PARN

Summary

PARN (poly(A)-specific ribonuclease, HGNC:8609) is a protein-coding gene on chromosome 16p13.12, encoding Poly(A)-specific ribonuclease PARN (O95453). 3’-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. It is a selective cancer dependency (DepMap: 26.3% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a 3’-exoribonuclease, with similarity to the RNase D family of 3’-exonucleases. It prefers poly(A) as the substrate, hence, efficiently degrades poly(A) tails of mRNAs. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs. This protein is also involved in silencing of certain maternal mRNAs during oocyte maturation and early embryonic development, as well as in nonsense-mediated decay (NMD) of mRNAs that contain premature stop codons. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5073 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 998 total — 54 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 108
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 26.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002582

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8609
Approved symbol	PARN
Name	poly(A)-specific ribonuclease
Location	16p13.12
Locus type	gene with protein product
Status	Approved
Aliases	DAN
Ensembl gene	ENSG00000140694
Ensembl biotype	protein_coding
OMIM	604212
Entrez	5073

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 30 protein_coding, 10 protein_coding_CDS_not_defined, 8 nonsense_mediated_decay, 5 retained_intron

ENST00000341484, ENST00000420015, ENST00000437198, ENST00000538472, ENST00000539279, ENST00000562715, ENST00000562896, ENST00000563155, ENST00000563641, ENST00000563697, ENST00000564113, ENST00000564882, ENST00000564904, ENST00000566021, ENST00000569444, ENST00000650960, ENST00000650990, ENST00000651027, ENST00000651049, ENST00000651241, ENST00000651300, ENST00000651348, ENST00000651634, ENST00000651760, ENST00000651865, ENST00000651913, ENST00000652051, ENST00000652066, ENST00000652411, ENST00000652501, ENST00000652541, ENST00000652727, ENST00000697471, ENST00000697472, ENST00000697473, ENST00000697474, ENST00000697475, ENST00000697476, ENST00000697477, ENST00000874414, ENST00000874415, ENST00000874416, ENST00000874417, ENST00000874418, ENST00000874419, ENST00000874420, ENST00000874421, ENST00000931608, ENST00000931609, ENST00000931610, ENST00000931611, ENST00000960023, ENST00000960024

RefSeq mRNA: 3 — MANE Select: NM_002582 NM_001134477, NM_001242992, NM_002582

CCDS: CCDS45419, CCDS45420, CCDS58425

Canonical transcript exons

ENST00000437198 — 24 exons

Exon	Start	End
ENSE00001131091	14446888	14447081
ENSE00001422402	14435701	14436772
ENSE00002616202	14630107	14630260
ENSE00003458735	14609058	14609123
ENSE00003477505	14610644	14610809
ENSE00003477581	14482638	14482827
ENSE00003480515	14554065	14554151
ENSE00003529786	14628172	14628251
ENSE00003537452	14627269	14627336
ENSE00003539758	14629597	14629674
ENSE00003547229	14606484	14606526
ENSE00003589533	14580874	14580943
ENSE00003589608	14582181	14582291
ENSE00003614729	14593301	14593378
ENSE00003615689	14608281	14608319
ENSE00003619137	14604146	14604226
ENSE00003627614	14552021	14552095
ENSE00003652859	14617590	14617650
ENSE00003655474	14599904	14599960
ENSE00003669596	14584749	14584791
ENSE00003681443	14627106	14627187
ENSE00003682839	14584347	14584422
ENSE00003693789	14586318	14586361
ENSE00003787741	14555654	14555709

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.5120 / max 354.0304, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156368	32.3821	1821
156371	1.8143	609
156369	1.1040	702
156370	0.2115	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.43	gold quality
corpus callosum	UBERON:0002336	92.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.66	gold quality
tonsil	UBERON:0002372	91.60	gold quality
colonic epithelium	UBERON:0000397	91.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.98	gold quality
bone marrow cell	CL:0002092	90.67	gold quality
adrenal tissue	UBERON:0018303	90.40	gold quality
smooth muscle tissue	UBERON:0001135	90.39	gold quality
islet of Langerhans	UBERON:0000006	90.22	gold quality
urinary bladder	UBERON:0001255	89.45	gold quality
rectum	UBERON:0001052	89.42	gold quality
right adrenal gland cortex	UBERON:0035827	89.36	gold quality
right adrenal gland	UBERON:0001233	89.28	gold quality
popliteal artery	UBERON:0002250	89.20	gold quality
tibial artery	UBERON:0007610	89.20	gold quality
placenta	UBERON:0001987	89.00	gold quality
lymph node	UBERON:0000029	88.95	gold quality
adrenal gland	UBERON:0002369	88.95	gold quality
endometrium	UBERON:0001295	88.65	gold quality
uterine cervix	UBERON:0000002	88.57	gold quality
left adrenal gland	UBERON:0001234	88.56	gold quality
left adrenal gland cortex	UBERON:0035825	88.35	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.35	gold quality
right lung	UBERON:0002167	88.34	gold quality
lower esophagus	UBERON:0013473	88.33	gold quality
leukocyte	CL:0000738	88.31	gold quality
monocyte	CL:0000576	88.25	gold quality
ventricular zone	UBERON:0003053	88.14	gold quality
mucosa of stomach	UBERON:0001199	87.97	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)

30 targeting PARN, 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-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-11401	90.58	63.72	128
HSA-MIR-95-3P	89.95	66.87	81

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 26.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Deadenylation by the mammalian and amphibian poly(A)-specific exoribonuclease, PARN, is stimulated by the presence of an m(7)-guanosine cap on substrate RNAs. PARN exhibits intrinsic cap-binding activity. (PMID:10698948)
• PARN binds to the 5’ cap on substrate mRNAs. Cap-binding is stimulated by a poly(A) tail and competed by eIF4E. Cap-PARN interactions integrate regulated mRNA stability and translation. (PMID:10882133)
• The m7GpppG cap has multiple effects on PARN activity. In cis, the 5’cap stimulates deadenylation by increasing PARN processivity. In trans, low concentrations of cap stimulate PARN activity whereas high concentrations inhibit deadenylation. (PMID:11359775)
• Xenopus oocytes contain cytoplasmic (p62) and nuclear (p74) isoforms of PARN. p62 is proteolytically derived from p74. Both isoforms are expressed throughout oogenesis and early development. (PMID:11424938)
• residues of human PARN, Asp(28), Glu(30), Asp(292), and Asp(382), are essential for catalysis but are not required for stabilization of the PARN x RNA substrate complex. (PMID:11742007)
• Results show that tristetraprolin can promote the deadenylation of AU-rich element (ARE)-containing, polyadenylated substrates by poly(A) RNase. (PMID:12748283)
• study of binding and coordination of divalent metal ions in the active site of PARN (PMID:15358788)
• The crystal structure of C-terminal truncated human PARN determined in two states (free and RNA-bound forms) reveals that PARN is folded into two domains, an R3H domain and a nuclease domain (PMID:16281054)
• Association of CBC with PARN might have importance in the regulated recruitment of PARN to the nonsense-mediated decay pathway during the pioneer round of translation. (PMID:16317009)
• CUG-BP binds specifically to both of these RNAs and stimulates poly(A) shortening by PARN. Moreover, CUG-BP interacts with PARN in extracts by coimmunoprecipitation, and this interaction can be recapitulated using recombinant proteins (PMID:16601207)
• The entire RNA-recognition motif (RRM) domain not only contributes to the substrate binding and efficient catalysis of PARN, but also stabilizes the overall structures of the protein. (PMID:17391638)
• REsults describe the crystal structure of the poly(A)-specific ribonuclease (PARN)-RRM domain with a bound 7-methylguanosine triphosphate nucleotide, revealing a novel binding mode for the m(7)G cap. (PMID:18694759)
• PARN is an allosteric enzyme, and potassium ions and the cap analogue are effectors with binding sites located at the RRM domain. (PMID:19103158)
• PARN harbors specificity for adenosine recognition in its active site and that the nucleotides surrounding the scissile bond are critical for adenosine recognition. (PMID:19901024)
• The atomic force microscopy images of single PARN molecules reveal compact ellipsoidal dimers (10.9 x 7.6 x 4.6nm). (PMID:21741754)
• poly(A) polymerase Gld2, deadenylase PARN, and translation inhibitory factor neuroguidin (Ngd) are components of a dendritic CPEB-associated polyadenylation apparatus (PMID:22727665)
• Both R3H and RRM domains were essential for the high affinity of long poly(A) substrate. (PMID:23388391)
• poly(A)-specific ribonuclease (PARN) was upregulated in gastric tumor tissues and gastric cancer cell lines MKN28 and AGS. (PMID:25499764)
• PARN and RTEL1 mutation carriers had shortened leukocyte telomere lengths. (PMID:25848748)
• 3 families with dyskeratosis congenita had key domain mutations in PARN shortening telomeres, reducing deadenylation, and downregulating TERC, DKC1, RTEL1, and TERF1. (PMID:25893599)
• The results indicate that the cellular level of miR-122 is determined by the balance between the opposing effects of GLD-2 and PARN/CUGBP1 on the metabolism of its 3’-terminus. (PMID:26130707)
• Large monoallelic mutations of PARN can cause developmental/mental illness. Biallelic PARN mutations cause severe bone marrow failure and central hypomyelination. (PMID:26342108)
• Mutations in the PARN gene cause dyskeratosis congenital. (PMID:26482878)
• results highlight the clinical significance of PARN and NOC on the survival in SCC diagnosed patients. (PMID:26541675)
• we found a polyadenylation-dependent 3’ end maturation pathway for the human telomerase RNA that relies on the nuclear poly(A)-binding protein PABPN1 and the poly(A)-specific RNase PARN. (PMID:26628368)
• Studies suggest that the effects of poly(A)-specific ribonuclease (PARN) mutations on telomere length are likely indirect and may lead to telomere shortening that less perfectly cosegregates with heterozygous mutations. (PMID:26908837)
• PARN increased telomerase RNA component levels by deadenylating telomerase RNA component, thereby limiting its degradation by EXOSC10. (PMID:26950371)
• Pulmonary fibrosis patients with mutations in telomerase reverse transcriptase, telomerase RNA component, regulator of telomere elongation helicase 1 and poly(A)-specific ribonuclease were identified and clinical data were analysed. Genetic mutations in telomere related genes lead to a variety of interstitial lung disease diagnoses that are universally progressive. (PMID:27540018)
• poly(A)-specific ribonuclease (PARN) participates in steps leading to 18S pre-rRNA maturation in human cells (PMID:27899605)
• PARN is a new component of the ribosome biogenesis machinery in human cells. (PMID:28402503)
• PARN polyadenylates the 3’ end of telomerase RNA component (known as TERC or hTR), which serves as the template for telomerase reverse transcriptase-mediated telomere replication. (PMID:28414520)
• provide evidence that PARN can also deadenylate the U6 and RMRP RNAs without affecting their levels (PMID:28760775)
• Results show that PARN deadenylase activity is regulated by the phosphorylated form of Nucleolin. (PMID:29168431)
• PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs). (PMID:29669292)
• Processing of 3’ telomerase RNA occurs in two steps with longer forms first being trimmed by RRP6 and shorter forms then being processed by PARN. (PMID:30575725)
• PARN-mediated shortening is pervasive across most miRNAs and appears to be a conserved mechanism contributing to the 3’ end formation of vertebrate miRNAs. Our findings add miRNAs to the expanding list of noncoding RNAs whose 3’ end formation depends on PARN. (PMID:30591540)
• PARN regulates miRNA levels by stabilizing either mature or precursor miRNAs by removing oligo(A) tails added by the poly(A) polymerase PAPD5, which if remaining recruit the exonuclease DIS3L or DIS3L2 to degrade the miRNA. PARN knockdown destabilizes multiple miRNAs that repress p53 translation, leading to p53 accumulation. (PMID:30770239)
• We find that mature hTR derives from extended precursors but that in PARN-mutant cells hTR maturation kinetically stalls and unprocessed precursors are degraded. Loss of poly(A)polymerase PAPD5 in PARN-mutant cells accelerates hTR maturation and restores hTR processing, indicating that oligoadenylation and deadenylation set rates of hTR maturation (PMID:30930056)
• Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models. (PMID:31273937)
• Intrinsically disordered PARN C-terminal domain is required for PARN nuclear localization in response to DNA damage. (PMID:31387300)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	parn	ENSDARG00000102634
mus_musculus	Parn	ENSMUSG00000022685
rattus_norvegicus	Parn	ENSRNOG00000002912
caenorhabditis_elegans		WBGENE00010734

Paralogs (2): TOE1 (ENSG00000132773), PNLDC1 (ENSG00000146453)

Protein

Protein identifiers

Poly(A)-specific ribonuclease PARN — O95453 (reviewed: O95453)

Alternative names: Deadenylating nuclease, Deadenylation nuclease, Polyadenylate-specific ribonuclease

All UniProt accessions (20): O95453, A0A494BZU6, A0A494BZW7, A0A494C002, A0A494C008, A0A494C0K5, A0A494C0N0, A0A494C0P9, A0A494C0Q2, A0A494C0Q6, A0A494C0W0, A0A494C156, A0A494C1G3, A0A494C1K5, A0A494C1N1, A0A8V8TMN8, F5H1Z4, H3BRK1, H3BT23, H3BVG1

UniProt curated annotations — full annotation on UniProt →

Function. 3’-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3’-end poly(A) tail and the 5’-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3’-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization. Also able to recognize and trim poly(A) tails of microRNAs such as MIR21 and H/ACA box snoRNAs (small nucleolar RNAs) leading to microRNAs degradation or snoRNA increased stability.

Subunit / interactions. Homodimer. Found in a mRNA decay complex with RENT1, RENT2 and RENT3B. Interacts with KHSRP. Interacts with CELF1/CUGBP1. Interacts with ZC3HAV1 in an RNA-independent manner. Interacts with DHX36.

Subcellular location. Nucleus. Cytoplasm. Nucleolus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylation by MAPKAPK2, preventing GADD45A mRNA degradation after genotoxic stress.

Disease relevance. Dyskeratosis congenita, autosomal recessive, 6 (DKCB6) [MIM:616353] A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. The disease is caused by variants affecting the gene represented in this entry. Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 4 (PFBMFT4) [MIM:616371] An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Divalent metal cations. Mg(2+) is the most probable.

Miscellaneous. Non canonical splice junctions.

Similarity. Belongs to the CAF1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O95453-1	1	yes
O95453-2	2
O95453-3	3
O95453-4	4

RefSeq proteins (3): NP_001127949, NP_001229921, NP_002573* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001374	R3H_dom	Domain
IPR006941	RNase_CAF1	Family
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR014789	PolyA-riboNase_RNA-binding	Domain
IPR034042	PARN_R3H	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR036867	R3H_dom_sf	Homologous_superfamily
IPR051181	CAF1_poly(A)_ribonucleases	Family

Pfam: PF04857, PF08675

UniProt features (86 total): helix 20, strand 17, mutagenesis site 16, modified residue 12, turn 7, binding site 4, splice variant 3, sequence variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3CTR	X-RAY DIFFRACTION	2.1
2A1R	X-RAY DIFFRACTION	2.6
2A1S	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95453-F1	81.60	0.62

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 (1): 326 (interaction with poly(a))

Ligand- & substrate-binding residues (4): 28; 30; 292; 382

Post-translational modifications (12): 167, 220, 499, 530, 557, 583, 587, 619, 623, 628, 631, 163

Mutagenesis-validated functional residues (16):

Position	Phenotype
28	loss of function but does not abolish ability to bind rna. induces a decrease in degradation of mrnas containing ares.
28	loss of function in the presence of mg(2+) but not in the presence of mn(2+), zn(2+), co(2+) or cd(2+).
30	loss of function but does not abolish ability to bind rna. induces a decrease in degradation of mrnas containing ares.
30	loss of function in the presence of mg(2+), mn(2+), zn(2+), co(2+) or cd(2+).
31	reduced affinity for poly(a). loss of activity.
34	reduced affinity for poly(a). strongly reduced activity.
113	loss of dimerization. loss of activity.
115	reduced affinity for poly(a). little effect on activity.
123	loss of dimerization. loss of activity.
292	loss of function but does not abolish ability to bind rna.
292	loss of function in the presence of mg(2+) but not in the presence of mn(2+), zn(2+), co(2+) or cd(2+).
326	reduced affinity for poly(a). little effect on activity.
377	loss of activity.
382	loss of function but does not abolish ability to bind rna. induces a decrease in degradation of mrnas containing ares.
382	loss of function in the presence of mg(2+) but not in the presence of mn(2+), zn(2+), co(2+) or cd(2+).
557	strong reduction of phosphorylation by mapkapk2.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-429947	Deadenylation of mRNA
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA

MSigDB gene sets: 445 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, GOBP_SNO_S_RNA_METABOLIC_PROCESS, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (20): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), nuclear-transcribed mRNA poly(A) tail shortening (GO:0000289), box H/ACA sno(s)RNA 3’-end processing (GO:0000495), female gamete generation (GO:0007292), RNA modification (GO:0009451), miRNA catabolic process (GO:0010587), positive regulation of telomere maintenance via telomerase (GO:0032212), poly(A)-dependent snoRNA 3’-end processing (GO:0071051), telomerase RNA stabilization (GO:0090669), lncRNA processing (GO:0180035), regulation of telomerase RNA localization to Cajal body (GO:1904872), priRNA 3’-end processing (GO:1990431), siRNA 3’-end processing (GO:1990432), RNA catabolic process (GO:0006401), mRNA catabolic process (GO:0006402), positive regulation of macromolecule metabolic process (GO:0010604), negative regulation of macromolecule metabolic process (GO:0010605), RNA metabolic process (GO:0016070), regulation of RNA stability (GO:0043487), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

GO Molecular Function (13): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), nuclease activity (GO:0004518), poly(A)-specific ribonuclease activity (GO:0004535), protein kinase binding (GO:0019901), cation binding (GO:0043169), metal ion binding (GO:0046872), telomerase RNA binding (GO:0070034), nucleic acid binding (GO:0003676), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
PERK regulates gene expression	1
Deadenylation-dependent mRNA decay	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA catabolic process	3
cellular anatomical structure	3
nuclear-transcribed mRNA catabolic process	2
sno(s)RNA 3’-end processing	2
RNA metabolic process	2
regulatory ncRNA 3’-end processing	2
macromolecule metabolic process	2
regulation of macromolecule metabolic process	2
binding	2
synapse	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
box H/ACA sno(s)RNA processing	1
gamete generation	1
macromolecule modification	1
miRNA metabolic process	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
RNA stabilization	1
RNA processing	1
regulation of localization	1
telomerase RNA localization to Cajal body	1
nucleic acid catabolic process	1
negative regulation of gene expression	1
mRNA metabolic process	1
positive regulation of metabolic process	1
negative regulation of metabolic process	1
nucleic acid metabolic process	1
regulation of catabolic process	1
post-transcriptional regulation of gene expression	1
regulation of RNA metabolic process	1
regulation of biological quality	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid binding	1
mRNA binding	1
catalytic activity, acting on a nucleic acid	1
3’-5’-RNA exonuclease activity	1
kinase binding	1

Protein interactions and networks

STRING

1268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARN	SYMPK	Q92797	938
PARN	CPEB1	Q9BZB8	930
PARN	KHSRP	Q92945	927
PARN	TENT2	Q6PIY7	905
PARN	PAPOLA	P51003	886
PARN	PAPOLG	Q9BWT3	886
PARN	PAPOLB	Q9NRJ5	886
PARN	NGDN	Q8NEJ9	839
PARN	CNOT6	Q9ULM6	803
PARN	RTEL1	Q9NZ71	799
PARN	CNOT6L	Q96LI5	769
PARN	CTC1	Q2NKJ3	766
PARN	PABPC1	P11940	756
PARN	DKC1	O60832	738
PARN	TINF2	Q9BSI4	723

IntAct

94 interactions, top by confidence:

A	B	Type	Score
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
BYSL	PARN	psi-mi:“MI:0914”(association)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
PARN	BARD1	psi-mi:“MI:0407”(direct interaction)	0.580
BARD1	PARN	psi-mi:“MI:0407”(direct interaction)	0.580
BARD1	PARN	psi-mi:“MI:0914”(association)	0.580
TSR1	PARN	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
TEAD4	PARN	psi-mi:“MI:0914”(association)	0.530
LUC7L2	ZNF593	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
PARN	NCBP1	psi-mi:“MI:0407”(direct interaction)	0.520
CSTF2	PARN	psi-mi:“MI:0914”(association)	0.500
PARN	CSTF2	psi-mi:“MI:0914”(association)	0.500
CSTF2	PARN	psi-mi:“MI:0915”(physical association)	0.500
ZC3HAV1	PARN	psi-mi:“MI:0915”(physical association)	0.400
Zc3hav1	PARN	psi-mi:“MI:0915”(physical association)	0.400
PARN	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TULP3	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
TEAD4	LYPLA1	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350

BioGRID (170): PARN (Reconstituted Complex), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-MS), PARN (Affinity Capture-Western), PARN (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2QC33, A0FKG7, A6H7H7, F1N9S8, O95453, P0C0T1, P42694, P50747, P69341, Q0IIH8, Q0VGM9, Q13572, Q28559, Q4R528, Q5BJZ6, Q5F480, Q5R699, Q5RC51, Q5ZIA0, Q5ZIW7, Q640G7, Q6DDJ3, Q6DFV5, Q6DG88, Q6DJB3, Q6GR37, Q6NYU2, Q6PZ02, Q6PZ03, Q6PZ05, Q7T0P6, Q80UY1, Q80YV4, Q811C2, Q8BGE6, Q8BYN3, Q8C9S8, Q8N4J0, Q8VDG3, Q8WYN0

Diamond homologs: O95453, P69341, Q5RC51, Q7ZU92, Q8VDG3, Q90ZA1, Q17QN2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MAPKAPK2	down-regulates	PARN	phosphorylation
ZC3HAV1	“up-regulates activity”	PARN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
rRNA processing in the nucleus and cytosol	10	21.4×	4e-09
Eukaryotic Translation Initiation	5	20.6×	7e-05
Cap-dependent Translation Initiation	5	20.6×	7e-05
SARS-CoV-1 modulates host translation machinery	5	20.6×	7e-05
rRNA modification in the nucleus and cytosol	8	20.0×	4e-07
rRNA processing	10	19.5×	8e-09
Nonsense-Mediated Decay (NMD)	6	18.6×	2e-05
Eukaryotic Translation Elongation	5	18.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	6	42.1×	1e-06
ribosomal small subunit biogenesis	11	26.1×	2e-10
cytoplasmic translation	7	13.5×	1e-04
rRNA processing	6	8.8×	6e-03
translation	7	7.5×	5e-03
RNA splicing	7	6.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	38
Uncertain significance	455
Likely benign	362
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1338503	NM_002582.4(PARN):c.811dup (p.Ser271fs)	Pathogenic
1342129	NM_002582.4(PARN):c.1624del (p.Gln542fs)	Pathogenic
1394752	NM_002582.4(PARN):c.1624C>T (p.Gln542Ter)	Pathogenic
1418162	NM_002582.4(PARN):c.417_420del (p.Glu139fs)	Pathogenic
1451667	NM_002582.4(PARN):c.1123C>T (p.Gln375Ter)	Pathogenic
1452326	NM_002582.4(PARN):c.382C>T (p.Arg128Ter)	Pathogenic
1455611	NC_000016.9:g.(?14645858)(14711527_?)del	Pathogenic
1695953	NM_002582.4(PARN):c.656G>A (p.Trp219Ter)	Pathogenic
1695961	NM_002582.4(PARN):c.781C>T (p.Gln261Ter)	Pathogenic
180661	NM_002582.4(PARN):c.1148C>T (p.Ala383Val)	Pathogenic
190290	NM_002582.4(PARN):c.863dup (p.Asn288fs)	Pathogenic
190468	NM_002582.4(PARN):c.246-2A>G	Pathogenic
190469	NM_002582.4(PARN):c.529C>T (p.Gln177Ter)	Pathogenic
190470	NM_002582.4(PARN):c.563dup (p.Glu189fs)	Pathogenic
1941438	NM_002582.4(PARN):c.177+1del	Pathogenic
1998806	NM_002582.4(PARN):c.1414C>T (p.Gln472Ter)	Pathogenic
2008012	NM_002582.4(PARN):c.122_123del (p.Ser41fs)	Pathogenic
2029210	NM_002582.4(PARN):c.714del (p.Arg237_Tyr238insTer)	Pathogenic
219121	NM_002582.3(PARN):c.962+295_1263-8706del	Pathogenic
2424488	NC_000016.9:g.(?14711427)(14711527_?)del	Pathogenic
2424489	NC_000016.9:g.(?14645858)(14724045_?)del	Pathogenic
2936222	NM_002582.4(PARN):c.1645C>T (p.Gln549Ter)	Pathogenic
2949321	NM_002582.4(PARN):c.994C>T (p.Gln332Ter)	Pathogenic
3243537	NC_000016.9:g.(?14530574)(14724045_?)del	Pathogenic
3243539	NC_000016.9:g.(?14704491)(14704676_?)del	Pathogenic
3243540	NC_000016.9:g.(?14711427)(14724045_?)del	Pathogenic
3243541	NC_000016.9:g.(?14693741)(14700403_?)del	Pathogenic
3243542	NC_000016.9:g.(?14720953)(14721203_?)del	Pathogenic
3376859	NM_002582.4(PARN):c.634del (p.Lys211_Leu212insTer)	Pathogenic
3747959	NM_002582.4(PARN):c.24dup (p.Lys9Ter)	Pathogenic

SpliceAI

5265 predictions. Top by Δscore:

Variant	Effect	Δscore
16:14482632:TCTTA:T	donor_loss	1.0000
16:14482633:CTTA:C	donor_loss	1.0000
16:14482634:TTA:T	donor_loss	1.0000
16:14482635:TACCT:T	donor_loss	1.0000
16:14482636:A:AC	donor_gain	1.0000
16:14482636:A:C	donor_loss	1.0000
16:14482637:C:CC	donor_gain	1.0000
16:14482637:C:CT	donor_loss	1.0000
16:14482637:CCTA:C	donor_gain	1.0000
16:14482823:GACAG:G	acceptor_gain	1.0000
16:14482824:ACAG:A	acceptor_gain	1.0000
16:14482825:CAG:C	acceptor_gain	1.0000
16:14482825:CAGC:C	acceptor_gain	1.0000
16:14482826:AG:A	acceptor_gain	1.0000
16:14482828:C:CC	acceptor_gain	1.0000
16:14482829:T:A	acceptor_loss	1.0000
16:14552016:CTTA:C	donor_loss	1.0000
16:14552017:TTA:T	donor_loss	1.0000
16:14552018:TA:T	donor_loss	1.0000
16:14552019:A:AC	donor_gain	1.0000
16:14552019:AC:A	donor_gain	1.0000
16:14552020:C:CA	donor_gain	1.0000
16:14552020:CC:C	donor_gain	1.0000
16:14552020:CCA:C	donor_gain	1.0000
16:14552020:CCAA:C	donor_gain	1.0000
16:14552020:CCAAT:C	donor_gain	1.0000
16:14552091:GTTAC:G	acceptor_gain	1.0000
16:14552092:TTAC:T	acceptor_gain	1.0000
16:14552093:TAC:T	acceptor_gain	1.0000
16:14552094:AC:A	acceptor_gain	1.0000

