DKC1

Summary

DKC1 (dyskerin pseudouridine synthase 1, HGNC:2890) is a protein-coding gene on chromosome Xq28, encoding H/ACA ribonucleoprotein complex subunit DKC1 (O60832). Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. It is a common-essential gene (DepMap: required in 97.0% of cancer cell lines).

This gene functions in two distinct complexes. It plays an active role in telomerase stabilization and maintenance, as well as recognition of snoRNAs containing H/ACA sequences which provides stability during biogenesis and assembly into H/ACA small nucleolar RNA ribonucleoproteins (snoRNPs). This gene is highly conserved and widely expressed, and may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion. Mutations have been associated with X-linked dyskeratosis congenita. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1736 — RefSeq curated summary.

At a glance

• Gene–disease (curated): DKC1-related disorder (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 645 total — 19 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 123
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001363

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2890
Approved symbol	DKC1
Name	dyskerin pseudouridine synthase 1
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	XAP101, dyskerin, NAP57, NOLA4, Cbf5
Ensembl gene	ENSG00000130826
Ensembl biotype	protein_coding
OMIM	300126
Entrez	1736

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 15 retained_intron, 12 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000369550, ENST00000412124, ENST00000413910, ENST00000426673, ENST00000437719, ENST00000473552, ENST00000475423, ENST00000475966, ENST00000481062, ENST00000484317, ENST00000492372, ENST00000620277, ENST00000696575, ENST00000696576, ENST00000696577, ENST00000696578, ENST00000696579, ENST00000696580, ENST00000696581, ENST00000696582, ENST00000696583, ENST00000696584, ENST00000696585, ENST00000696586, ENST00000696587, ENST00000696588, ENST00000696589, ENST00000696590, ENST00000696591, ENST00000696592, ENST00000696627, ENST00000696628, ENST00000939406, ENST00000939407, ENST00000939408, ENST00000953351

RefSeq mRNA: 3 — MANE Select: NM_001363 NM_001142463, NM_001288747, NM_001363

CCDS: CCDS14761, CCDS94705

Canonical transcript exons

ENST00000369550 — 15 exons

Exon	Start	End
ENSE00001635997	154769167	154769310
ENSE00003499854	154775195	154775273
ENSE00003648726	154776187	154776324
ENSE00003967619	154764899	154764966
ENSE00003967621	154768302	154768432
ENSE00003967622	154767256	154767382
ENSE00003967623	154765444	154765530
ENSE00003967624	154766997	154767061
ENSE00003967625	154765907	154765998
ENSE00003967626	154766216	154766400
ENSE00003967766	154762864	154762981
ENSE00003967780	154776799	154777689
ENSE00003967884	154770759	154770879
ENSE00003967892	154773131	154773249
ENSE00003967893	154774602	154774705

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.8019 / max 576.1547, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198205	36.1736	1818
198206	14.5891	1754
198203	2.5223	1183
198204	2.5169	1212

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.78	gold quality
sural nerve	UBERON:0015488	96.66	gold quality
gingival epithelium	UBERON:0001949	96.59	gold quality
tongue squamous epithelium	UBERON:0006919	96.09	gold quality
hair follicle	UBERON:0002073	96.02	gold quality
tibia	UBERON:0000979	95.90	gold quality
squamous epithelium	UBERON:0006914	95.83	gold quality
tendon of biceps brachii	UBERON:0008188	95.83	gold quality
oocyte	CL:0000023	95.81	gold quality
gingiva	UBERON:0001828	95.80	gold quality
esophagus squamous epithelium	UBERON:0006920	95.63	gold quality
pancreatic ductal cell	CL:0002079	95.10	gold quality
tendon	UBERON:0000043	94.91	gold quality
epithelium of esophagus	UBERON:0001976	94.88	gold quality
calcaneal tendon	UBERON:0003701	94.65	gold quality
epithelium of nasopharynx	UBERON:0001951	94.31	gold quality
cartilage tissue	UBERON:0002418	94.28	gold quality
body of pancreas	UBERON:0001150	94.09	gold quality
cervix squamous epithelium	UBERON:0006922	94.05	gold quality
esophagus mucosa	UBERON:0002469	93.96	gold quality
islet of Langerhans	UBERON:0000006	93.94	gold quality
pancreas	UBERON:0001264	93.91	gold quality
palpebral conjunctiva	UBERON:0001812	93.59	gold quality
rectum	UBERON:0001052	93.51	gold quality
tonsil	UBERON:0002372	93.48	gold quality
bone marrow	UBERON:0002371	93.46	gold quality
skin of abdomen	UBERON:0001416	93.31	gold quality
lymph node	UBERON:0000029	93.18	gold quality
vermiform appendix	UBERON:0001154	93.05	gold quality
cervix epithelium	UBERON:0004801	92.94	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SP1

