pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2

Summary

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2 (MONDO:0013879) is a disease with 1 cohort gene and 237 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, romiplostim, and eltrombopag.

At a glance

• Cohort genes: 1
• ClinVar variants: 20
• Clinical trials: 237

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2
Mondo ID	MONDO:0013879
OMIM	614743
UMLS	C3553622
MedGen	766536
GARD	0024960
Is cancer (heuristic)	no

Also known as: aplastic anaemia · aplastic anemia · PFBMFT2 · pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2 · pulmonary fibrosis and/or bone marrow failure, Telomere-related, type 2

Data availability: 20 ClinVar variants · 15 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › lung disorder › interstitial lung disease › pulmonary fibrosis › pulmonary fibrosis and/or bone marrow failure, telomere-related › pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2

Related subtypes (8): pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, pulmonary fibrosis and/or bone marrow failure, telomere-related, 5, pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8, pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

20 retrieved; paginated sample, class counts are floors:

9 pathogenic, 4 uncertain significance, 2 benign/likely benign, 2 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
36953	NR_001566.3(TERC):n.212C>G	LOC110806306	Pathogenic	no assertion criteria provided
39282	NR_001566.3(TERC):n.143G>A	LOC110806306	Pathogenic	no assertion criteria provided
446376	NR_001566.3(TERC):n.69_74dup	LOC110806306	Pathogenic	criteria provided, single submitter
446377	NR_001566.3(TERC):n.107G>T	LOC110806306	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446378	NR_001566.3(TERC):n.118_121GCGG[1]	LOC110806306	Pathogenic	criteria provided, single submitter
7322	NR_001566.3(TERC):n.204C>G	LOC110806306	Pathogenic	no assertion criteria provided
7324	NR_001566.3(TERC):n.72C>G	LOC110806306	Pathogenic	no assertion criteria provided
7325	NR_001566.3(TERC):n.108_111delCTGA	LOC110806306	Pathogenic	criteria provided, single submitter
7327	NR_001566.3(TERC):n.98G>A	LOC110806306	Pathogenic	no assertion criteria provided
7328	NR_001566.3(TERC):n.325G>T	LOC110806306	Pathogenic	no assertion criteria provided
446379	NC_000003.12:g.169764653_169764654delinsTT	TERC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024213	NR_001566.3(TERC):n.301A>T	LOC110806306	Likely pathogenic	criteria provided, single submitter
7326	NR_001566.3(TERC):n.116C>T	LOC110806306	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
983511	NR_001566.3(TERC):n.95G>C	LOC110806306	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
39292	NR_001566.3(TERC):n.35C>T	LOC110806306	Uncertain significance	criteria provided, multiple submitters, no conflicts
39293	NR_001566.3(TERC):n.37A>G	LOC110806306	Uncertain significance	criteria provided, multiple submitters, no conflicts
4845384	NR_001566.3(TERC):n.212C>T	LOC110806306	Uncertain significance	criteria provided, single submitter
619284	NR_001566.3(TERC):n.36C>T	LOC110806306	Uncertain significance	criteria provided, multiple submitters, no conflicts
39286	NR_001566.3(TERC):n.228G>A	LOC110806306	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
7323	NR_001566.3(TERC):n.58G>A	LOC110806306	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERC	Orphanet:1775	Dyskeratosis congenita
TERC	Orphanet:2032	Idiopathic pulmonary fibrosis
TERC	Orphanet:88	Idiopathic aplastic anemia

Cohort genes → proteins

1 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERC	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERC	0

Structural data

PDB: 0 · AlphaFold-only: 0 · No structure: 1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TERC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TERC

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TERC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 237.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	83
Not specified	76
PHASE1/PHASE2	27
PHASE4	17
PHASE1	13
PHASE3	10
PHASE2/PHASE3	7
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06424639	PHASE4	NOT_YET_RECRUITING	Luspatercept Plus CsA vs CsA for the Treatment of Newly Diagnosed Non-Transfusion-Dependent NSAA
NCT06426043	PHASE4	NOT_YET_RECRUITING	A Prospective Study on the Treatment of Recurrent/Refractory/Intolerable NSAA With Lusutrombopag
NCT06516484	PHASE4	NOT_YET_RECRUITING	Ropustin for Refractory Aplastic Anaemia After Radiotherapy - a Single-centre, Prospective, Open-label, Single-arm Study
NCT06525948	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of rhTPO in Combination With Cyclosporine Versus Cyclosporine Alone in the Treatment of TD-NSAA
NCT06535685	PHASE4	NOT_YET_RECRUITING	A Study of Romiplostim for the Treatment of Refractory Transfusion-dependent NSAA
NCT01818726	PHASE4	TERMINATED	Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients
NCT01995331	PHASE4	UNKNOWN	Moderate-dose Cyclophosphamide for Childhood Acquired Aplastic Anemia
NCT01997372	PHASE4	UNKNOWN	Different Doses of Anti-thymocyte Globin to Treat Child Severe Aplastic Anemia
NCT02745717	PHASE4	COMPLETED	The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
NCT02838992	PHASE4	UNKNOWN	ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
NCT02875743	PHASE4	COMPLETED	King’s Invasive Aspergillosis Study II
NCT03176849	PHASE4	COMPLETED	A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT
NCT03896971	PHASE4	COMPLETED	Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia
NCT05996393	PHASE4	COMPLETED	CsA+ATG+AVA vs. CsA+AVA for the Treatment of Newly-diagnosed SAA in the Elderly
NCT06004791	PHASE4	UNKNOWN	A Prospective, Randomized, Controlled Study of rhTPO in Combination With Herombopag + CsA vs Herombopag + CsA for the Treatment of Primary TD-NSAA
NCT06009965	PHASE4	UNKNOWN	Efficacy of IST Combined With TPO-RA in the Treatment of AA and Establishment of a Recurrence Prediction System
NCT06069180	PHASE4	UNKNOWN	The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA
NCT05600426	PHASE3	ACTIVE_NOT_RECRUITING	A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
NCT07001397	PHASE3	NOT_YET_RECRUITING	Study on the Short-term Efficacy and Safety of Recombinant Human Thrombopoietin Combined With Immunosuppressant Sequential Eltrombopag Ethanolamine Dry Suspension in the Treatment of SAA/TD-NSAA
NCT00004474	PHASE3	COMPLETED	Phase III Randomized Study of Cyclophosphamide With or Without Antithymocyte Globulin Before Bone Marrow Transplantation in Patients With Aplastic Anemia
NCT00455312	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
NCT01145976	PHASE3	UNKNOWN	Comparison of Cy-Atg vs Flu-Atg for the Conditioning Therapy in Allo-HCT for Adult Aplastic Anemia
NCT01163942	PHASE3	TERMINATED	Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF)
NCT01343680	PHASE3	TERMINATED	Trial of Two Central Venous Catheter (CVC) Flushing Schemes in Pediatric Hematology and Oncology Patients
NCT02099747	PHASE3	COMPLETED	hATG+CsA vs hATG+CsA+Eltrombopag for SAA
NCT02773290	PHASE2/PHASE3	COMPLETED	Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia
NCT03295058	PHASE2/PHASE3	UNKNOWN	Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients
NCT03825744	PHASE3	COMPLETED	Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia
NCT03957694	PHASE2/PHASE3	COMPLETED	Study of AMG531(Romiplostim) in Patients With Aplastic Anemia
NCT04095936	PHASE2/PHASE3	COMPLETED	Study of AMG531 (Romiplostim) in Patients With Aplastic Anemia
NCT04350606	PHASE3	COMPLETED	A Study to Assess Efficacy and Safety of PF-06462700 in Japanese Participants With Aplastic Anemia
NCT04728789	PHASE2/PHASE3	UNKNOWN	Avatrombopag Usage in NSAA
NCT05018936	PHASE2/PHASE3	UNKNOWN	Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT01174108	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
NCT01623167	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia
NCT01624805	PHASE2	RECRUITING	Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With Aplastic Anemia or Low or Intermediate-Risk Myelodysplastic Syndrome
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02828592	PHASE2	RECRUITING	Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	34
ROMIPLOSTIM	4	10
ELTROMBOPAG	4	8
AVATROMBOPAG	4	6
CYCLOSPORINE	4	6
2-MERCAPTOETHANESULFONIC ACID	4	4
LUSPATERCEPT	4	2
POSACONAZOLE	4	2
ALEMTUZUMAB	4	1
BUSULFAN	4	1
CLOFARABINE	4	1
DACLIZUMAB	4	1
DANAZOL	4	1
DEFERASIROX	4	1
FLUDARABINE PHOSPHATE	4	1
LEVAMISOLE	4	1
LUSUTROMBOPAG	4	1
MELPHALAN	4	1
NANDROLONE DECANOATE	4	1
FLUDARABINE	3	2
HETROMBOPAG OLAMINE	3	2
RAFUTROMBOPAG	3	2
MOTIXAFORTIDE	3	1
ANTILYMPHOCYTE IMMUNOGLOBULIN (HORSE)	2	3
DEXAMISOLE	2	1
CHEMBL406352	0	2
CHEMBL290077	0	2