NAF1

Summary

NAF1 (nuclear assembly factor 1 ribonucleoprotein, HGNC:25126) is a protein-coding gene on chromosome 4q32.2, encoding H/ACA ribonucleoprotein complex non-core subunit NAF1 (Q96HR8). RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. It is a selective cancer dependency (DepMap: 37.3% of cell lines).

Enables identical protein binding activity and telomerase RNA binding activity. Involved in ribosome biogenesis; telomerase RNA stabilization; and telomerase holoenzyme complex assembly. Acts upstream of or within telomerase RNA localization to Cajal body. Located in cytoplasm and nucleoplasm. Part of sno(s)RNA-containing ribonucleoprotein complex. Implicated in melanoma.

Source: NCBI Gene 92345 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7 (Definitive, ClinGen)
• Clinical variants (ClinVar): 316 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 37.3% of screened cell lines
• MANE Select transcript: NM_138386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25126
Approved symbol	NAF1
Name	nuclear assembly factor 1 ribonucleoprotein
Location	4q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145414
Ensembl biotype	protein_coding
OMIM	617868
Entrez	92345

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 retained_intron

ENST00000274054, ENST00000422287, ENST00000502973, ENST00000509232, ENST00000509434, ENST00000509884, ENST00000851281, ENST00000851282

RefSeq mRNA: 2 — MANE Select: NM_138386 NM_001128931, NM_138386

CCDS: CCDS3803, CCDS47159

Canonical transcript exons

ENST00000274054 — 8 exons

Exon	Start	End
ENSE00000970445	163133154	163133256
ENSE00000970446	163128669	163129348
ENSE00002064568	163166363	163166890
ENSE00003499186	163140223	163140383
ENSE00003517213	163145782	163145864
ENSE00003562137	163148341	163148434
ENSE00003640619	163137199	163137250
ENSE00003645204	163164217	163164391

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 88.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9118 / max 289.4788, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54662	20.5051	1808
54661	0.4067	149

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial artery	UBERON:0007610	88.30	gold quality
popliteal artery	UBERON:0002250	88.29	gold quality
gastrocnemius	UBERON:0001388	87.76	gold quality
muscle of leg	UBERON:0001383	86.72	gold quality
left uterine tube	UBERON:0001303	86.48	gold quality
colonic epithelium	UBERON:0000397	86.39	gold quality
aorta	UBERON:0000947	86.13	gold quality
left ovary	UBERON:0002119	85.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.75	gold quality
skin of abdomen	UBERON:0001416	85.57	gold quality
epithelial cell of pancreas	CL:0000083	85.54	silver quality
right ovary	UBERON:0002118	85.36	gold quality
skin of leg	UBERON:0001511	84.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.57	gold quality
omental fat pad	UBERON:0010414	84.26	gold quality
peritoneum	UBERON:0002358	84.21	gold quality
skeletal muscle organ	UBERON:0014892	84.12	gold quality
right uterine tube	UBERON:0001302	84.10	gold quality
zone of skin	UBERON:0000014	84.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.97	gold quality
ovary	UBERON:0000992	83.85	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.71	gold quality
descending thoracic aorta	UBERON:0002345	83.57	gold quality
thoracic aorta	UBERON:0001515	83.44	gold quality
ascending aorta	UBERON:0001496	83.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.33	gold quality
left testis	UBERON:0004533	83.31	gold quality
adrenal tissue	UBERON:0018303	83.27	gold quality
tibial nerve	UBERON:0001323	83.24	gold quality
right testis	UBERON:0004534	83.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting NAF1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-8055	97.62	66.09	1023

