Idiopathic pulmonary fibrosis

Summary

Idiopathic pulmonary fibrosis (MONDO:0800504) is a disease with 5 cohort genes and 518 clinical trials. Top therapeutic interventions include pirfenidone, nintedanib, and sildenafil.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 2,730
• Phenotypes (HPO): 20
• Clinical trials: 518

Clinical features

Epidemiology

Prevalence records

17 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	5.55	Worldwide	Validated
Point prevalence	1-5 / 10 000	16.125	Worldwide	Validated
Annual incidence	1-5 / 10 000	15.35	Canada	Validated
Annual incidence	1-9 / 100 000	1.3	Finland	Validated
Annual incidence	1-9 / 100 000	2.8	France	Validated
Annual incidence	1-9 / 100 000	2.6	Italy	Validated
Annual incidence	1-5 / 10 000	13	Korea, Republic of	Validated
Annual incidence	1-9 / 100 000	1.2	United Kingdom	Validated
Annual incidence	1-9 / 100 000	2.6	United States	Validated
Point prevalence	1-5 / 10 000	29.8	Canada	Validated
Point prevalence	1-9 / 100 000	8.6	Finland	Validated
Point prevalence	1-9 / 100 000	8.2	France	Validated
Point prevalence	1-5 / 10 000	21.2	Italy	Validated
Point prevalence	1-9 / 100 000	5.9	Japan	Validated
Point prevalence	1-5 / 10 000	37	Korea, Republic of	Validated
Point prevalence	1-5 / 10 000	11.6	United Kingdom	Validated
Point prevalence	1-9 / 100 000	6.7	United States	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0006530	Abnormal pulmonary interstitial morphology	Very frequent (80-99%)
HP:0001063	Acrocyanosis	Frequent (30-79%)
HP:0002020	Gastroesophageal reflux	Frequent (30-79%)
HP:0002110	Bronchiectasis	Frequent (30-79%)
HP:0002206	Pulmonary fibrosis	Frequent (30-79%)
HP:0002875	Exertional dyspnea	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0012735	Cough	Frequent (30-79%)
HP:0025175	Honeycomb lung	Frequent (30-79%)
HP:0025179	Ground-glass opacification on pulmonary HRCT	Frequent (30-79%)
HP:0025390	Reticular pattern on pulmonary HRCT	Frequent (30-79%)
HP:0030830	Crackles	Frequent (30-79%)
HP:0031631	Subpleural honeycombing	Frequent (30-79%)
HP:0031950	Usual interstitial pneumonia	Frequent (30-79%)
HP:0032341	Reduced forced vital capacity	Frequent (30-79%)
HP:0045051	Decreased DLCO	Frequent (30-79%)
HP:0100759	Clubbing of fingers	Frequent (30-79%)
HP:0003546	Exercise intolerance	Occasional (5-29%)
HP:0010444	Pulmonary insufficiency	Occasional (5-29%)
HP:0033367	Orthodeoxia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic pulmonary fibrosis
Mondo ID	MONDO:0800504
MeSH	D054990
Orphanet	2032
DOID	DOID:0050156
ICD-10-CM	J84.112
ICD-11	1074069640
NCIT	C35716
UMLS	C1800706
MedGen	321462
GARD	0028067
Is cancer (heuristic)	no

Also known as: IPF

Data availability: 2,730 ClinVar variants · 215 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › respiratory tract infectious disorder › pneumonia › idiopathic interstitial pneumonia › idiopathic pulmonary fibrosis

Related subtypes (9): lymphoid interstitial pneumonia, desquamative interstitial pneumonia, cryptogenic organizing pneumonia, combined pulmonary fibrosis-emphysema syndrome, acute interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease syndrome, non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, follicular bronchiolits

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

600 retrieved; paginated sample, class counts are floors:

