NAA15

Summary

NAA15 (N-alpha-acetyltransferase 15, NatA auxiliary subunit, HGNC:30782) is a protein-coding gene on chromosome 4q31.1, encoding N-alpha-acetyltransferase 15, NatA auxiliary subunit (Q9BXJ9). Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity. It is a common-essential gene (DepMap: required in 97.4% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes the auxillary subunit of the N-terminal acetyltransferase A (NatA) complex.

Source: NCBI Gene 80155 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 665 total — 90 pathogenic, 65 likely-pathogenic
• Phenotypes (HPO): 10
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_057175

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30782
Approved symbol	NAA15
Name	N-alpha-acetyltransferase 15, NatA auxiliary subunit
Location	4q31.1
Locus type	gene with protein product
Status	Approved
Aliases	TBDN100, NATH, FLJ13340
Ensembl gene	ENSG00000164134
Ensembl biotype	protein_coding
OMIM	608000
Entrez	80155

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000296543, ENST00000398947, ENST00000468029, ENST00000480277, ENST00000482087, ENST00000485905, ENST00000496716, ENST00000515576, ENST00000700275, ENST00000700276, ENST00000700277, ENST00000700278, ENST00000700279, ENST00000700280, ENST00000700281, ENST00000920373, ENST00000920374, ENST00000920375, ENST00000920376

RefSeq mRNA: 2 — MANE Select: NM_057175 NM_001410842, NM_057175

CCDS: CCDS43270, CCDS93635

Canonical transcript exons

ENST00000296543 — 20 exons

Exon	Start	End
ENSE00001081738	139360500	139360628
ENSE00001081743	139384832	139384978
ENSE00001081744	139376365	139376473
ENSE00001081748	139351505	139351611
ENSE00001081752	139370211	139370404
ENSE00001081753	139361724	139361937
ENSE00001081754	139378756	139378854
ENSE00001081755	139359743	139359895
ENSE00001081756	139386133	139386230
ENSE00003518493	139349462	139349581
ENSE00003559814	139357386	139357555
ENSE00003568346	139336848	139336952
ENSE00003579674	139351191	139351286
ENSE00003582672	139344186	139344339
ENSE00003619484	139334174	139334258
ENSE00003651541	139342826	139342960
ENSE00003655540	139354026	139354098
ENSE00003668005	139340912	139341069
ENSE00003979409	139301505	139301831
ENSE00003979416	139387884	139391384

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 92.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.0642 / max 601.6638, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49744	39.0642	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.88	gold quality
adrenal tissue	UBERON:0018303	92.34	gold quality
ventricular zone	UBERON:0003053	91.06	gold quality
cervix squamous epithelium	UBERON:0006922	90.65	silver quality
pericardium	UBERON:0002407	90.61	gold quality
tendon	UBERON:0000043	89.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.90	gold quality
cortical plate	UBERON:0005343	89.78	gold quality
tonsil	UBERON:0002372	89.53	gold quality
biceps brachii	UBERON:0001507	89.50	gold quality
secondary oocyte	CL:0000655	89.32	gold quality
pylorus	UBERON:0001166	89.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.02	gold quality
colonic epithelium	UBERON:0000397	89.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.69	gold quality
ganglionic eminence	UBERON:0004023	88.43	gold quality
body of tongue	UBERON:0011876	88.35	gold quality
corpus callosum	UBERON:0002336	88.04	gold quality
oral cavity	UBERON:0000167	87.59	gold quality
superior surface of tongue	UBERON:0007371	87.22	gold quality
esophagus squamous epithelium	UBERON:0006920	87.03	gold quality
buccal mucosa cell	CL:0002336	87.01	gold quality
pharyngeal mucosa	UBERON:0000355	86.95	gold quality
colonic mucosa	UBERON:0000317	86.83	gold quality
gastrocnemius	UBERON:0001388	86.60	gold quality
squamous epithelium	UBERON:0006914	86.59	gold quality
oocyte	CL:0000023	86.56	gold quality
postcentral gyrus	UBERON:0002581	86.52	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)