miRNA regulators (miRDB)

25 targeting DKC1, 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-3134	100.00	66.43	777
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-562	97.66	65.63	698
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-621	96.76	66.89	371

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 97.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Characterizes the mouse DKC1 ortholog. (PMID:10903840)
• TEP1, hTR, hsp90, p23, and dyskerin remained at high and unchanged levels throughout up- or down regulation of telomerase activity. (PMID:12135483)
• the human TruB family includes at least three members: DKC1 (previously identified), TRUB1 and TRUB2. (PMID:12736709)
• Review. DKC1 encodes dyskerin, a protein component of small nucleolar ribonucleoprotein particles. Dyskerin & TERC closely associate with each other in the telomerase complex. DKC1 deficiency causes X-linked dyskeratosis congenita. (PMID:15613268)
• specific defect in IRES (internal ribosome entry site)-dependent translation in X-linked dyskeratosis congenita cells; defect results in impaired translation of mRNAs containing IRES elements, including those encoding p27Kip1), Bcl-xL and XIAP (PMID:16690864)
• protein composition of catalytically active telomerase; mass spectrometric sequencing of the components & molecular size determination indicate an enzyme composition of two molecules each of telomerase reverse transcriptase, telomerase RNA & dyskerin (PMID:17395830)
• THe first case of X-linked DC in Malaysia and a novel mutation in the DKC1 gene are described. (PMID:17417794)
• mutations in the telomerase complex and their connections with dyskeratosis congenita and bone marrow failures [review] (PMID:17625368)
• These data indicate that DKC1 is a direct and conserved transcriptional target of c-MYC, and suggest a biologic basis for DKC1 overexpression in neoplasia. (PMID:17822678)
• These data demonstrate that this domain of dyskerin plays an important role in telomerase maintenance following cell insults such as cisplatin treatment, and in telomerase-defective cells in patients with X-linked dyskeratosis congenita. (PMID:18057229)
• Significantly higher DKC1 mRNA is associated with colorectal cancer. (PMID:18607840)
• An intronic splice site mutation in DKC1 was found in an infant with Hoyeraal-Hreidarsson syndrome. (PMID:18627054)
• a 2 bp inversion in exon 3: NM_001363:c.166_167invCT (Leu56Ser) mutation in DKC1 in dyskeratosis congenita identified in a Russian family (PMID:18802941)
• Results indicated that, beside its effect on ribosome biogenesis, the levels of dyskerin in cancer cells modulate telomerase activity through the regulation of TERC levels, independently of TERT expression. (PMID:18936525)
• Impaired interaction between NAP57 and SHQ1 is a molecular basis for dyskeratosis congenita. (PMID:19734544)
• DKC1 upregulation in prostate cancers is common and likely to be necessary for extensive tumour growth. (PMID:19755982)
• Dyskerin mutations associated with X-linked dyskeratosis congenita (DC) resulted in significant impairment of the dyskerin- telomerase RNA (TR) interaction, whereas mutations in TR associated with autosomal dominant DC did not affect the interaction. (PMID:19835419)
• Analyzed was genomic DNA isolated from peripheral lymphocytes of 17 individuals affected with dyskeratosis congenita. Two novel mutations were discovered. (PMID:19879169)
• Effects of dyskeratosis congenita mutations in dyskerin on assembly of H/ACA pre-RNPs (PMID:20008900)
• Bisulfite sequencing revealed that only FancB and DKC1 showed no methylation in normal patients, yet the presence of promoter hypermethylation in HNSCC patients. (PMID:20332657)
• Impairment of dyskerin function causes p53 inactivation due to a defect in p53 mRNA translation. Reduction of dyskerin causes a decrease of p53 mRNA translation and protein levels in human breast cancer cells and mammary epithelial progenitor cells. (PMID:20501855)
• intact dyskerin levels, in the absence of coding mutations, are critical for telomerase RNA stability and for in vivo telomere maintenance. (PMID:21415081)