AlphaMissense

4273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:14552053:A:T	V483D	1.000
16:14552059:G:T	A481E	1.000
16:14554104:A:G	W456R	1.000
16:14554104:A:T	W456R	1.000
16:14554130:A:T	V447D	1.000
16:14555674:A:G	L433P	1.000
16:14582213:C:T	G387E	1.000
16:14582214:C:A	G387W	1.000
16:14582225:G:T	A383D	1.000
16:14582226:C:G	A383P	1.000
16:14582227:A:C	D382E	1.000
16:14582227:A:T	D382E	1.000
16:14582228:T:A	D382V	1.000
16:14582228:T:C	D382G	1.000
16:14582228:T:G	D382A	1.000
16:14582229:C:G	D382H	1.000
16:14582244:G:C	H377D	1.000
16:14584400:A:T	L343H	1.000
16:14584768:G:T	A329D	1.000
16:14584769:C:G	A329P	1.000
16:14584776:T:A	K326N	1.000
16:14584776:T:G	K326N	1.000
16:14584777:T:A	K326I	1.000
16:14584778:T:C	K326E	1.000
16:14584784:C:G	D324H	1.000
16:14593344:T:A	D292V	1.000
16:14593344:T:G	D292A	1.000
16:14593355:A:C	N288K	1.000
16:14593355:A:T	N288K	1.000
16:14593358:G:C	H287Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000011039 (16:14542252 C>T), RS1000011524 (16:14597542 A>C), RS1000014610 (16:14499777 G>A), RS1000015669 (16:14569455 C>T), RS1000066560 (16:14569263 G>C,T), RS1000071906 (16:14512006 C>A), RS1000085006 (16:14534477 T>C), RS1000118019 (16:14591785 C>T), RS1000127847 (16:14556875 C>T), RS1000136254 (16:14509844 A>C), RS1000155044 (16:14576819 A>T), RS1000179483 (16:14516212 T>G), RS1000182992 (16:14463924 C>T), RS1000201305 (16:14475330 G>C), RS1000203491 (16:14602049 GCCTC>G)

Disease associations

OMIM: gene MIM:604212 | disease phenotypes: MIM:616353, MIM:616371, MIM:127550, MIM:615067

GenCC curated gene-disease

Disease	Classification	Inheritance
dyskeratosis congenita, autosomal recessive 6	Definitive	Autosomal recessive
pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4	Strong	Autosomal dominant
dyskeratosis congenita	Supportive	Autosomal dominant
Hoyeraal-Hreidarsson syndrome	Supportive	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, Telomere-related, 4	Definitive	SD

Mondo (7): dyskeratosis congenita, autosomal recessive 6 (MONDO:0014600), pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (MONDO:0014612), telomere syndrome (MONDO:0100137), pulmonary fibrosis (MONDO:0002771), dyskeratosis congenita (MONDO:0015780), primary ciliary dyskinesia 20 (MONDO:0014030), Hoyeraal-Hreidarsson syndrome (MONDO:0018045)

Orphanet (3): Idiopathic pulmonary fibrosis (Orphanet:2032), Dyskeratosis congenita (Orphanet:1775), Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000035	Abnormal testis morphology
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000600	Abnormality of the pharynx
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000704	Periodontitis
HP:0000819	Diabetes mellitus
HP:0000939	Osteoporosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001000	Abnormality of skin pigmentation
HP:0001034	Hypermelanotic macule
HP:0001053	Hypopigmented skin patches
HP:0001063	Acrocyanosis
HP:0001231	Abnormal fingernail morphology
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002444_7	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	2.000000e-67
GCST002444_8	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	5.000000e-25
GCST002446_5	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	1.000000e-15
GCST002446_8	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4.000000e-14
GCST002450_10	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2.000000e-12
GCST002702_78	Height	5.000000e-10
GCST003983_38	Male-pattern baldness	8.000000e-09
GCST003993_28	Menarche (age at onset)	6.000000e-12
GCST003994_9	Age at voice drop	7.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0004703	age at menarche
EFO:0007888	age at voice drop

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D011658	Pulmonary Fibrosis	C08.381.483.652; C23.550.355.644
C536068	Hoyeraal Hreidarsson syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3616362 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
bisphenol F	increases expression, decreases methylation, affects cotreatment	2
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol A	decreases methylation	1
bleomycetin	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Arsenic Trioxide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ivermectin	increases expression	1
Methapyrilene	decreases methylation	1
Potassium Dichromate	decreases expression	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Vitamin E	increases expression	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
CHEMBL3619398	Binding	Inhibition of PARN (unknown origin)	Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

221 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
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT04638517	PHASE2	TERMINATED	The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With 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
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