyltransferase activity of the N-terminal acetyltransferase A complex (also called the NatA complex). The multiprotein complexes probably constitute the major contributor for N-terminal acetylation at the ribosome exit tunnel, with NAA10 acetylating all amino termini that are devoid of methionine and NAA50 acetylating other peptides. Required for sister chromatid cohesion during mitosis by promoting binding of CDCA5/sororin to cohesin: may act by counteracting the function of NAA10.

Subunit / interactions. Component of the N-terminal acetyltransferase E (NatE) complex at least composed of NAA10, NAA15 and NAA50. Interacts with NAA10. Interacts with NAA15. Predominantly interacts with NAA15 in the N-terminal acetyltransferase A complex (NatA complex); the interactions reduce the acetylation activity of the NatA complex. Component of the N-terminal acetyltransferase E (NatE)/HYPK complex at least composed of NAA10, NAA15, NAA50 and HYPK. Within the complex interacts with NAA15. Its capacity to interact with the NatA complex is reduced by HYPK. Interacts with NAA35.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the acetyltransferase family. GNAT subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZZ1-1	1	yes
Q9GZZ1-2	2

RefSeq proteins (2): NP_001295374, NP_079422* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR051556	N-term/lysine_N-AcTrnsfr	Family

Pfam: PF00583

Enzyme classification (BRENDA):

• EC 2.3.1.258 — N-terminal methionine Nalpha-acetyltransferase NatE (BRENDA: 8 organisms, 79 substrates, 9 inhibitors, 25 Km, 15 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MVNALE	0.0153–0.1469	6
ACETYL-COA	0.005–0.0069	2
N-TERMINAL-L-METHIONYL-L-LEUCYL-GLYCYL-L-PROLINE	0.0962–0.8315	2
MASS	0.2019	1
MFGPERRR	3.734	1
MIGPERRR	0.185	1
MLALIRRR	0.19	1
MLDPERRR	0.091	1
MLGPERRR	0.079	1
MLGTERRR	0.416	1
MLGTGRRR	0.32	1
MLLPERRR	0.478	1
MLRPERRR	0.46	1

Catalyzed reactions (Rhea), 8 shown:

• N-terminal L-methionyl-L-leucyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-leucyl-[protein] + CoA + H(+) (RHEA:50520)
• N-terminal L-methionyl-L-phenylalanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-phenylalanyl-[protein] + CoA + H(+) (RHEA:50528)
• N-terminal L-methionyl-L-tyrosyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-tyrosyl-[protein] + CoA + H(+) (RHEA:50532)
• N-terminal L-methionyl-L-alanyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-alanyl-[protein] + CoA + H(+) (RHEA:50564)
• N-terminal L-methionyl-L-seryl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-seryl-[protein] + CoA + H(+) (RHEA:50568)
• N-terminal L-methionyl-L-valyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-valyl-[protein] + CoA + H(+) (RHEA:50572)
• N-terminal L-methionyl-L-threonyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-threonyl-[protein] + CoA + H(+) (RHEA:50576)
• N-terminal L-methionyl-L-lysyl-[protein] + acetyl-CoA = N-terminal N(alpha)-acetyl-L-methionyl-L-lysyl-[protein] + CoA + H(+) (RHEA:50580)

UniProt features (52 total): mutagenesis site 17, strand 10, helix 7, modified residue 6, binding site 5, active site 2, turn 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
6WFN	X-RAY DIFFRACTION	1.07
2OB0	X-RAY DIFFRACTION	1.8
6WFO	X-RAY DIFFRACTION	1.85
6WFK	X-RAY DIFFRACTION	1.87
6WF5	X-RAY DIFFRACTION	2.04
2PSW	X-RAY DIFFRACTION	2.1
6WFG	X-RAY DIFFRACTION	2.16
6WF3	X-RAY DIFFRACTION	2.29
4X5K	X-RAY DIFFRACTION	2.49
3TFY	X-RAY DIFFRACTION	2.75
9F1B	ELECTRON MICROSCOPY	3.01
6PPL	ELECTRON MICROSCOPY	3.02
9F1D	ELECTRON MICROSCOPY	3.26
9F1C	ELECTRON MICROSCOPY	3.78
6PW9	ELECTRON MICROSCOPY	4.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZZ1-F1	92.62	0.90