• Data reinforce the notion that loss and gain of dyskerin function may play important roles in tumorigenesis. (PMID:21480387)
• a recurrent mutation c.1058 C>T (p. A353V) in the DKC1 responsible for dyskeratosis congenita in a Chinese family was identified. (PMID:21601430)
• The role of dyskerin in tumorigenesis does not correlate with its function within the telomerase complex. Dyskerin is often overexpressed in oral squamous cell carcinoma, and correlates with active cell proliferation. (PMID:21674675)
• A genetic analysis was performed and a new missense mutation S356P, hemizygous, was identified in the DKC1 gene in two dyskeratosis congenita patients. (PMID:21736606)
• suggests that DKC1 nucleolar and cytoplasmic functions might cumulatively account for the plethora of manifestations displayed by this syndrome (PMID:21820037)
• purified telomerase holoenzyme complexes from different X-linked dyskeratosis congenita (X-DC) cells have normal catalytic activity; data confirm that dyskerin promotes telomerase RNA (TER) stability in vivo, endorsing the development of TER supplementation strategies for the treatment of X-DC (PMID:22058290)
• rRNA pseudouridylation defects resulted from a deficient pseudouridylate synthetase affect ribosomal ligand binding and translational fidelity from yeast to human cells. (PMID:22099312)
• Two novel mutations (p.His68Arg and p.Lys390del) have been found in DKC1 genes of Spanish patients with dyskeratosis congenita. (PMID:22664374)
• Dyskerin overexpression in human hepatocellular carcinoma is associated with advanced clinical stage and poor patient prognosis. (PMID:22912812)
• SMUG1 is a DKC1 interaction partner that contributes to rRNA quality control, partly by regulating 5-hydroxymethyluridine levels. (PMID:23246433)
• We describe an African American family with Hoyeraal-Hreidarrson syndrome (HHS) in which 2 TERT mutations (causing P530L and A880T amino acid changes) and two in the DKC1 variants (G486R and A487A) were segregating. (PMID:23335200)
• Direct DKC1 gene mutations were not a frequent event in human lung, breast or colon tumourigenesis. (PMID:23348390)
• Results show that dyskerin stability is regulated by SUMOylation and that mutations altering dyskerin SUMOylation can lead to defects in telomere maintenance that are characteristics of dyskeratosis congenita. (PMID:23660516)
• that females with heterozygous DKC1 mutations may be at increased risk for developing penetrant telomere phenotypes that, at times, may be associated with clinical morbidity. (PMID:23946118)
• 3 novel alternative splice isoforms of DKC1 derived from human X-linked dyskeratosis congenita 1 have been identified. (PMID:24219293)
• dyskerin is a highly dynamic protein throughout the cell cycle and increases the repertoire of fundamental cellular processes that are disrupted by absence of its normal function. (PMID:24303026)
• DKC1 variant represents the third telomere-related gene identified as a genetic cause of FIP. (PMID:24504062)
• Using human U2OS osteosarcoma cells, the study shows that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. (PMID:24690175)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dkc1	ENSDARG00000016484
mus_musculus	Dkc1	ENSMUSG00000031403
rattus_norvegicus	Dkc1	ENSRNOG00000074843
drosophila_melanogaster	Nop60B	FBGN0259937
caenorhabditis_elegans		WBGENE00010478

Protein

Protein identifiers

H/ACA ribonucleoprotein complex subunit DKC1 — O60832 (reviewed: O60832)

Alternative names: CBF5 homolog, Dyskerin, Nopp140-associated protein of 57 kDa, Nucleolar protein NAP57, Nucleolar protein family A member 4, snoRNP protein DKC1

All UniProt accessions (14): O60832, A0A8Q3SIS9, A0A8Q3SIX2, A0A8Q3SIY6, A0A8Q3SJE8, A0A8Q3WLC8, A0A8Q3WLD1, A0A8Q3WLE4, A0A8Q3WLE5, A0A8Q3WLG7, A0A8Q3WLW8, A0A8V8TKY9, C9IYT0, H7C2Q2

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine (‘psi’) residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance. Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme. Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression.