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• Telomere length is associated with Esophageal squamous cell carcinoma risk in a U-shaped pattern and demonstrates that TL-SNPs may not be important in carcinogenesis in Chinese population. (PMID:26581417)
• Data indicate that disease in NAF1 mutation carriers is telomere-mediated; they show that NAF1 haploinsufficiency selectively disturbs telomere length homeostasis by decreasing the levels of telomerase RNA while sparing rRNA pseudouridylation. (PMID:27510903)
• These findings point to a key role for the unique 3Cys-1His cluster of NAF-1 in promoting rapid tumor growth through cellular resistance to oxidative stress. (PMID:27621439)
• the current study has identified that rs2320615 in the NAF1 was associated with the risk of esophageal cancer in the Han Chinese population. (PMID:28454086)
• Study presents a novel genome-wide candidate for ductal adenocarcinoma (PDAC) - TERT-rs2736100 and a completely new signal for PDAC in NAF1-rs7675998 that approaches the genome-wide threshold. In addition, study found a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. (PMID:30325019)
• NAF1 rs4691896 Is Significantly Associated with Coal Workers’ Pneumoconiosis in a Chinese Han Population: A Case-Control Study. (PMID:32333749)
• Telomere Length and Male Fertility. (PMID:33921254)
• Colorectal cancer-associated SNP rs17042479 is involved in the regulation of NAF1 promoter activity. (PMID:36067202)
• Relationship between common telomere length-related genetic variations, telomere length, and risk of antituberculosis drug-induced hepatotoxicity in Chinese Han population: As assessed for causality using the updated Roussel Uclaf Causality Assessment Method. (PMID:36855016)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	naf1	ENSDARG00000057929
mus_musculus	Naf1	ENSMUSG00000014907
rattus_norvegicus	Naf1	ENSRNOG00000026403
drosophila_melanogaster	CG10341	FBGN0032701
caenorhabditis_elegans		WBGENE00009132

Protein

Protein identifiers

H/ACA ribonucleoprotein complex non-core subunit NAF1 — Q96HR8 (reviewed: Q96HR8)

All UniProt accessions (2): D6RIB3, Q96HR8

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex and disappears during maturation of the complex and is replaced by NOLA1/GAR1 to yield mature H/ACA snoRNPs complex. Probably competes with NOLA1/GAR1 for binding with DKC1/NOLA4.

Subunit / interactions. During assembly of the complex, component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs) which contains NOLA2/NHP2, NOLA3/NOP10, NAF1 and DKC1/NOLA4. Interacts directly with DKC1/NOLA4.

Subcellular location. Cytoplasm. Nucleus.

Disease relevance. Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 7 (PFBMFT7) [MIM:620365] An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other features include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk. Phenotype, age at onset, and severity are determined by telomere length. PFBMFT7 patients manifest anemia, lymphopenia, liver involvement with portal hypertension and hepatopulmonary syndrome, premature graying of the hair, nail dystrophy, and predisposition to squamous cell cancers or myelodysplasia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NAF1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96HR8-1	1	yes
Q96HR8-2	2

RefSeq proteins (2): NP_001122403, NP_612395* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007504	H/ACA_rnp_Gar1/Naf1	Family
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR038664	Gar1/Naf1_Cbf5-bd_sf	Homologous_superfamily
IPR040309	Naf1	Family

Pfam: PF04410

UniProt features (26 total): compositionally biased region 7, strand 7, region of interest 3, modified residue 2, splice variant 2, sequence variant 2, chain 1, cross-link 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EQN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HR8-F1	61.91	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.

Post-translational modifications (3): 1, 315, 338

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 194 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, chr4q32, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_PSEUDOURIDINE_SYNTHESIS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION

GO Biological Process (12): snoRNA guided rRNA pseudouridine synthesis (GO:0000454), box H/ACA snoRNP assembly (GO:0000493), positive regulation of telomere maintenance via telomerase (GO:0032212), ribosome biogenesis (GO:0042254), RNA stabilization (GO:0043489), telomerase RNA stabilization (GO:0090669), telomerase RNA localization to Cajal body (GO:0090671), positive regulation of telomere maintenance via telomere lengthening (GO:1904358), telomerase holoenzyme complex assembly (GO:1905323), pseudouridine synthesis (GO:0001522), rRNA processing (GO:0006364), protein-RNA complex assembly (GO:0022618)