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 (2): 73; 112

Ligand- & substrate-binding residues (5): 31; 75; 77–90; 117–126; 138–141

Post-translational modifications (6): 34, 37, 110, 140, 34, 12

Mutagenesis-validated functional residues (17):

Position	Phenotype
7	restores the acetylation activity of the nata complex.
27	abolishes n-alpha-acetyltransferase activity.
28	strongly decreased n-alpha-acetyltransferase activity.
29	strongly decreased n-alpha-acetyltransferase activity.
31	abolishes n-alpha-acetyltransferase activity.
34–37	decreased acetylation; when associated with a-140.
35	abolishes n-alpha-acetyltransferase activity.
53	restores the acetylation activity of the nata complex.
73	abolishes n-alpha-acetyltransferase activity.
75	reduces n-alpha-acetyltransferase activity.
84	strongly decreased n-alpha-acetyltransferase activity.
112	abolishes n-alpha-acetyltransferase activity.
124	strongly decreased n-alpha-acetyltransferase activity. impaired sister chromatid cohesion during mitosis.
138	abolishes n-alpha-acetyltransferase activity.
139	abolishes n-alpha-acetyltransferase activity.
140	decreased acetylation; when associated with 34-a-a-37.
142	reduces n-alpha-acetyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 286 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GCACCTT_MIR18A_MIR18B, GOBP_CHROMOSOME_ORGANIZATION, GOBP_N_TERMINAL_PROTEIN_AMINO_ACID_ACETYLATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, RORA1_01, TGCACTT_MIR519C_MIR519B_MIR519A, TGACCTY_ERR1_Q2, CTATGCA_MIR153, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, CCATCCA_MIR432, GOBP_PROTEIN_MATURATION, CATTTCA_MIR203

GO Biological Process (6): N-terminal protein amino acid acetylation (GO:0006474), mitotic sister chromatid cohesion (GO:0007064), establishment of mitotic sister chromatid cohesion (GO:0034087), post-translational protein modification (GO:0043687), mitotic sister chromatid cohesion, centromeric (GO:0071962), chromatin remodeling (GO:0006338)

GO Molecular Function (8): protein-N-terminal amino-acid acetyltransferase activity (GO:0004596), histone H4 acetyltransferase activity (GO:0010485), protein-lysine-acetyltransferase activity (GO:0061733), protein N-terminal-methionine acetyltransferase activity (GO:0120518), 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 (6): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), NatA complex (GO:0031415), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic sister chromatid cohesion	2
protein N-acetyltransferase activity	2
cellular anatomical structure	2
protein acetylation	1
N-terminal protein amino acid modification	1
protein maturation	1
sister chromatid cohesion	1
mitotic cell cycle	1
establishment of sister chromatid cohesion	1
mitotic cell cycle process	1
protein modification process	1
centromeric sister chromatid cohesion	1
chromatin organization	1
histone acetyltransferase activity	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
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
N-terminal protein acetyltransferase complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

1986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAA50	NAA15	Q9BXJ9	999
NAA50	NAA10	P41227	981
NAA50	HYPK	Q9NX55	976
NAA50	NAA40	Q86UY6	907
NAA50	NAA60	Q9H7X0	876
NAA50	NAA20	P61599	846
NAA50	NAA25	Q14CX7	718
NAA50	NAA16	Q6N069	717
NAA50	NAA11	Q9BSU3	714
NAA50	NAA35	Q5VZE5	707
NAA50	NAA38	Q9BRA0	594
NAA50	GLYATL1	Q969I3	582
NAA50	NAA80	Q93015	574
NAA50	C1orf105	O95561	536
NAA50	NAA30	Q147X3	519

IntAct

101 interactions, top by confidence:

A	B	Type	Score
NAA15	NAA10	psi-mi:“MI:0914”(association)	0.840
NAA50	NAA15	psi-mi:“MI:0915”(physical association)	0.770
NAA10	NAA50	psi-mi:“MI:0915”(physical association)	0.770
NAA50	NAA10	psi-mi:“MI:0914”(association)	0.770
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
BHLHE40	NAA50	psi-mi:“MI:0915”(physical association)	0.720
JMJD6	NAA50	psi-mi:“MI:0915”(physical association)	0.720
NAA50	BHLHE40	psi-mi:“MI:0915”(physical association)	0.720
NAA50	JMJD6	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NAA10	NAA16	psi-mi:“MI:0914”(association)	0.710
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
HYPK	NAA10	psi-mi:“MI:0914”(association)	0.640
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
NAA50	NAA16	psi-mi:“MI:0915”(physical association)	0.620
OTX2	NAA50	psi-mi:“MI:0915”(physical association)	0.560
Naa50	NAA10	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
RNF26	NME2P1	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
MOK	H1-3	psi-mi:“MI:0914”(association)	0.530