Subunit / interactions. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. During assembly, the complex contains NAF1 instead of GAR1/NOLA1. The complex also interacts with TERC, which contains a 3’-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. Interacts with SHQ1; this interaction may lead to the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA. Interacts with HMBOX1. Interacts with DHX36.

Subcellular location. Nucleus. Nucleolus. Cajal body Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Disease relevance. Dyskeratosis congenita, X-linked (DKCX) [MIM:305000] A rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. 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. Reduced rRNA pseudouridine levels in cells from patients. Hoyeraal-Hreidarsson syndrome (HHS) [MIM:305000] A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency. The disease is caused by variants affecting the gene represented in this entry. Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 (CHINE1) [MIM:301108] An X-linked dominant disorder characterized by infantile onset of steroid-resistant nephrotic syndrome, cataracts, sensorineural deafness, and enterocolitis. Males are more severely affected than females, and death occurs in early childhood. Affected females develop early-onset hearing impairment, early-onset cataracts, but only rarely have nephrotic syndrome. They do not have enterocolitis. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the pseudouridine synthase TruB family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60832-1	1	yes
O60832-2	3

RefSeq proteins (3): NP_001135935, NP_001275676, NP_001354* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002478	PUA	Domain
IPR002501	PsdUridine_synth_N	Domain
IPR004521	Uncharacterised_CHP00451	Domain
IPR004802	tRNA_PsdUridine_synth_B_fam	Family
IPR012960	Dyskerin-like	Domain
IPR015947	PUA-like_sf	Homologous_superfamily
IPR020103	PsdUridine_synth_cat_dom_sf	Homologous_superfamily
IPR032819	TruB_C	Domain
IPR036974	PUA_sf	Homologous_superfamily

Pfam: PF01472, PF01509, PF08068, PF16198

Catalyzed reactions (Rhea), 1 shown:

• uridine in 5S rRNA = pseudouridine in 5S rRNA (RHEA:47036)

UniProt features (94 total): sequence variant 26, strand 19, helix 12, modified residue 10, cross-link 10, turn 4, region of interest 3, sequence conflict 3, initiator methionine 1, chain 1, domain 1, splice variant 1, mutagenesis site 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8OUE	ELECTRON MICROSCOPY	2.7
9QB2	ELECTRON MICROSCOPY	3
8OUF	ELECTRON MICROSCOPY	3.1
7TRC	ELECTRON MICROSCOPY	3.3
7BGB	ELECTRON MICROSCOPY	3.4
9QB3	ELECTRON MICROSCOPY	3.9
7V9A	ELECTRON MICROSCOPY	3.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60832-F1	79.74	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): 125 (nucleophile)

Post-translational modifications (20): 387, 451, 453, 455, 458, 485, 494, 513, 20, 39, 43, 191, 394, 413, 413, 424, 433, 467, 2, 21

Mutagenesis-validated functional residues (1):

Position	Phenotype
353	increases interaction with shq1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-6790901	rRNA modification in the nucleus and cytosol

MSigDB gene sets: 550 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GNF2_MSH2, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, PID_TELOMERASE_PATHWAY, GOBP_SNO_S_RNA_METABOLIC_PROCESS, MORF_HDAC1, MORF_UBE2N, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION

GO Biological Process (19): enzyme-directed rRNA pseudouridine synthesis (GO:0000455), box H/ACA sno(s)RNA 3’-end processing (GO:0000495), rRNA processing (GO:0006364), RNA processing (GO:0006396), telomere maintenance via telomerase (GO:0007004), rRNA pseudouridine synthesis (GO:0031118), snRNA pseudouridine synthesis (GO:0031120), positive regulation of telomere maintenance via telomerase (GO:0032212), scaRNA localization to Cajal body (GO:0090666), telomerase RNA stabilization (GO:0090669), protein localization to Cajal body (GO:1904867), regulation of telomerase RNA localization to Cajal body (GO:1904872), positive regulation of telomerase RNA localization to Cajal body (GO:1904874), telomerase holoenzyme complex assembly (GO:1905323), mRNA pseudouridine synthesis (GO:1990481), pseudouridine synthesis (GO:0001522), RNA modification (GO:0009451), box H/ACA sno(s)RNA metabolic process (GO:0033979), ribosome biogenesis (GO:0042254)