348 targeting NAA15, 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-3120-5P	100.00	65.56	965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-186-5P	99.99	70.83	3707
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-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-3692-3P	99.98	70.27	2139

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• NATH, a novel gene overexpressed in papillary thyroid carcinomas. (PMID:12140756)
• Human Naa15 (NATH) and Naa10 (ARD1) form a stable NatA complex which associates with ribosomes and performs co-translational N-terminal acetylation; Naa15 (NATH) and Naa10 (ARD1) are cleaved during apoptosis resulting in decreased acetyltransferase activity (PMID:15496142)
• NATH complexes with hARD1 in a ribosomal associated protein-N-acetyltransferase complex. (PMID:15496142)
• description of the human homologue of Nat1p, NATH (NAT human), as the binding partner of the hARD1 (human ARD1) protein (PMID:15496142)
• levels of endogenous NATH and hARD1 proteins in thyroid papillary carcinoma patients; results suggest that NATH positively affects the level of hARD1 protein both in vivo and in cell cultures (PMID:16279846)
• Loss of retinal endothelial Tbdn-1 expression may be a contributing factor in retinal blood vessel proliferation in retinopathy of prematurity. (PMID:16518308)
• Essential role in cell survival through protein N-alpha-acetylation. (PMID:16518407)
• Data indicate that the physical interaction between HYPK and NatA Naa10/15 seems to be of functional importance both for huntingtin aggregation and for N-terminal acetylation. (PMID:20154145)
• Protein N-terminal acetyltransferases (NATs), including the NatA complex composed of Naa10 (ARD1) and Naa15 (NATH), act as N-terminal propionyltransferases. (PMID:23043182)
• Development of the first N-terminal acetyltransferase (NAT) inhibitors, including inhibitors to the NatA complex composed of Naa10 (ARD1) and Naa15 (NATH). (PMID:23557624)
• In combination with acetylation assays, the HypK N-terminal region is identified as a negative regulator of the NatA acetylation activity (PMID:28585574)
• Authors highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain. (PMID:28990276)
• individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. (PMID:29656860)
• Results provide evidence that Naa15 metazoan-specific domain contributes to N-terminal acetyltransferases A activity and stability. (PMID:29754825)
• Structure and mechanism of acetylation by the N-terminal dual enzyme NatA/Naa50 complex has been reported. (PMID:31155310)
• Variants in NAA15 cause pediatric hypertrophic cardiomyopathy. (PMID:33103328)
• Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency. (PMID:33557580)
• Possible Catch-Up Developmental Trajectories for Children with Mild Developmental Delay Caused by NAA15 Pathogenic Variants. (PMID:35328089)
• Expanding the phenotypic spectrum of NAA10-related neurodevelopmental syndrome and NAA15-related neurodevelopmental syndrome. (PMID:37130971)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	naa15a	ENSDARG00000003213
danio_rerio	naa15b	ENSDARG00000030368
mus_musculus	Naa15	ENSMUSG00000063273
rattus_norvegicus	Naa15	ENSRNOG00000012385
drosophila_melanogaster	Naa15-16	FBGN0031020
caenorhabditis_elegans		WBGENE00021754

Paralogs (2): NAA25 (ENSG00000111300), NAA16 (ENSG00000172766)

Protein

Protein identifiers

N-alpha-acetyltransferase 15, NatA auxiliary subunit — Q9BXJ9 (reviewed: Q9BXJ9)

Alternative names: Gastric cancer antigen Ga19, N-terminal acetyltransferase, NMDA receptor-regulated protein 1, Protein tubedown-1, Tbdn100

All UniProt accessions (8): A0A0B4J1W3, A0A8V8TPI7, A0A8V8TQ00, A0A8V8TQ34, A0A8V8TQT7, A0A8V8TR41, D6RAP7, Q9BXJ9

UniProt curated annotations — full annotation on UniProt →

Function. Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity. The NAT activity may be important for vascular, hematopoietic and neuronal growth and development. Required to control retinal neovascularization in adult ocular endothelial cells. In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter.