BioGRID (153): NAA50 (Two-hybrid), NAA50 (Two-hybrid), NAA50 (Affinity Capture-MS), NAA50 (Affinity Capture-MS), NAA50 (Affinity Capture-MS), NAA50 (Affinity Capture-MS), NAA50 (Affinity Capture-MS), NAA50 (Affinity Capture-MS), DNAJC7 (Co-fractionation), HNRNPD (Co-fractionation), HNRNPDL (Co-fractionation), NAA50 (Co-fractionation), NAA50 (Co-fractionation), NAA50 (Co-fractionation), NAA50 (Co-fractionation)

ESM2 similar proteins: A0A7U2QYM2, E9RBG1, G0SEV9, O14023, O61219, O94449, P05131, P05383, P22694, P27120, P36416, P48729, P49071, P53034, P53041, P53042, P67827, P67828, P67829, P67962, P67963, P68180, P68181, P68182, P97633, Q02908, Q0G819, Q0IIJ0, Q1ZXC6, Q23651, Q5RF28, Q5TNH5, Q5XGA9, Q60676, Q60LW7, Q6DBY2, Q6GP53, Q6PGB6, Q7XRX1, Q8BK63

Diamond homologs: O74519, Q08689, Q0IIJ0, Q5RF28, Q5XGA9, Q6DBY2, Q6GP53, Q6PGB6, Q9GZZ1, Q9NHD5, O74311, O80438, P07347, P37506, Q03503, Q0IHH1, Q147X3, Q54MP9, Q58604, Q58925, Q8CES0, Q8N9F0, Q95RC0, Q976C3, Q980R9, Q9FKI4, Q9P6R8, Q9UHE5, P0A944, P0A945, P0A946, P0A947, Q8ZJW4, P46854, Q4JBG0, O15541, O17917, P0CQ64, P0CQ65, P53769

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
3:113721933:CATGC:C	acceptor_gain	1.0000
3:113721934:ATGC:A	acceptor_gain	1.0000
3:113721935:TGC:T	acceptor_gain	1.0000
3:113721936:GC:G	acceptor_gain	1.0000
3:113721937:CC:C	acceptor_gain	1.0000
3:113721938:C:CA	acceptor_loss	1.0000
3:113721938:C:CC	acceptor_gain	1.0000
3:113721943:A:AC	acceptor_gain	1.0000
3:113721943:A:C	acceptor_gain	1.0000
3:113721945:A:AC	acceptor_gain	1.0000
3:113721945:A:C	acceptor_gain	1.0000
3:113721957:C:CT	acceptor_gain	1.0000
3:113721958:A:T	acceptor_gain	1.0000
3:113722897:TTTAC:T	donor_loss	1.0000
3:113722898:TTACT:T	donor_loss	1.0000
3:113722899:TAC:T	donor_loss	1.0000
3:113722900:AC:A	donor_loss	1.0000
3:113722901:C:CG	donor_loss	1.0000
3:113722902:TT:T	donor_loss	1.0000
3:113722903:TACA:T	donor_loss	1.0000
3:113722904:A:AC	donor_gain	1.0000
3:113722904:A:C	donor_loss	1.0000
3:113722905:C:CA	donor_gain	1.0000
3:113723424:ATT:A	donor_gain	1.0000
3:113723956:TACCA:T	donor_loss	1.0000
3:113723982:T:TA	donor_gain	1.0000
3:113723991:T:TA	donor_gain	1.0000
3:113724093:CTA:C	acceptor_gain	1.0000
3:113724094:TA:T	acceptor_gain	1.0000
3:113724096:C:CC	acceptor_gain	1.0000