GO Molecular Function (7): telomerase activity (GO:0003720), RNA binding (GO:0003723), pseudouridine synthase activity (GO:0009982), box H/ACA snoRNA binding (GO:0034513), telomerase RNA binding (GO:0070034), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (11): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), nucleolus (GO:0005730), cytoplasm (GO:0005737), box H/ACA snoRNP complex (GO:0031429), box H/ACA scaRNP complex (GO:0072589), box H/ACA telomerase RNP complex (GO:0090661), Cajal body (GO:0015030), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Extension of Telomeres	1
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	4
pseudouridine synthesis	3
cellular anatomical structure	3
catalytic complex	3
box H/ACA RNP complex	3
telomerase RNA localization to Cajal body	2
nucleolus	2
nuclear lumen	2
rRNA pseudouridine synthesis	1
sno(s)RNA 3’-end processing	1
box H/ACA sno(s)RNA processing	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
rRNA modification	1
snRNA modification	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 localization to Cajal body	1
RNA stabilization	1
protein localization to nuclear body	1
regulation of localization	1
positive regulation of biological process	1
regulation of telomerase RNA localization to Cajal body	1
protein-RNA complex assembly	1
mRNA modification	1
RNA modification	1
RNA metabolic process	1
macromolecule modification	1
sno(s)RNA metabolic process	1
ribonucleoprotein complex biogenesis	1

Protein interactions and networks

STRING

3992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DKC1	NHP2	Q9NX24	999
DKC1	TERT	O14746	999
DKC1	WRAP53	Q9BUR4	999
DKC1	NOP10	Q9NPE3	999
DKC1	GAR1	Q9NY12	983
DKC1	FBL	P22087	973
DKC1	SHQ1	Q6PI26	960
DKC1	RUVBL1	P82276	952
DKC1	RUVBL2	Q9Y230	949
DKC1	TINF2	Q9BSI4	944
DKC1	NOP58	Q9Y2X3	917
DKC1	PUS1	Q9Y606	911
DKC1	NOLC1	Q14978	910
DKC1	TERF1	P54274	885
DKC1	SNU13	P55769	874

IntAct

331 interactions, top by confidence:

A	B	Type	Score
WRAP53	DKC1	psi-mi:“MI:0914”(association)	0.830
RUVBL1	DKC1	psi-mi:“MI:0914”(association)	0.820
RUVBL1	DKC1	psi-mi:“MI:0407”(direct interaction)	0.820
DKC1	RUVBL1	psi-mi:“MI:0915”(physical association)	0.820
RUVBL2	DKC1	psi-mi:“MI:0914”(association)	0.810
GAR1	DKC1	psi-mi:“MI:0914”(association)	0.790
DKC1	TERT	psi-mi:“MI:0915”(physical association)	0.750
DKC1	TERT	psi-mi:“MI:0914”(association)	0.750
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
NHP2	DKC1	psi-mi:“MI:0914”(association)	0.730
DKC1	SHQ1	psi-mi:“MI:0915”(physical association)	0.670
DDX21	DKC1	psi-mi:“MI:0914”(association)	0.640
RUVBL1	TERT	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530

BioGRID (559): DKC1 (Affinity Capture-RNA), DKC1 (Affinity Capture-RNA), DKC1 (Affinity Capture-RNA), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ5, A6QPY8, B5KFL3, F1Q749, F1RRT2, F8RP11, O43100, O43102, O60832, O88600, P02600, P02606, P05977, P08590, P09541, P09542, P12829, P16409, P17209, P34932, P85100, Q12906, Q15147, Q28BT8, Q2TFN9, Q4I665, Q4WJM6, Q503Y7, Q5B5W1, Q5R495, Q5R887, Q5RDM4, Q5ZJH9, Q5ZLF0, Q5ZLN5, Q61316, Q66T82, Q6GL57, Q6P4K8, Q6P848