GO Molecular Function (4): RNA binding (GO:0003723), identical protein binding (GO:0042802), telomerase RNA binding (GO:0070034), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), sno(s)RNA-containing ribonucleoprotein complex (GO:0005732), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoprotein complex biogenesis	2
cellular anatomical structure	2
rRNA pseudouridine synthesis	1
small nucleolar ribonucleoprotein complex assembly	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
regulation of RNA stability	1
negative regulation of RNA catabolic process	1
RNA stabilization	1
RNA localization to Cajal body	1
telomerase RNA localization	1
telomere maintenance via telomere lengthening	1
positive regulation of telomere maintenance	1
regulation of telomere maintenance via telomere lengthening	1
protein-RNA complex assembly	1
RNA modification	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
protein-containing complex assembly	1
protein-RNA complex organization	1
nucleic acid binding	1
protein binding	1
RNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAF1	SHQ1	Q6PI26	729
NAF1	GAR1	Q9NY12	575
NAF1	TESMIN	Q9Y4I5	563
NAF1	ARFGAP3	Q9NP61	497
NAF1	DKC1	O60832	490
NAF1	TERT	O14746	466
NAF1	ZNF208	O43345	451
NAF1	RTEL1	Q9NZ71	448
NAF1	EMCN	Q9ULC0	439
NAF1	ACYP2	P14621	415
NAF1	STN1	Q9H668	391
NAF1	TINF2	Q9BSI4	384
NAF1	NOP10	Q9NPE3	353
NAF1	NHP2	Q9NX24	353
NAF1	ARFRP1	Q13795	352

IntAct

179 interactions, top by confidence:

A	B	Type	Score
DKC1	NAF1	psi-mi:“MI:0914”(association)	0.900
NAF1	DKC1	psi-mi:“MI:0914”(association)	0.900
NAF1	DKC1	psi-mi:“MI:0403”(colocalization)	0.900
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
SNX33	NAF1	psi-mi:“MI:0915”(physical association)	0.670
DKC1	SHQ1	psi-mi:“MI:0914”(association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
NUAK2	PPP1R12A	psi-mi:“MI:0914”(association)	0.640
RBFOX2	NAF1	psi-mi:“MI:0915”(physical association)	0.560
DAB1	NAF1	psi-mi:“MI:0915”(physical association)	0.560
FAM168A	NAF1	psi-mi:“MI:0915”(physical association)	0.560
NAF1	DAB1	psi-mi:“MI:0915”(physical association)	0.560
NAF1	FUBP1	psi-mi:“MI:0915”(physical association)	0.560
NAF1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.560
FUBP1	NAF1	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	NAF1	psi-mi:“MI:0915”(physical association)	0.560
BOLL	NAF1	psi-mi:“MI:0915”(physical association)	0.560
DAZAP2	NAF1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (173): NAF1 (Two-hybrid), NAF1 (Two-hybrid), NAF1 (Two-hybrid), NAF1 (Affinity Capture-MS), NAF1 (Affinity Capture-MS), NAF1 (Affinity Capture-MS), NAF1 (Affinity Capture-MS), NAF1 (Co-fractionation), NHP2 (Co-fractionation), NAF1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), FKBP1A (Affinity Capture-MS), MTOR (Affinity Capture-MS), HADHA (Affinity Capture-MS), HADHB (Affinity Capture-MS)

ESM2 similar proteins: A6ZRW0, B2RRE7, B5DEB9, E9Q2Z1, O08623, O18870, P43243, P43244, P53919, P61129, P97868, Q01804, Q03173, Q08E13, Q09003, Q13501, Q1LVK9, Q32NQ8, Q3UIW5, Q3UMQ8, Q4V7K4, Q52KK4, Q5DTV4, Q5F3D1, Q5HYM0, Q5R789, Q5RBA5, Q5XI59, Q641W3, Q64337, Q6A037, Q6DD45, Q6DJS0, Q6NZY4, Q7Z6E9, Q7ZXG4, Q80XI3, Q8BWW4, Q8BYK8, Q8K310