AlphaMissense

1125 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:113721821:A:G	L150P	1.000
3:113721830:G:T	A147D	1.000
3:113721831:C:G	A147P	1.000
3:113721855:A:G	Y139H	1.000
3:113721883:A:C	F129L	1.000
3:113721883:A:T	F129L	1.000
3:113721884:A:G	F129S	1.000
3:113721885:A:G	F129L	1.000
3:113721902:A:G	F123S	1.000
3:113721932:A:T	V113D	1.000
3:113721934:A:C	H112Q	1.000
3:113721934:A:T	H112Q	1.000
3:113721935:T:C	H112R	1.000
3:113722906:A:G	L111P	1.000
3:113722906:A:T	L111Q	1.000
3:113722951:A:T	V96D	1.000
3:113722963:A:C	M92R	1.000
3:113722972:C:A	G89V	1.000
3:113722972:C:T	G89E	1.000
3:113723422:C:G	G89R	1.000
3:113723422:C:T	G89R	1.000
3:113723436:C:G	R84P	1.000
3:113723448:A:G	L80P	1.000
3:113723450:A:C	C79W	1.000
3:113723452:A:G	C79R	1.000
3:113723454:C:T	G78E	1.000
3:113723455:C:G	G78R	1.000
3:113723455:C:T	G78R	1.000
3:113723457:A:G	L77P	1.000
3:113723466:A:T	I74N	1.000

dbSNP variants (sampled 300 via entrez): RS1000032316 (3:113728338 C>G), RS1000358130 (3:113747010 G>A,C,T), RS1000377431 (3:113738939 A>G), RS1000519760 (3:113732871 T>C,G), RS1000589373 (3:113743053 G>A), RS1000635767 (3:113730361 A>G,T), RS1000687900 (3:113730604 A>G), RS1000688367 (3:113738725 T>A), RS1000785487 (3:113717529 G>A), RS1000842168 (3:113724620 A>G), RS1001105675 (3:113718092 GCTCA>G), RS1001296507 (3:113718710 T>C), RS1001315355 (3:113724775 C>T), RS1001591057 (3:113741745 A>T), RS1001602256 (3:113718308 G>A,C)

Disease associations

OMIM: gene MIM:610834 | 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
GCST001942_7	Prostate cancer	4.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630854 (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: 10,084 (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
CHEMBL1213327	COENZYME_A	3	10,084

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

ChEMBL bioactivities

24 potent at pChembl≥5 of 28 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	CHEMBL4645901
7.89	IC50	13	nM	CHEMBL4642788
7.89	IC50	13	nM	CHEMBL4642700
7.85	IC50	14	nM	CHEMBL4639216
7.75	Kd	17.6	nM	CHEMBL1230809
7.57	Kd	26.7	nM	CHEMBL4645901
7.52	IC50	30	nM	CHEMBL4642911
7.50	Kd	32	nM	CHEMBL4645901
7.06	IC50	88	nM	CHEMBL4644527
6.98	Kd	105	nM	CHEMBL4645901
6.81	Kd	156	nM	COENZYME_A
6.77	IC50	170	nM	CHEMBL4636177
6.37	IC50	430	nM	CHEMBL4648534
6.33	Kd	470	nM	CHEMBL4645967
6.33	Kd	471	nM	CHEMBL4645967
6.00	IC50	1000	nM	CHEMBL4640907
6.00	Kd	1010	nM	CHEMBL4635926
5.80	IC50	1600	nM	CHEMBL4645967
5.76	Kd	1749	nM	CHEMBL5653589
5.76	ED50	1749	nM	CHEMBL5653589
5.70	IC50	2000	nM	CHEMBL4635926
5.57	IC50	2700	nM	CHEMBL4635301
5.54	IC50	2900	nM	CHEMBL4636574
5.41	IC50	3900	nM	CHEMBL4632414