Diamond homologs: A0KTZ8, A1AG71, A1K7B7, A1RTL7, A1S464, A1U5Z8, A3MS77, A3N007, A4G0N3, A4IME0, A4VPN8, A4WEY1, A4WH37, A4XYD8, A5F928, A5W985, A6TEI5, A6UWC6, A6VHV2, A7MZI3, A8A4Y2, A8AQ55, A8FDD4, A9A8X7, A9KBM3, A9N8V4, B0KHX6, B0R686, B1L793, B1YA64, B5FA81, B6ENE4, B6YSP4, B7VJH5, C3LSQ0, C4K3E8, C4L8X2, C5A255, F1Q749, G0SGK0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DKC1	“up-regulates activity”	TERT	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 200 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
Telomere Extension By Telomerase	8	27.5×	9e-09
Extension of Telomeres	5	22.6×	6e-05
Peptide chain elongation	18	17.2×	1e-15
Viral mRNA Translation	18	17.2×	1e-15
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	18	17.0×	1e-15
Selenocysteine synthesis	18	16.3×	2e-15
Eukaryotic Translation Termination	18	16.3×	2e-15
Formation of a pool of free 40S subunits	19	16.0×	9e-16

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance via telomerase	5	21.1×	4e-04
cytoplasmic translation	19	20.2×	7e-17
spliceosomal complex assembly	5	17.3×	8e-04
ribosomal large subunit biogenesis	6	15.3×	3e-04
regulation of signal transduction by p53 class mediator	6	13.2×	5e-04
translation	22	13.0×	9e-16
rRNA processing	15	12.2×	4e-10
negative regulation of viral genome replication	5	10.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	12
Uncertain significance	155
Likely benign	268
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11582	NM_001363.5(DKC1):c.106T>G (p.Phe36Val)	Pathogenic
11584	NM_001363.5(DKC1):c.119C>G (p.Pro40Arg)	Pathogenic
11585	NM_001363.5(DKC1):c.214_215delinsTA (p.Leu72Tyr)	Pathogenic
11586	NM_001363.5(DKC1):c.1205G>A (p.Gly402Glu)	Pathogenic
11587	NM_001363.5(DKC1):c.1058C>T (p.Ala353Val)	Pathogenic
11588	NC_000023.11:g.(154776372_154776374)_(154778317_154778319)del	Pathogenic
11590	NM_001363.5(DKC1):c.16+592C>G	Pathogenic
11591	NM_001363.5(DKC1):c.146C>T (p.Thr49Met)	Pathogenic
11593	NM_001363.5(DKC1):c.113T>C (p.Ile38Thr)	Pathogenic
11594	NM_001363.5(DKC1):c.91C>A (p.Gln31Lys)	Pathogenic
11596	NM_001363.5(DKC1):c.1259+1G>A	Pathogenic
1782258	NM_001363.5(DKC1):c.189T>G (p.Asn63Lys)	Pathogenic
235576	NM_001363.5(DKC1):c.1345C>G (p.Arg449Gly)	Pathogenic
2506511	NM_001363.5(DKC1):c.616G>A (p.Glu206Lys)	Pathogenic
2828899	NM_001363.5(DKC1):c.5_7del (p.Ala2del)	Pathogenic
38936	NM_001363.5(DKC1):c.1156G>A (p.Ala386Thr)	Pathogenic
446380	NM_001363.5(DKC1):c.203A>G (p.His68Arg)	Pathogenic
4725422	NM_001363.5(DKC1):c.969T>A (p.Tyr323Ter)	Pathogenic
564941	GRCh37/hg19 Xq28(chrX:153749360-155233731)x3	Pathogenic
11583	NM_001363.5(DKC1):c.109_111del (p.Leu37del)	Likely pathogenic
1343818	NM_001363.5(DKC1):c.204C>G (p.His68Gln)	Likely pathogenic
2579111	NM_001363.5(DKC1):c.197C>T (p.Thr66Ile)	Likely pathogenic
2664154	NM_001363.5(DKC1):c.114C>G (p.Ile38Met)	Likely pathogenic
2674846	NM_001363.5(DKC1):c.964C>T (p.Arg322Ter)	Likely pathogenic
38942	NM_001363.5(DKC1):c.1226C>T (p.Pro409Leu)	Likely pathogenic
38957	NM_001363.5(DKC1):c.949C>T (p.Leu317Phe)	Likely pathogenic
427887	NM_001363.5(DKC1):c.1054A>G (p.Thr352Ala)	Likely pathogenic
434943	NM_001363.5(DKC1):c.1255T>A (p.Tyr419Asn)	Likely pathogenic
574416	NM_001363.5(DKC1):c.149C>A (p.Ser50Tyr)	Likely pathogenic
916631	NM_001363.5(DKC1):c.1195G>C (p.Asp399His)	Likely pathogenic

SpliceAI

2307 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154762982:G:GC	donor_loss	1.0000
X:154764897:A:AG	acceptor_gain	1.0000
X:154764898:G:GA	acceptor_gain	1.0000
X:154764898:GT:G	acceptor_gain	1.0000
X:154764898:GTA:G	acceptor_gain	1.0000
X:154764898:GTAA:G	acceptor_gain	1.0000
X:154764898:GTAAT:G	acceptor_gain	1.0000
X:154764963:AGCCG:A	donor_loss	1.0000
X:154764964:GCC:G	donor_gain	1.0000
X:154764964:GCCGT:G	donor_loss	1.0000
X:154764965:CCG:C	donor_loss	1.0000
X:154764966:CG:C	donor_loss	1.0000
X:154764967:G:GG	donor_gain	1.0000
X:154764967:GTG:G	donor_loss	1.0000
X:154764971:GTA:G	donor_gain	1.0000
X:154765439:C:CA	acceptor_gain	1.0000
X:154765902:TGTA:T	acceptor_loss	1.0000
X:154765903:GTAG:G	acceptor_loss	1.0000
X:154765904:TA:T	acceptor_loss	1.0000
X:154765905:A:AG	acceptor_gain	1.0000
X:154765906:G:GA	acceptor_gain	1.0000
X:154765906:GA:G	acceptor_gain	1.0000
X:154765906:GAA:G	acceptor_gain	1.0000
X:154765906:GAAT:G	acceptor_gain	1.0000
X:154765906:GAATT:G	acceptor_gain	1.0000
X:154765997:AGGT:A	donor_loss	1.0000
X:154765999:GTAA:G	donor_loss	1.0000
X:154766000:T:G	donor_loss	1.0000
X:154766209:A:AG	acceptor_gain	1.0000
X:154766210:T:G	acceptor_gain	1.0000

AlphaMissense

3363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154766221:G:A	G90D	1.000
X:154766233:T:A	L94H	1.000
X:154766233:T:C	L94P	1.000
X:154766238:A:C	K96Q	1.000
X:154766238:A:G	K96E	1.000
X:154766240:G:C	K96N	1.000
X:154766240:G:T	K96N	1.000
X:154766249:C:A	N99K	1.000
X:154766249:C:G	N99K	1.000
X:154766250:C:T	P100S	1.000
X:154766251:C:A	P100H	1.000
X:154766254:C:A	S101Y	1.000
X:154766254:C:T	S101F	1.000
X:154766257:C:A	S102Y	1.000
X:154766257:C:T	S102F	1.000
X:154766259:C:A	H103N	1.000
X:154766259:C:G	H103D	1.000
X:154766259:C:T	H103Y	1.000
X:154766260:A:G	H103R	1.000
X:154766261:T:A	H103Q	1.000
X:154766261:T:G	H103Q	1.000
X:154766262:G:A	E104K	1.000
X:154766263:A:T	E104V	1.000
X:154766264:G:C	E104D	1.000
X:154766264:G:T	E104D	1.000
X:154766271:G:C	A107P	1.000
X:154766274:T:A	W108R	1.000
X:154766274:T:C	W108R	1.000
X:154766290:T:C	L113P	1.000
X:154766307:G:A	G119R	1.000