Subunit / interactions. Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15. Within the complex interacts with NAA10. Component of the N-terminal acetyltransferase A (NatA)/HYPK complex at least composed of NAA10, NAA15 and HYPK, which has N-terminal acetyltransferase activity. In complex with NAA10, interacts with HYPK. Component of the N-terminal acetyltransferase E (NatE) complex at least composed of NAA10, NAA15 and NAA50. Within the complex interacts with NAA10; the interaction is required for binding to NAA50. Interacts with NAAT50. The interaction of the NatA complex with NAA50 reduces 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. In complex with NAA10 interacts with HYPK; the interaction with HYPK reduces the capacity of the NatA complex to interact with NAA50. Interacts with NAA11. Interacts with XRCC6 and XRCC5.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed at high levels in testis and in ocular endothelial cells. Also found in brain (corpus callosum), heart, colon, bone marrow and at lower levels in most adult tissues, including thyroid, liver, pancreas, mammary and salivary glands, lung, ovary, urogenital system and upper gastrointestinal tract. Overexpressed in gastric cancer, in papillary thyroid carcinomas and in a Burkitt lymphoma cell line (Daudi). Specifically suppressed in abnormal proliferating blood vessels in eyes of patients with proliferative diabetic retinopathy.

Post-translational modifications. Cleaved by caspases during apoptosis, resulting in a stable 35 kDa fragment.

Disease relevance. Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities (MRD50) [MIM:617787] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BXJ9-1	1, Long	yes
Q9BXJ9-4	2, Short

RefSeq proteins (2): NP_001397771, NP_476516* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR021183	NatA_aux_su	Family

Pfam: PF12569, PF13181

Enzyme classification (BRENDA):

• EC 2.3.1.255 — N-terminal amino-acid Nalpha-acetyltransferase NatA (BRENDA: 13 organisms, 96 substrates, 5 inhibitors, 24 Km, 23 kcat entries)
• 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)

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

Substrate	Km (mM)	Measurements
SASEAGVRWGRPVGRRRRP	0.3–1.85	19
MVNALE	0.0153–0.1469	6
ACETYL-COA	0.196–0.6717	4
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

UniProt features (99 total): helix 51, sequence variant 9, repeat 8, modified residue 8, strand 8, compositionally biased region 3, mutagenesis site 3, region of interest 2, splice variant 2, turn 2, chain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
9FPZ	ELECTRON MICROSCOPY	2.69
6C9M	X-RAY DIFFRACTION	2.8
9F1B	ELECTRON MICROSCOPY	3.01
6PPL	ELECTRON MICROSCOPY	3.02
6C95	X-RAY DIFFRACTION	3.15
9F1D	ELECTRON MICROSCOPY	3.26
9QQB	ELECTRON MICROSCOPY	3.43
9F1C	ELECTRON MICROSCOPY	3.78
9GJ6	ELECTRON MICROSCOPY	3.91
6PW9	ELECTRON MICROSCOPY	4.03
9GJ5	ELECTRON MICROSCOPY	4.61
9FQ0	ELECTRON MICROSCOPY	4.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXJ9-F1	89.66	0.78

Functional residue map

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

Post-translational modifications (8): 262, 302, 537, 588, 735, 756, 855, 856

Mutagenesis-validated functional residues (3):

Position	Phenotype
406	reduces binding to naa50, but increases binding to hypk. reduces catalytic activity of the nata complex while retaining
814	reduces binding to hypk, increases binding to naa50. increases catalytic activity of the nata complex while retaining th
834	reduces nata complex stability and reduces catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 312 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GGTGTGT_MIR329, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, XU_GH1_AUTOCRINE_TARGETS_UP, AMIT_EGF_RESPONSE_60_HELA, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GTGCCTT_MIR506

GO Biological Process (7): angiogenesis (GO:0001525), cell differentiation (GO:0030154), positive regulation of DNA-templated transcription (GO:0045893), protein stabilization (GO:0050821), protein maturation (GO:0051604), N-terminal protein amino acid acetylation (GO:0006474), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (5): RNA binding (GO:0003723), acetyltransferase activator activity (GO:0010698), ribosome binding (GO:0043022), protein binding (GO:0005515), acetyltransferase activity (GO:0016407)