PubChem BioAssay actives

23 with measured affinity, of 59 total; 17 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
N-methyl-2-[(2S,4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-1-[4-(2H-tetrazol-5-yl)benzoyl]pyrrolidin-2-yl]-1,3-thiazole-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.0070	uM
N-methyl-2-[(4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-1-[4-(2H-tetrazol-5-yl)benzoyl]pyrrolidin-2-yl]-1,3-thiazole-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.0130	uM
(4S)-1-methyl-N-[(3S,5S)-5-(4-methyl-1,3-thiazol-2-yl)-1-[4-(2H-tetrazol-5-yl)benzoyl]pyrrolidin-3-yl]-2,6-dioxo-1,3-diazinane-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.0130	uM
N-methyl-2-[(2S,4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-1-[4-(2H-tetrazol-5-yl)benzoyl]pyrrolidin-2-yl]-1,3-oxazole-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.0140	uM
S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] ethanethioate	1658396: Binding affinity to full length human N-terminal His-tagged/GST-tagged Naa50 expressed in Escherichia coli BL21(DE3) cells in by SPR analysis	kd	0.0176	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-4-[[3-[2-[2-[[(2S)-1-[[(2S)-1-[[2-[(2S)-2-carbamoylpyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.0300	uM
N-methyl-2-[(2S,4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-1-[[4-(2H-tetrazol-5-yl)phenyl]methyl]pyrrolidin-2-yl]-1,3-thiazole-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.0880	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-[[3-oxo-3-(2-sulfanylethylamino)propyl]amino]butyl] hydrogen phosphate	1658396: Binding affinity to full length human N-terminal His-tagged/GST-tagged Naa50 expressed in Escherichia coli BL21(DE3) cells in by SPR analysis	kd	0.1560	uM
4-[(2S,4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-2-(4-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carbonyl]benzoic acid	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.1700	uM
N-methyl-2-[(2S,4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-1-[3-(2H-tetrazol-5-yl)benzoyl]pyrrolidin-2-yl]-1,3-thiazole-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	0.4300	uM
N-methyl-2-[(2R,4S)-4-[[(4S)-1-methyl-2,6-dioxo-1,3-diazinane-4-carbonyl]amino]-1-[4-(2H-tetrazol-5-yl)benzoyl]pyrrolidin-2-yl]-1,3-thiazole-4-carboxamide	1658384: Binding affinity to full length human N-terminal His-tagged/GST-tagged Naa50 expressed in Escherichia coli BL21(DE3) cells in presence of acetyl CoA by SPR analysis	kd	0.4700	uM
(4S)-1-methyl-N-[(3S,5S)-5-(4-methyl-1,3-thiazol-2-yl)-1-[4-(1H-1,2,4-triazol-5-yl)benzoyl]pyrrolidin-3-yl]-2,6-dioxo-1,3-diazinane-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	1.0000	uM
(2S)-N-[(2S)-3-[1-(3-tert-butyl-1-methylpyrazole-5-carbonyl)piperidin-4-yl]-1-(methylamino)-1-oxopropan-2-yl]-6-oxopiperidine-2-carboxamide	1658384: Binding affinity to full length human N-terminal His-tagged/GST-tagged Naa50 expressed in Escherichia coli BL21(DE3) cells in presence of acetyl CoA by SPR analysis	kd	1.0100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148816: Binding affinity to human NAA50 incubated for 45 mins by Kinobead based pull down assay	kd	1.7489	uM
N-[(2S)-3-[1-(3-tert-butyl-1-methylpyrazole-5-carbonyl)piperidin-4-yl]-1-(methylamino)-1-oxopropan-2-yl]-6-oxopiperidine-2-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	2.7000	uM
(4S)-1-methyl-N-[(3S,5S)-5-(4-methyl-1,3-thiazol-2-yl)-1-[4-(triazol-1-yl)benzoyl]pyrrolidin-3-yl]-2,6-dioxo-1,3-diazinane-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	2.9000	uM
(4S)-1-methyl-N-[(3S,5S)-5-(4-methyl-1,3-thiazol-2-yl)-1-[4-(tetrazol-2-yl)benzoyl]pyrrolidin-3-yl]-2,6-dioxo-1,3-diazinane-4-carboxamide	1658383: Inhibition of wild type human Naa50 (1852 to 2082 residues) expressed in Escherichia coli BL21(DE3) cells using MLGPEGGEGK peptide as substrate after 75 mins in presence of acetyl CoA by rapidfire mass spectrometry analysis	ic50	3.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Demecolcine	decreases expression	1
Dexamethasone	increases expression	1
Drugs, Chinese Herbal	increases expression	1
Environmental Pollutants	affects expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Naphthoquinones	increases expression	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4618906	Binding	Binding affinity to full length human N-terminal His-tagged/GST-tagged Naa50 expressed in Escherichia coli BL21(DE3) cells assessed as change in melting temperature at 250 uM after 15 mins in presence of acetyl-CoA by SYPRO Orange dye based	Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library. — ACS Med Chem Lett

Clinical trials (associated diseases)

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