305 uncertain significance, 228 likely benign, 40 conflicting classifications of pathogenicity, 16 pathogenic, 6 likely pathogenic, 3 pathogenic/likely pathogenic, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070657	NM_198253.3(TERT):c.198dup (p.Ala67fs)	LOC110806263	Pathogenic	criteria provided, single submitter
12738	NM_198253.3(TERT):c.219+1G>A	LOC110806263	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381898	NM_198253.3(TERT):c.247C>T (p.Arg83Ter)	LOC110806263	Pathogenic	criteria provided, single submitter
1418828	NM_198253.3(TERT):c.10_11dup (p.Pro5fs)	LOC110806263	Pathogenic	criteria provided, single submitter
1069288	NM_198253.3(TERT):c.1314del (p.Glu439fs)	TERT	Pathogenic	criteria provided, single submitter
1073945	NM_198253.3(TERT):c.1424del (p.Pro475fs)	TERT	Pathogenic	criteria provided, single submitter
1074268	NC_000005.9:g.(?1287194)(1297488_?)del	TERT	Pathogenic	criteria provided, single submitter
1075528	NM_198253.3(TERT):c.3235del (p.Leu1079fs)	TERT	Pathogenic	criteria provided, single submitter
12736	NM_198253.3(TERT):c.2594G>A (p.Arg865His)	TERT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1357479	NM_198253.3(TERT):c.923dup (p.Ser309fs)	TERT	Pathogenic	criteria provided, single submitter
1379443	NM_198253.3(TERT):c.1122del (p.Thr375fs)	TERT	Pathogenic	criteria provided, single submitter
1379483	NM_198253.3(TERT):c.2315_2330del (p.Tyr772fs)	TERT	Pathogenic	criteria provided, single submitter
1397003	NM_198253.3(TERT):c.598G>T (p.Glu200Ter)	TERT	Pathogenic	criteria provided, multiple submitters, no conflicts
1421091	NM_198253.3(TERT):c.767G>A (p.Trp256Ter)	TERT	Pathogenic	criteria provided, single submitter
1434641	NM_198253.3(TERT):c.1871_1872dup (p.Pro625fs)	TERT	Pathogenic	criteria provided, single submitter
1435798	NM_198253.3(TERT):c.1612G>T (p.Glu538Ter)	TERT	Pathogenic	criteria provided, single submitter
1437767	NM_198253.3(TERT):c.996del (p.Tyr333fs)	TERT	Pathogenic	criteria provided, single submitter
1457059	NM_198253.3(TERT):c.2461del (p.Arg821fs)	TERT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459137	NM_198253.3(TERT):c.329del (p.Gly110fs)	TERT	Pathogenic	criteria provided, single submitter
1065578	NM_198253.3(TERT):c.3026C>T (p.Ala1009Val)	TERT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067497	NM_198253.3(TERT):c.2970+2T>G	TERT	Likely pathogenic	criteria provided, single submitter
1338417	NM_198253.3(TERT):c.3157+1G>T	TERT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1348881	NC_000005.9:g.(?1282524)(1282759_?)dup	TERT	Likely pathogenic	criteria provided, single submitter
1485756	NM_198253.3(TERT):c.3118G>A (p.Ala1040Thr)	TERT	Likely pathogenic	criteria provided, single submitter
1502782	NM_198253.3(TERT):c.2286+1G>A	TERT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1156551	NM_198253.3(TERT):c.171C>T (p.Cys57=)	LOC110806263	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1402275	NM_198253.3(TERT):c.227G>C (p.Cys76Ser)	LOC110806263	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004721	NM_198253.3(TERT):c.2764A>T (p.Met922Leu)	TERT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009835	NM_198253.3(TERT):c.965C>T (p.Pro322Leu)	TERT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013653	NM_198253.3(TERT):c.2912G>A (p.Arg971His)	TERT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
SLC6A19	Orphanet:2116	Hartnup disease
SLC6A19	Orphanet:42062	Iminoglycinuria

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
NKD2	HGNC:17046	ENSG00000145506	Q969F2	Protein naked cuticle homolog 2	clinvar
ZDHHC11	HGNC:19158	ENSG00000188818	Q9H8X9	Palmitoyltransferase ZDHHC11	clinvar
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	clinvar
SLC6A19	HGNC:27960	ENSG00000174358	Q695T7	Sodium-dependent neutral amino acid transporter B(0)AT1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
NKD2	Protein naked cuticle homolog 2	Cell autonomous antagonist of the canonical Wnt signaling pathway.
ZDHHC11	Palmitoyltransferase ZDHHC11	Endoplasmic reticulum-localized palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes.
CLPTM1L	Lipid scramblase CLPTM1L	Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to th…
SLC6A19	Sodium-dependent neutral amino acid transporter B(0)AT1	Transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 5 · 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	5	1.8×	0.054

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
NKD2	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, Nkd-like
ZDHHC11	Other/Unknown	no		Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like
CLPTM1L	Other/Unknown	no		CLPTM1
SLC6A19	Other/Unknown	no		Na/ntran_symport, Neutral_aa_SLC6, SNS_sf

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	2
kidney epithelium	2
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
lung	1
right lung	1
upper lobe of left lung	1
cardiac muscle of right atrium	1
right hemisphere of cerebellum	1
right uterine tube	1
right lobe of thyroid gland	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
NKD2	130	broad	yes	upper lobe of left lung, right lung, lung
ZDHHC11	251		marker	right uterine tube, cardiac muscle of right atrium, right hemisphere of cerebellum
CLPTM1L	255	ubiquitous	marker	ileal mucosa, kidney epithelium, right lobe of thyroid gland
SLC6A19	67	tissue_specific	marker	ileal mucosa, kidney epithelium, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
CLPTM1L	1,606
SLC6A19	975
NKD2	745
ZDHHC11	401

Intra-cohort edges

A	B	Sources
CLPTM1L	TERT	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TERT	O14746	23
SLC6A19	Q695T7	21

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLPTM1L	Q96KA5	78.54
ZDHHC11	Q9H8X9	74.62
NKD2	Q969F2	56.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 5 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective transport of neurotransmitters by SLC6A19 causes Hartnup disorder (HND)	1	2855.0×	0.005	SLC6A19
Defective transport of amino acids by SLC6A19 causes Hartnup disorder (HND)	1	2855.0×	0.005	SLC6A19
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	407.9×	0.021	TERT
Extension of Telomeres	1	150.3×	0.040	TERT
Telomere Extension By Telomerase	1	114.2×	0.040	TERT
SLC-mediated transport of neurotransmitters	1	102.0×	0.040	SLC6A19
Telomere Maintenance	1	92.1×	0.040	TERT
Amino acid transport across the plasma membrane	1	75.1×	0.043	SLC6A19
Maturation of spike protein	1	66.4×	0.043	ZDHHC11
Chromosome Maintenance	1	52.9×	0.044	TERT
SLC transporter disorders	1	51.0×	0.044	SLC6A19
R-HSA-425366	1	45.3×	0.044	SLC6A19
MITF-M-dependent gene expression	1	45.3×	0.044	TERT
CHD6, CHD7, CHD8, CHD9 subfamily	1	37.1×	0.046	NKD2
Disorders of transmembrane transporters	1	34.8×	0.046	SLC6A19
R-HSA-425393	1	32.4×	0.046	SLC6A19
Formation of the beta-catenin:TCF transactivating complex	1	30.1×	0.046	TERT
TCF dependent signaling in response to WNT	1	29.4×	0.046	TERT
MITF-M-regulated melanocyte development	1	28.6×	0.046	TERT
Signaling by WNT	1	28.0×	0.046	TERT
SLC-mediated transmembrane transport	1	14.8×	0.082	SLC6A19
Cell Cycle	1	9.0×	0.126	TERT
Transport of small molecules	1	6.3×	0.169	SLC6A19
Developmental Biology	1	3.6×	0.270	TERT
Disease	1	3.3×	0.283	SLC6A19
Signal Transduction	1	2.5×	0.339	TERT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA-templated transcription	1	3370.4×	0.004	TERT
DNA strand elongation	1	3370.4×	0.004	TERT
siRNA transcription	1	3370.4×	0.004	TERT
positive regulation of transdifferentiation	1	3370.4×	0.004	TERT
RNA-templated DNA biosynthetic process	1	1685.2×	0.004	TERT
positive regulation of hair cycle	1	1685.2×	0.004	TERT
Golgi vesicle fusion to target membrane	1	1685.2×	0.004	NKD2
viral life cycle	1	842.6×	0.008	SLC6A19
positive regulation of protein localization to nucleolus	1	561.7×	0.010	TERT
establishment of protein localization to telomere	1	421.3×	0.012	TERT
siRNA processing	1	374.5×	0.012	TERT
telomere maintenance via recombination	1	306.4×	0.014	TERT
positive regulation of protein processing	1	240.7×	0.015	NKD2
peptidyl-L-cysteine S-palmitoylation	1	240.7×	0.015	ZDHHC11
replicative senescence	1	198.3×	0.016	TERT
positive regulation of vascular associated smooth muscle cell migration	1	198.3×	0.016	TERT
neutral amino acid transport	1	177.4×	0.017	SLC6A19
DNA biosynthetic process	1	160.5×	0.017	TERT
telomere maintenance via telomerase	1	146.5×	0.017	TERT
response to cadmium ion	1	146.5×	0.017	TERT
negative regulation of cellular senescence	1	129.6×	0.019	TERT
positive regulation of defense response to virus by host	1	105.3×	0.021	ZDHHC11
positive regulation of stem cell proliferation	1	105.3×	0.021	TERT
negative regulation of endothelial cell apoptotic process	1	99.1×	0.021	TERT
positive regulation of D-glucose import across plasma membrane	1	91.1×	0.022	TERT
positive regulation of vascular associated smooth muscle cell proliferation	1	86.4×	0.023	TERT
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	82.2×	0.023	TERT
positive regulation of G1/S transition of mitotic cell cycle	1	80.2×	0.023	TERT
positive regulation of Wnt signaling pathway	1	76.6×	0.023	TERT
negative regulation of Wnt signaling pathway	1	68.8×	0.025	NKD2

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Pirfenidone	Approved (phase 4)

40 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Acetylcysteine	Phase 3
Admilparant	Phase 3
Ambrisentan	Phase 3
Bosentan	Phase 3
INTERFERON GAMMA-1B	Phase 3
Lansoprazole	Phase 3
Methylprednisolone	Phase 3
Minocycline	Phase 3
Nintedanib	Phase 3
Pamrevlumab	Phase 3
Prednisolone	Phase 3
Prednisone	Phase 3
Sildenafil	Phase 3
Sulfamethoxazole	Phase 3
Thalidomide	Phase 3
Thrombomodulin Alfa	Phase 3
Treprostinil	Phase 3
Trimethoprim	Phase 3
Warfarin	Phase 3
Zinpentraxin Alfa	Phase 3
Ziritaxestat	Phase 3
Axatilimab	Phase 2
Azathioprine	Phase 2
Beclomethasone Dipropionate	Phase 2
Belumosudil	Phase 2
Carbon Monoxide	Phase 2
Gefapixant	Phase 2
Ianalumab	Phase 2
Lebrikizumab	Phase 2
Losartan	Phase 2
Macitentan	Phase 2
Nalbuphine	Phase 2
Omeprazole	Phase 2
Oxygen	Phase 2
Rituximab	Phase 2
Tazarotene	Phase 2
Tralokinumab	Phase 2
Vismodegib	Phase 2
Voxelotor	Phase 2
Zileuton	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 3

Druggability breadth: 3 of 5 evidence-associated genes (60%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TERT	BERBERINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TERT	10	4
SLC6A19	1	2
NKD2	0	0
ZDHHC11	0	0
CLPTM1L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT
ALLICIN	2	TERT
OLEIC ACID	2	TERT
ETHACRIDINE	2	TERT
CINROMIDE	2	SLC6A19

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TERT	391	Binding:389, Functional:2
SLC6A19	4	Functional:3, Binding:1
CLPTM1L	1	Binding:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TERT	391

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

11 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.

Compound	Max phase	Cohort target (bioactivity)
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT
ALLICIN	2	TERT
OLEIC ACID	2	TERT
ETHACRIDINE	2	TERT
CINROMIDE	2	SLC6A19

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TERT
B	Phased (≥1) drug, not yet approved	1	SLC6A19
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	NKD2, ZDHHC11, CLPTM1L

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLPTM1L	1	TERT
NKD2	0	—
ZDHHC11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 518.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	225
PHASE2	120
PHASE1	88
PHASE3	46
PHASE1/PHASE2	14
PHASE4	12
EARLY_PHASE1	9
PHASE2/PHASE3	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT01321996	PHASE4	TERMINATED	68Ga-DOTA-NOC PET/CT in Patients With Idiopathic Pulmonary Fibrosis
NCT01382368	PHASE4	UNKNOWN	Acute Effect of Sildenafil on Exercise Tolerance and Functional Capacity in COPD, IPF and Post Pneumonectomy Patients
NCT02579603	PHASE4	COMPLETED	Safety, Tolerability and PK of Nintedanib in Combination With Pirfenidone in IPF
NCT02598193	PHASE4	COMPLETED	Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)
NCT02606877	PHASE4	COMPLETED	A Study to Compare the Amount of Nintedanib and Pirfenidone in the Blood When Nintedanib and Pirfenidone Are Given Separately or in Combination
NCT02788474	PHASE4	COMPLETED	Effect of Nintedanib on Biomarkers of Extracellular Matrix Turnover in Patients With Idiopathic Pulmonary Fibrosis and Limited Forced Vital Capacity Impairment
NCT03503188	PHASE4	COMPLETED	Digital Auscultation Test - IPF Data Collection
NCT03717012	PHASE4	TERMINATED	Study of Pulmonary Rehabilitation in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT03939520	PHASE4	COMPLETED	Management of Progressive Disease in Idiopathic Pulmonary Fibrosis
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT04965298	PHASE3	RECRUITING	Treating People With Idiopathic Pulmonary Fibrosis With the Addition of Lansoprazole
NCT06003426	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Idiopathic Pulmonary Fibrosis
NCT06125327	PHASE2/PHASE3	RECRUITING	SC1011 Twice Daily vs Placebo in Patients Diagnosed With Idiopathic Pulmonary Fibrosis (IPF)
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
NCT07082842	PHASE3	RECRUITING	Confirmatory Clinical Study of HEC585 Tablets in Patients With IPF
NCT07284602	PHASE3	NOT_YET_RECRUITING	Trial to Evaluate the Efficacy and Safety of LYT-100 (Deupirfenidone) Compared to Pirfenidone in Adults With Idiopathic Pulmonary Fibrosis (IPF)
NCT07299695	PHASE3	RECRUITING	Intravenous Immunoglobulin for the Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis
NCT07464912	PHASE3	RECRUITING	A Adaptive Design Clinical Trial to Evaluate the Efficacy and Safety of TDI01 Suspension in the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
NCT07519070	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of HSK44459 Tablets in Patients With Idiopathic Pulmonary Fibrosis
NCT07520110	PHASE3	NOT_YET_RECRUITING	Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis
NCT00047645	PHASE3	COMPLETED	A Study of the Safety and Efficacy Interferon-Gamma 1b in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT00071461	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan in Patients With Idiopathic Pulmonary Fibrosis
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
NCT00105183	PHASE3	COMPLETED	EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection
NCT00131274	PHASE2/PHASE3	COMPLETED	Gleevec Idiopathic Pulmonary Fibrosis (IPF) Study
NCT00203697	PHASE3	UNKNOWN	Minocycline Therapy for Lung Scarring in Patients With Idiopathic Pulmonary Fibrosis - a Pilot Study
NCT00287716	PHASE3	COMPLETED	Three-Arm Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis
NCT00287729	PHASE3	COMPLETED	Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis
NCT00391443	PHASE3	COMPLETED	BUILD 3: Bosentan Use in Interstitial Lung Disease
NCT00600028	PHASE3	COMPLETED	Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis With Thalidomide
NCT00631475	PHASE3	COMPLETED	Open Label Extension Study in Patients With Idiopathic Pulmonary Fibrosis Who Completed Protocol AC-052-321/ BUILD 3 / NCT00391443
NCT00662038	PHASE3	COMPLETED	Open-Label Study of the Long Term Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT00768300	PHASE3	TERMINATED	(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
NCT00879229	PHASE3	TERMINATED	ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
NCT00957242	PHASE3	TERMINATED	AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis
NCT00981747	PHASE2/PHASE3	TERMINATED	Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PIRFENIDONE	4	31
NINTEDANIB	4	13
SILDENAFIL	4	9
BOSENTAN	4	5
TREPROSTINIL	4	5
AMBRISENTAN	4	2
GEFAPIXANT	4	2
MACITENTAN	4	2
VISMODEGIB	4	2
VOXELOTOR	4	2
AXATILIMAB	4	1
AZATHIOPRINE	4	1
BECLOMETHASONE DIPROPIONATE	4	1
BELUMOSUDIL	4	1
CROMOLYN SODIUM	4	1
DEXTROMETHORPHAN	4	1
DEXTROMETHORPHAN HYDROBROMIDE	4	1
ESOMEPRAZOLE	4	1
IDELALISIB	4	1
INTERFERON GAMMA-1B	4	1
LANSOPRAZOLE	4	1
LEBRIKIZUMAB	4	1
MINOCYCLINE	4	1
MORPHINE SULFATE	4	1
NANDROLONE DECANOATE	4	1
NEBIVOLOL	4	1
NITRIC OXIDE	4	1
OCTREOTIDE	4	1
SPINOSAD	4	1
TAZAROTENE	4	1