GO Cellular Component (7): nucleus (GO:0005634), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nuclear body (GO:0016604), NatA complex (GO:0031415)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cellular developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of protein stability	1
gene expression	1
protein metabolic process	1
protein acetylation	1
N-terminal protein amino acid modification	1
protein maturation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
nucleic acid binding	1
enzyme activator activity	1
acetyltransferase activity	1
ribonucleoprotein complex binding	1
binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
N-terminal protein acetyltransferase complex	1

Protein interactions and networks

STRING

1672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAA15	NAA50	Q9GZZ1	999
NAA15	NAA10	P41227	999
NAA15	HYPK	Q9NX55	983
NAA15	NAA20	P61599	977
NAA15	ICE2	Q659A1	940
NAA15	NAA25	Q14CX7	931
NAA15	NAA11	Q9BSU3	846
NAA15	NAA40	Q86UY6	796
NAA15	NAA30	Q147X3	794
NAA15	NAA35	Q5VZE5	774
NAA15	NAA60	Q9H7X0	766
NAA15	MNAT1	P51948	762
NAA15	ESCO1	Q5FWF5	729
NAA15	ESCO2	Q56NI9	728
NAA15	NAT1	P18440	714

IntAct

108 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
NAA15	NAA10	psi-mi:“MI:0914”(association)	0.840
NAA15	HYPK	psi-mi:“MI:0915”(physical association)	0.840
NAA10	NAA15	psi-mi:“MI:0915”(physical association)	0.840
NAA10	NAA15	psi-mi:“MI:0403”(colocalization)	0.840
NAA50	NAA15	psi-mi:“MI:0915”(physical association)	0.770
NAA50	NAA10	psi-mi:“MI:0914”(association)	0.770
NAA10	NAA16	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HYPK	NAA10	psi-mi:“MI:0914”(association)	0.640
NAA15	NAA11	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
TRAFD1	ACAD11	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
NAA10	OFD1	psi-mi:“MI:0914”(association)	0.480
	AP3D1	psi-mi:“MI:0914”(association)	0.460
Naa10	NAA10	psi-mi:“MI:0915”(physical association)	0.400
Naa15	NAA10	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (237): NAA15 (Affinity Capture-MS), NAA15 (Affinity Capture-MS), NAA15 (Affinity Capture-MS), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation), NAA15 (Co-fractionation)

ESM2 similar proteins: A0JN39, A8WGF4, B5DGH9, D2SW95, O00232, O60763, O95782, P17426, P23514, P41541, P53618, P91926, P93768, Q05AY2, Q0JNK5, Q1LUA8, Q29N38, Q2KJ25, Q3B8M3, Q3UGF1, Q4R4I8, Q53PC7, Q5R4J9, Q5R664, Q5R922, Q5RBI3, Q5VQ78, Q5XI83, Q5ZIA5, Q5ZLA5, Q66HV4, Q6DRI1, Q6H8D5, Q6H8D6, Q6N069, Q6NWV3, Q6P7L9, Q7QG73, Q80UM3, Q8BWQ6

Diamond homologs: O74985, P12945, Q5R4J9, Q6N069, Q80UM3, Q8VZM1, Q9BXJ9, Q9DBB4, Q9Y7X2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NAA15	“form complex”	NatA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
Signaling by high-kinase activity BRAF mutants	5	19.8×	1e-03
MAP2K and MAPK activation	5	17.8×	1e-03
Signaling by RAF1 mutants	5	17.4×	1e-03
Signaling by moderate kinase activity BRAF mutants	5	15.9×	1e-03
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	15.9×	1e-03
Signaling downstream of RAS mutants	5	15.9×	1e-03
Signaling by BRAF and RAF1 fusions	6	12.8×	1e-03
Loss of Nlp from mitotic centrosomes	5	9.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	90
Likely pathogenic	65
Uncertain significance	294
Likely benign	126
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070402	NM_057175.5(NAA15):c.280A>T (p.Lys94Ter)	Pathogenic
1074822	NM_057175.5(NAA15):c.434del (p.Pro145fs)	Pathogenic
1174541	NM_057175.5(NAA15):c.908-2A>G	Pathogenic
1177057	NM_057175.5(NAA15):c.334G>A (p.Asp112Asn)	Pathogenic
1177059	NM_057175.5(NAA15):c.1450T>C (p.Cys484Arg)	Pathogenic
1177066	NM_057175.5(NAA15):c.2441T>C (p.Leu814Pro)	Pathogenic
1184914	NM_057175.5(NAA15):c.922G>T (p.Glu308Ter)	Pathogenic
1320186	NM_057175.5(NAA15):c.1720dup (p.Thr574fs)	Pathogenic
1326070	NM_057175.5(NAA15):c.692-2_692-1del	Pathogenic
1330221	NM_057175.5(NAA15):c.995T>G (p.Leu332Ter)	Pathogenic
1344906	NM_057175.5(NAA15):c.1624_1627delinsAT (p.Leu542fs)	Pathogenic
1675964	NM_057175.5(NAA15):c.692-2del	Pathogenic
1679219	NM_057175.5(NAA15):c.2320_2332del (p.Tyr774fs)	Pathogenic
1691737	NM_057175.5(NAA15):c.1410+5G>A	Pathogenic
1699231	NM_057175.5(NAA15):c.1051del (p.Thr351fs)	Pathogenic
1700107	NM_057175.5(NAA15):c.1027G>T (p.Glu343Ter)	Pathogenic
1703496	NM_057175.5(NAA15):c.1088-2A>G	Pathogenic
1711596	NM_057175.5(NAA15):c.783C>A (p.Tyr261Ter)	Pathogenic
1802607	NM_057175.5(NAA15):c.1165C>T (p.Gln389Ter)	Pathogenic
1803747	NM_057175.5(NAA15):c.1418_1421dup (p.Ala475fs)	Pathogenic
2010273	NM_057175.5(NAA15):c.1828G>T (p.Glu610Ter)	Pathogenic
2020770	NM_057175.5(NAA15):c.28G>T (p.Glu10Ter)	Pathogenic
2121389	NM_057175.5(NAA15):c.482T>A (p.Leu161Ter)	Pathogenic
2227689	NM_057175.5(NAA15):c.2077C>T (p.Gln693Ter)	Pathogenic
2232084	NM_057175.5(NAA15):c.2298_2299dup (p.Ser767fs)	Pathogenic
2245562	NM_057175.5(NAA15):c.1447C>T (p.Gln483Ter)	Pathogenic
2247415	NM_057175.5(NAA15):c.326G>A (p.Trp109Ter)	Pathogenic
2427165	NC_000004.11:g.(?140255308)(140255432_?)del	Pathogenic
2427166	NC_000004.11:g.(?140263960)(140265513_?)del	Pathogenic
2442380	NM_057175.5(NAA15):c.908-2A>C	Pathogenic

SpliceAI

3567 predictions. Top by Δscore:

Variant	Effect	Δscore
4:139301829:TTGGT:T	donor_loss	1.0000
4:139301830:TGG:T	donor_loss	1.0000
4:139301831:GGT:G	donor_loss	1.0000
4:139301832:G:GA	donor_loss	1.0000
4:139301832:G:GG	donor_gain	1.0000
4:139334173:GAGGT:G	acceptor_gain	1.0000
4:139334257:AGG:A	donor_loss	1.0000
4:139334258:GGT:G	donor_loss	1.0000
4:139334259:GTA:G	donor_loss	1.0000
4:139334260:TAAG:T	donor_loss	1.0000
4:139336839:T:TA	acceptor_gain	1.0000
4:139336895:G:GT	donor_gain	1.0000
4:139336944:GTCAT:G	donor_gain	1.0000
4:139342822:A:AG	acceptor_gain	1.0000
4:139342822:AAAG:A	acceptor_gain	1.0000
4:139342823:A:G	acceptor_gain	1.0000
4:139342956:AACAG:A	donor_loss	1.0000
4:139342957:ACAGG:A	donor_loss	1.0000
4:139342958:CAG:C	donor_loss	1.0000
4:139342959:AGG:A	donor_loss	1.0000
4:139342960:GG:G	donor_loss	1.0000
4:139342961:G:A	donor_loss	1.0000
4:139342962:T:A	donor_loss	1.0000
4:139344182:ACAGA:A	acceptor_loss	1.0000
4:139344183:C:G	acceptor_gain	1.0000
4:139344183:CAGAC:C	acceptor_loss	1.0000
4:139344184:A:AC	acceptor_loss	1.0000
4:139344184:A:AG	acceptor_gain	1.0000
4:139344185:G:GA	acceptor_gain	1.0000
4:139344185:G:GT	acceptor_loss	1.0000

AlphaMissense

5759 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:139334183:G:A	E22K	1.000
4:139334190:A:T	K24I	1.000
4:139334191:A:C	K24N	1.000
4:139334191:A:T	K24N	1.000
4:139334204:G:A	G29R	1.000
4:139334204:G:C	G29R	1.000
4:139334205:G:A	G29E	1.000
4:139334226:T:A	I36K	1.000
4:139334226:T:G	I36R	1.000
4:139334256:G:A	G46E	1.000
4:139336856:G:C	A50P	1.000
4:139336857:C:A	A50D	1.000
4:139336860:T:A	M51K	1.000
4:139336860:T:G	M51R	1.000
4:139336865:G:A	G53R	1.000
4:139336865:G:C	G53R	1.000
4:139336866:G:A	G53E	1.000
4:139336866:G:T	G53V	1.000
4:139336869:T:C	L54S	1.000
4:139336914:T:A	V69D	1.000
4:139336922:G:C	G72R	1.000
4:139336923:G:A	G72D	1.000
4:139336926:T:C	L73S	1.000
4:139336926:T:G	L73W	1.000
4:139336943:A:C	S79R	1.000
4:139336945:T:A	S79R	1.000
4:139336945:T:G	S79R	1.000
4:139336952:T:C	C82R	1.000
4:139340912:G:A	C82Y	1.000
4:139340913:T:G	C82W	1.000

dbSNP variants (sampled 300 via entrez): RS1000048521 (4:139340284 G>A,C), RS1000071133 (4:139343694 C>G), RS1000099006 (4:139333621 T>C), RS1000124112 (4:139304103 A>G), RS1000138983 (4:139372041 A>G), RS1000178423 (4:139317361 C>T), RS1000186300 (4:139321631 C>A), RS1000224331 (4:139366507 A>G), RS1000249720 (4:139363338 C>T), RS1000277883 (4:139349158 G>C), RS1000293026 (4:139317484 G>C), RS1000373298 (4:139306400 T>G), RS1000410436 (4:139302930 T>C), RS1000449463 (4:139301439 A>G), RS10004992 (4:139358165 A>C)

Disease associations

OMIM: gene MIM:608000 | disease phenotypes: MIM:617787, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 50	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (6): intellectual disability, autosomal dominant 50 (MONDO:0030916), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), autism (MONDO:0005260), autism spectrum disorder (MONDO:0005258), syndromic intellectual disability (MONDO:0000508)

Orphanet (3): Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

10 total (11 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0007018	Attention deficit hyperactivity disorder
HP:0011968	Feeding difficulties
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067401 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.68	Kd	2069	nM	CHEMBL5653589
5.68	ED50	2069	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148815: Binding affinity to human NAA15 incubated for 45 mins by Kinobead based pull down assay	kd	2.0688	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases activity, increases expression	3
Estradiol	increases expression	2
Nickel	increases expression	2
Quercetin	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	increases expression, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Atrazine	decreases expression	1
Cisplatin	decreases expression, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651857	Binding	Binding affinity to human NAA15 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study