NOA1

Summary

NOA1 (nitric oxide associated 1, HGNC:28473) is a protein-coding gene on chromosome 4q12, encoding Nitric oxide-associated protein 1 (Q8NC60). Involved in regulation of mitochondrial protein translation and respiration. It is a selective cancer dependency (DepMap: 19.5% of cell lines).

The protein encoded by this gene is a nuclear-encoded GTPase that functions in the mitochondrion. Upon translation, this protein is imported into the nucleus and then into the nucleolus before being exported to the mitochondrion. The encoded protein is required for oxygen-dependent regulation of mitochondrial respiratory complexes and for mitochondrial protein synthesis.

Source: NCBI Gene 84273 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 124 total
• Cancer dependency (DepMap): dependent in 19.5% of screened cell lines
• MANE Select transcript: NM_032313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28473
Approved symbol	NOA1
Name	nitric oxide associated 1
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	MGC3232, hAtNOS1, hNOA1, MTG3
Ensembl gene	ENSG00000084092
Ensembl biotype	protein_coding
OMIM	614919
Entrez	84273

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000264230, ENST00000904429, ENST00000904430, ENST00000904431, ENST00000904432, ENST00000904433, ENST00000933297

RefSeq mRNA: 1 — MANE Select: NM_032313 NM_032313

CCDS: CCDS3510

Canonical transcript exons

ENST00000264230 — 7 exons

Exon	Start	End
ENSE00001032846	56973148	56973353
ENSE00001032848	56973858	56974022
ENSE00001032858	56964406	56964526
ENSE00001074715	56966620	56966736
ENSE00001074718	56968384	56968515
ENSE00001074719	56976442	56977606
ENSE00001074722	56963350	56963661

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 95.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7500 / max 161.5346, expressed in 1810 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52229	24.3554	1807
52227	2.4845	1394
52228	1.0804	706
52230	0.8297	612

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	95.32	silver quality
ileal mucosa	UBERON:0000331	93.92	gold quality
upper leg skin	UBERON:0004262	92.41	gold quality
upper arm skin	UBERON:0004263	92.40	gold quality
bronchial epithelial cell	CL:0002328	90.02	gold quality
body of pancreas	UBERON:0001150	89.90	gold quality
cortical plate	UBERON:0005343	89.56	gold quality
deltoid	UBERON:0001476	89.54	silver quality
parotid gland	UBERON:0001831	89.50	gold quality
gastrocnemius	UBERON:0001388	89.49	gold quality
bronchus	UBERON:0002185	89.48	gold quality
muscle of leg	UBERON:0001383	89.03	gold quality
jejunal mucosa	UBERON:0000399	88.98	gold quality
skin of hip	UBERON:0001554	88.49	gold quality
quadriceps femoris	UBERON:0001377	88.38	gold quality
oral cavity	UBERON:0000167	87.84	gold quality
tibia	UBERON:0000979	87.76	gold quality
biceps brachii	UBERON:0001507	87.63	gold quality
pancreas	UBERON:0001264	87.60	gold quality
duodenum	UBERON:0002114	87.58	gold quality
monocyte	CL:0000576	87.55	gold quality
leukocyte	CL:0000738	87.53	gold quality
mammalian vulva	UBERON:0000997	87.48	gold quality
vastus lateralis	UBERON:0001379	87.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.35	gold quality
parietal pleura	UBERON:0002400	86.98	gold quality
oviduct epithelium	UBERON:0004804	86.78	gold quality
secondary oocyte	CL:0000655	86.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.55	gold quality
embryo	UBERON:0000922	86.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NOA1, 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-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-555	95.92	65.25	564
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 19.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• The present study suggests a novel function for mAtNOS1 in regulating mitochondrial nitric oxide and calcium and inducing apoptosis of MCF-7 cells (PMID:18456285)
• This study indicates rhat C4orf14 is involved in 28S subunit biogenesis and mtDNA maintenance. (PMID:22447445)
• Our results uncovered an unexpected, mandatory detour of NOA1 through the nucleolus before uptake into mitochondria. (PMID:25072814)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	noa1	ENSDARG00000102934
mus_musculus	Noa1	ENSMUSG00000036285
rattus_norvegicus	Noa1	ENSRNOG00000002055
drosophila_melanogaster	CG10914	FBGN0034307
caenorhabditis_elegans		WBGENE00013001

Paralogs (6): LSG1 (ENSG00000041802), GNL3L (ENSG00000130119), GNL2 (ENSG00000134697), MTG1 (ENSG00000148824), GNL3 (ENSG00000163938), GNL1 (ENSG00000204590)

Protein

Protein identifiers

Nitric oxide-associated protein 1 — Q8NC60 (reviewed: Q8NC60)

All UniProt accessions (1): Q8NC60

UniProt curated annotations — full annotation on UniProt →

Function. Involved in regulation of mitochondrial protein translation and respiration. Plays a role in mitochondria-mediated cell death. May act as a scaffolding protein or stabilizer of respiratory chain supercomplexes. Binds GTP.

Subunit / interactions. Homodimer or multimer. Interacts with mitochondrial complex I, DAP3, MRPL12 and MRPS27.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the TRAFAC class YlqF/YawG GTPase family. NOA1 subfamily.

RefSeq proteins (1): NP_115689* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006073	GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030378	G_CP_dom	Domain
IPR048422	NOA1/YqeH-like_C	Domain
IPR052807	Mito_transl_resp_regulator	Family

Pfam: PF01926, PF21516

UniProt features (55 total): strand 22, helix 17, sequence conflict 3, region of interest 3, turn 3, sequence variant 3, chain 1, domain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8CSP	ELECTRON MICROSCOPY	2.66
9H54	ELECTRON MICROSCOPY	3
9H51	ELECTRON MICROSCOPY	3.1
9G5B	ELECTRON MICROSCOPY	3.2
9H55	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NC60-F1	74.04	0.30

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 (1): 77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): GOBP_RIBOSOME_BIOGENESIS, TGCGCANK_UNKNOWN, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_RIBOSOME_ASSEMBLY, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANELLE_ASSEMBLY, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, IK3_01, HEIDENBLAD_AMPLICON_12P11_12_DN, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RIBOSOMAL_SMALL_SUBUNIT_ASSEMBLY, GOCC_LUMENAL_SIDE_OF_MEMBRANE

GO Biological Process (4): apoptotic process (GO:0006915), mitochondrion organization (GO:0007005), mitochondrial ribosome assembly (GO:0061668), mitochondrial small ribosomal subunit assembly (GO:0180026)

GO Molecular Function (5): RNA binding (GO:0003723), GTP binding (GO:0005525), RNA folding chaperone (GO:0140691), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), membrane (GO:0016020), matrix side of mitochondrial inner membrane (GO:0099617)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
organelle organization	1
ribosome assembly	1
ribosomal small subunit assembly	1
mitochondrial ribosome assembly	1
nucleic acid binding	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
molecular_function	1
RNA folding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1
mitochondrial inner membrane	1
lumenal side of membrane	1

Protein interactions and networks

STRING

2859 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOA1	MTG2	Q9H4K7	869
NOA1	MTG1	Q9BT17	822
NOA1	ERAL1	O75616	776
NOA1	POLR2B	P30876	666
NOA1	MALSU1	Q96EH3	653
NOA1	GTPBP10	A4D1E9	646
NOA1	TFAM	Q00059	605
NOA1	NSUN4	Q96CB9	592
NOA1	MRPS7	Q9Y2R9	589
NOA1	MTERF4	Q7Z6M4	576
NOA1	IGFBP7	Q16270	559
NOA1	DAP3	P51398	544
NOA1	GTPBP8	Q8N3Z3	535
NOA1	DDX28	Q9NUL7	527
NOA1	GTPBP6	O43824	505

IntAct

126 interactions, top by confidence:

A	B	Type	Score
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
DAP3	NOA1	psi-mi:“MI:0915”(physical association)	0.700
NOA1	DAP3	psi-mi:“MI:0407”(direct interaction)	0.700
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
MRPS27	MRPS14	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
MRPS6	STAT5A	psi-mi:“MI:0914”(association)	0.550
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
TRMT10B	MRPS14	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
CCDC59	GAPDHS	psi-mi:“MI:0914”(association)	0.530
MRPS34	ZZEF1	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
NOA1	ATE1	psi-mi:“MI:0914”(association)	0.530
MRPS15	PRKACG	psi-mi:“MI:0914”(association)	0.530
MRPS27	YBX1	psi-mi:“MI:0914”(association)	0.530
MRPS34	MRPS12	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
MRPS26	MRPS10	psi-mi:“MI:0914”(association)	0.530
NOA1	NDUFA9	psi-mi:“MI:0915”(physical association)	0.500
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
AURKAIP1	NRDC	psi-mi:“MI:0914”(association)	0.480

BioGRID (123): NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Affinity Capture-MS), NOA1 (Proximity Label-MS), NOA1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A1L1F1, A2AIL4, A4IHH4, A4QP75, B3MGZ0, B4GGT6, F6ZFR0, O00746, O08776, O55137, O55171, O88202, O88267, P36776, P49753, P87355, Q28CM7, Q32LB9, Q330K2, Q3B8B2, Q3T056, Q4R816, Q4VK78, Q566Y1, Q58DL1, Q59HJ6, Q5EBA1, Q5RJV0, Q6DFN1, Q80YD1, Q810S1, Q86U10, Q8BWN8, Q8CGK3, Q8HY87, Q8NC60, Q924S5, Q96BQ1, Q99KK9

Diamond homologs: Q32LB9, Q8NC60, Q9JJG9, Q8W4I6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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
Mitochondrial ribosome-associated quality control	23	32.1×	1e-26
Mitochondrial translation initiation	21	30.3×	6e-24
Mitochondrial translation elongation	21	30.3×	6e-24
Mitochondrial translation	19	29.7×	2e-21
Mitochondrial translation termination	21	26.2×	1e-22
Translation	20	14.1×	5e-16

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	22	32.4×	7e-25
translation	13	11.3×	4e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	17
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1266 predictions. Top by Δscore:

Variant	Effect	Δscore
4:56964530:CCAA:C	acceptor_gain	1.0000
4:56964531:C:CT	acceptor_gain	1.0000
4:56964532:A:T	acceptor_gain	1.0000
4:56964533:A:AC	acceptor_gain	1.0000
4:56964533:A:C	acceptor_gain	1.0000
4:56964538:A:AC	acceptor_gain	1.0000
4:56973142:ACAT:A	donor_loss	1.0000
4:56973144:ATACA:A	donor_loss	1.0000
4:56973145:TA:T	donor_loss	1.0000
4:56973146:A:AC	donor_gain	1.0000
4:56973146:A:C	donor_loss	1.0000
4:56973147:C:CC	donor_gain	1.0000
4:56973147:CA:C	donor_gain	1.0000
4:56973147:CACA:C	donor_gain	1.0000
4:56973147:CACAA:C	donor_gain	1.0000
4:56973350:CTTC:C	acceptor_gain	1.0000
4:56973352:TCCT:T	acceptor_loss	1.0000
4:56973353:CCTAG:C	acceptor_loss	1.0000
4:56973354:C:CC	acceptor_gain	1.0000
4:56973354:CT:C	acceptor_loss	1.0000
4:56973355:T:G	acceptor_loss	1.0000
4:56973853:CTTA:C	donor_loss	1.0000
4:56973856:A:AT	donor_loss	1.0000
4:56973857:C:CG	donor_loss	1.0000
4:56973857:CCTA:C	donor_gain	1.0000
4:56974021:ACCTG:A	acceptor_loss	1.0000
4:56974023:C:T	acceptor_loss	1.0000
4:56974024:T:C	acceptor_loss	1.0000
4:56963658:CAAC:C	acceptor_gain	0.9900
4:56963659:AACC:A	acceptor_loss	0.9900

AlphaMissense

4491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:56976534:T:A	K351I	0.997
4:56976635:G:C	S317R	0.997
4:56976635:G:T	S317R	0.997
4:56976637:T:G	S317R	0.997
4:56973997:A:C	F390L	0.996
4:56973997:A:T	F390L	0.996
4:56973999:A:G	F390L	0.996
4:56976840:T:A	K249I	0.996
4:56973176:T:G	D496A	0.995
4:56976505:A:G	S361P	0.994
4:56963659:A:G	W630R	0.993
4:56963659:A:T	W630R	0.993
4:56968400:C:G	R544P	0.993
4:56973175:G:C	D496E	0.993
4:56973175:G:T	D496E	0.993
4:56973176:T:C	D496G	0.993
4:56976521:A:C	F355L	0.993
4:56976521:A:T	F355L	0.993
4:56976523:A:G	F355L	0.993
4:56976633:G:T	A318D	0.993
4:56973176:T:A	D496V	0.992
4:56973177:C:G	D496H	0.992
4:56973958:C:A	R403S	0.992
4:56973958:C:G	R403S	0.992
4:56973998:A:G	F390S	0.992
4:56976531:G:A	S352F	0.992
4:56976842:G:C	N248K	0.991
4:56976842:G:T	N248K	0.991
4:56973959:C:G	R403T	0.990
4:56976532:A:G	S352P	0.990

dbSNP variants (sampled 300 via entrez): RS1000036418 (4:56973740 T>G), RS1000087036 (4:56974326 G>T), RS1000148356 (4:56978691 A>G), RS1000277479 (4:56967035 T>G), RS1000454733 (4:56978308 C>T), RS1000691560 (4:56967268 T>A), RS1001064612 (4:56966029 T>C), RS1001347204 (4:56964827 G>A,T), RS1001414043 (4:56966283 C>T), RS1001521554 (4:56970868 T>G), RS1001657776 (4:56974400 C>G,T), RS1001802904 (4:56969725 A>T), RS1001966351 (4:56962991 G>A,C), RS10032625 (4:56963048 C>G,T), RS1003270368 (4:56976167 C>G)

Disease associations

OMIM: gene MIM:614919 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000882_3	Response to bleomycin (chromatid breaks)	9.000000e-07
GCST001232_2	Age-related macular degeneration	2.000000e-08
GCST002647_24	Height	7.000000e-17
GCST003116_1	Coronary artery disease	5.000000e-08
GCST004787_2	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	8.000000e-08
GCST005195_148	Coronary artery disease	1.000000e-08
GCST005196_116	Coronary artery disease	2.000000e-09
GCST005991_80	Platelet count	2.000000e-11
GCST007329_5	Automobile speeding propensity	1.000000e-10
GCST008163_175	Height	1.000000e-07
GCST90002397_9	Mean spheric corpuscular volume	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007593	chromatid break measurement
EFO:0004309	platelet count
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression, decreases expression	2
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzophenoneidum	increases expression	1
Carbamazepine	affects expression	1
Diazinon	increases methylation	1
Naled	affects expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tamoxifen	increases activity	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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