dbSNP variants (sampled 300 via entrez): RS1000211222 (X:154775440 T>A), RS1000801126 (X:154761680 G>A,T), RS1000854943 (X:154760998 G>C), RS1001836492 (X:154773959 T>C), RS1001887364 (X:154773864 C>T), RS1002559487 (X:154769217 T>C), RS1003097480 (X:154762265 T>C), RS1003565107 (X:154771563 A>G), RS1003691268 (X:154763601 T>C), RS1004148596 (X:154763339 G>A), RS1004417248 (X:154763892 C>T), RS1004468190 (X:154763654 A>G), RS1004696356 (X:154771944 A>T), RS1005963137 (X:154769684 T>C), RS1006091882 (X:154762622 C>A,T)

Disease associations

OMIM: gene MIM:300126 | disease phenotypes: MIM:127550, MIM:305000, MIM:301108, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
dyskeratosis congenita, X-linked	Definitive	X-linked
DKC1-related disorder	Strong	X-linked
dyskeratosis congenita	Supportive	Autosomal dominant
Hoyeraal-Hreidarsson syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
DKC1-related disorder	Definitive	XL
dyskeratosis congenita, X-linked	Definitive	XL

Mondo (7): dyskeratosis congenita (MONDO:0015780), DKC1-related disorder (MONDO:0100152), dyskeratosis congenita, X-linked (MONDO:0010584), Hoyeraal-Hreidarsson syndrome (MONDO:0018045), cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 (MONDO:0958178), pulmonary fibrosis (MONDO:0002771), isolated cerebellar hypoplasia/agenesis (MONDO:0008939)

Orphanet (4): Dyskeratosis congenita (Orphanet:1775), Hoyeraal-Hreidarsson syndrome (Orphanet:3322), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246)

HPO phenotypes

123 total (30 of 123 shown, HPO-id order):

HPO	Term
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000486	Strabismus
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000568	Microphthalmia
HP:0000600	Abnormality of the pharynx
HP:0000648	Optic atrophy
HP:0000653	Sparse eyelashes
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000704	Periodontitis
HP:0000819	Diabetes mellitus
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

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
C562568	Cerebellar Hypoplasia (supp.)
C536068	Hoyeraal Hreidarsson syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724912 (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

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

pChembl	Type	Value	Unit	Molecule
8.22	Kd	6	nM	MOLIBRESIB
8.00	IC50	10	nM	MOLIBRESIB
5.50	Kd	3139	nM	CHEMBL3752910
5.50	ED50	3139	nM	CHEMBL3752910
5.22	Kd	5989	nM	CHEMBL5653589
5.22	ED50	5989	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 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	2179215: Binding affinity against DKC1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0060	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148242: Binding affinity to human DKC1 incubated for 45 mins by Kinobead based pull down assay	kd	3.1388	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148242: Binding affinity to human DKC1 incubated for 45 mins by Kinobead based pull down assay	kd	5.9895	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
cobaltous chloride	decreases expression	2
nickel sulfate	decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	increases expression	2
Mustard Gas	decreases expression, increases phosphorylation	2
Plant Extracts	affects cotreatment, increases expression, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
methylselenic acid	decreases expression	1
decabromobiphenyl ether	increases expression	1
methylparaben	increases expression	1
afimoxifene	decreases reaction, increases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nivalenol	increases expression	1
bicalutamide	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651284	Binding	Binding affinity to human DKC1 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

Cellosaurus cell lines

15 cell lines: 7 induced pluripotent stem cell, 5 transformed cell line, 3 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0G94	GM01786	Finite cell line	Female
CVCL_0G95	GM01787	Finite cell line	Female
CVCL_0H19	M3F-1	Induced pluripotent stem cell	Female
CVCL_0H20	M3F-2	Induced pluripotent stem cell	Female
CVCL_7336	GM01774	Finite cell line	Male
CVCL_AB29	GM03193	Transformed cell line	Male
CVCL_AB30	GM03194	Transformed cell line	Male
CVCL_AB31	GM03195	Transformed cell line	Male
CVCL_AB33	GM03650	Transformed cell line	Female
CVCL_D515	GM01775	Transformed cell line	Male

Clinical trials (associated diseases)

220 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
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
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
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)