Diamond homologs: A6ZRW0, O14360, P53919, Q96HR8, Q3UMQ8, Q52KK4, Q9VJ62

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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
Neurexins and neuroligins	6	14.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	192
Likely benign	84
Benign	6

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2501711	NM_138386.3(NAF1):c.984dup (p.Ser329fs)	Pathogenic
2501712	NM_138386.3(NAF1):c.956_957del (p.Lys319fs)	Pathogenic
1338525	NM_138386.3(NAF1):c.1033+1G>T	Likely pathogenic
2443184	NM_138386.3(NAF1):c.1033+1G>A	Likely pathogenic
2443185	NM_138386.3(NAF1):c.691A>T (p.Lys231Ter)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3206 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:163133242:A:C	S315R	0.999
4:163133242:A:T	S315R	0.999
4:163133244:T:G	S315R	0.999
4:163137228:A:G	W301R	0.999
4:163137228:A:T	W301R	0.999
4:163140367:C:T	G245E	0.999
4:163140361:A:T	V247D	0.998
4:163145810:A:G	F230S	0.998
4:163145831:A:T	V223D	0.998
4:163148343:A:G	L211P	0.998
4:163148364:A:T	V204D	0.998
4:163148370:C:T	G202E	0.998
4:163133245:A:C	F314L	0.997
4:163133245:A:T	F314L	0.997
4:163133247:A:G	F314L	0.997
4:163137231:A:G	S300P	0.997
4:163140274:G:T	A276D	0.997
4:163140382:A:T	I240K	0.997
4:163145864:A:T	V212E	0.997
4:163148371:C:A	G202W	0.997
4:163133243:C:T	S315N	0.996
4:163137226:C:A	W301C	0.996
4:163137226:C:G	W301C	0.996
4:163137233:G:T	A299E	0.996
4:163137234:C:G	A299P	0.996
4:163137236:T:C	D298G	0.996
4:163140382:A:C	I240R	0.996
4:163145786:C:T	G238E	0.996
4:163148371:C:G	G202R	0.996
4:163148371:C:T	G202R	0.996

dbSNP variants (sampled 300 via entrez): RS1000164846 (4:163152495 C>G), RS1000218229 (4:163143689 G>C), RS1000219305 (4:163107964 G>A), RS1000226785 (4:163163834 G>A), RS1000229092 (4:163120194 A>G), RS1000327065 (4:163161177 A>G,T), RS1000391848 (4:163126456 G>C), RS1000397132 (4:163139407 T>C), RS1000397215 (4:163114177 T>C), RS1000417737 (4:163129065 T>A,G), RS1000457298 (4:163136986 A>C), RS1000501581 (4:163151300 A>T), RS1000524031 (4:163144871 A>G,T), RS1000525839 (4:163109456 A>G), RS1000555667 (4:163145266 T>A)

Disease associations

OMIM: gene MIM:617868 | disease phenotypes: MIM:620365

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7	Definitive	AD

Mondo (2): pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7 (MONDO:0957261), pulmonary fibrosis (MONDO:0002771)

Orphanet (0):

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000938	Osteopenia
HP:0001409	Portal hypertension
HP:0001873	Thrombocytopenia
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0002097	Emphysema
HP:0002206	Pulmonary fibrosis
HP:0002216	Premature graying of hair
HP:0002863	Myelodysplasia
HP:0003596	Middle age onset
HP:0006739	Squamous cell carcinoma of the skin
HP:0008404	Nail dystrophy
HP:0011462	Young adult onset
HP:0100651	Type I diabetes mellitus

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011658	Pulmonary Fibrosis	C08.381.483.652; C23.550.355.644

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724617 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.10	Kd	8	nM	MOLIBRESIB
7.70	IC50	20	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179105: Binding affinity against NAF1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0080	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Valproic Acid	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	decreases expression	1
Bortezomib	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Fluorouracil	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Ribonucleotides	affects binding	1
Rifampin	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697144	Binding	Inhibition of NAF1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT07570888	PHASE4	NOT_YET_RECRUITING	This is a Trial Designed to Evaluate the Combination of Nerandomilast With Mycophenolate Across a Wide Variety of Pulmonary Fibrosis Subtypes, With the Aim of Providing Clinicians With Assurance That This is an Appropriate Therapeutic Combination.
NCT00004563	PHASE3	COMPLETED	Scleroderma Lung Disease
NCT00052039	PHASE3	TERMINATED	A Randomized, Double-Blind, Three-Arm, Phase 3b Study Comparing the Safety and Efficacy of Interferon Gamma-1b With Azathioprine, and Azathioprine Alone in Patients With IPF Receiving Prednisone
NCT00075998	PHASE3	TERMINATED	The INSPIRE Trial: A Study of Interferon Gamma-1b for Idiopathic Pulmonary Fibrosis (IPF)
NCT00076635	PHASE3	TERMINATED	An Open-Label Study of the Safety of Interferon Gamma-1b in Patients With IPF
NCT00517933	PHASE3	COMPLETED	Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
NCT00639496	PHASE3	COMPLETED	Study of the Effects of High-dose N-acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)
NCT00650091	PHASE3	COMPLETED	Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF
NCT00896155	PHASE3	UNKNOWN	Trial of Concurrent Versus Sequential Tamoxifen With Radiotherapy in Breast Cancer Patients
NCT01335464	PHASE3	COMPLETED	Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients
NCT01335477	PHASE3	COMPLETED	Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT03267108	PHASE3	TERMINATED	A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT04979884	PHASE3	COMPLETED	Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT06025578	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis
NCT06238622	PHASE3	RECRUITING	A Follow-up Study to Test Long-term Treatment With Nerandomilast in People With Pulmonary Fibrosis Who Took Part in a Previous Study With Nerandomilast
NCT07201922	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis
NCT07441408	PHASE3	NOT_YET_RECRUITING	Long-term Extension Study to Evaluate Safety and Tolerability of Admilparant in Participants With Pulmonary Fibrosis
NCT07503587	PHASE3	NOT_YET_RECRUITING	Evaluating the Efficacy and Safety of of HSK44459 in People With Progressive Pulmonary Fibrosis
NCT00000596	PHASE2	COMPLETED	Diffuse Fibrotic Lung Disease
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT00052052	PHASE2	COMPLETED	An Open-Label Study of the Safety and Efficacy of Subcutaneous Recombinant Interferon-Gamma 1b (IFN-Gamma 1b) in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT00063869	PHASE2	COMPLETED	Study Evaluating the Safety and Efficacy of Etanercept in Patients With Idiopathic Pulmonary Fibrosis
NCT00080223	PHASE2	COMPLETED	Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis
NCT00109681	PHASE2	COMPLETED	Inhaled Iloprost in Adults With Abnormal Pulmonary Pressure and Associated With Idiopathic Pulmonary Fibrosis
NCT00352482	PHASE2	COMPLETED	Sildenafil to Increase Exercise Capacity in Individuals With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension
NCT00455767	PHASE2	COMPLETED	Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients
NCT00514683	PHASE2	COMPLETED	Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis
NCT00690885	PHASE2	TERMINATED	Interferon-alpha Treatment of Chronic Cough in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis
NCT00786201	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF)
NCT01135199	PHASE2	WITHDRAWN	Pomalidomide for Cough in Patients With Idiopathic Pulmonary Fibrosis
NCT01170065	PHASE2	COMPLETED	Roll Over Study From 1199.30 BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01203943	PHASE2	TERMINATED	A Study to Characterize the Safety, PK and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01417156	PHASE2	COMPLETED	Safety and PK Study of BIBF 1120 in Japanese Patients With IPF: Follow up Study From 1199.31(NCT01136174)
NCT01442779	PHASE2	COMPLETED	Clinical Trial of Low Dose Oral Interferon Alpha in Idiopathic Pulmonary Fibrosis
NCT01917877	PHASE2	UNKNOWN	Efficiency Study for Acute Radiation-induced and Chemotherapy-induced Pulmonary Fibrosis With Bevasizumab
NCT02603068	PHASE2	WITHDRAWN	Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis