Pneumoconiosis

Summary

Pneumoconiosis (MONDO:0015926) is a disease (an umbrella term covering 14 Mondo subtypes) with 6 cohort genes (3 GWAS associations across 8 studies) and 12 clinical trials. Top therapeutic interventions include pirfenidone.

At a glance

• Umbrella term: 14 Mondo subtypes
• Cohort genes: 6
• GWAS associations: 3
• Clinical trials: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pneumoconiosis
Mondo ID	MONDO:0015926
MeSH	D011009
Orphanet	182098
DOID	DOID:10316
ICD-11	611962875
NCIT	C26861
SNOMED CT	40122008
UMLS	C0032273
MedGen	19360
GARD	0020245
MedDRA	10035653
Is cancer (heuristic)	no

Also known as: Black lung disease · coal worker’s pneumoconiosis

Data availability: 3 GWAS associations (8 studies).

Disease family

An umbrella term covering 14 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › lung disorder › interstitial lung disease › pneumoconiosis

Related subtypes (13): pulmonary fibrosis, bronchiolitis obliterans syndrome, pulmonary fibrosis-hepatic hyperplasia-bone marrow hypoplasia syndrome, interstitial lung disease specific to childhood, isolated pulmonary capillaritis, interstitial lung disease specific to adulthood, drug or radiation exposure-related interstitial lung disease, hypersensitivity pneumonitis, secondary pulmonary hemosiderosis, inherited interstitial lung disease, radiation pneumonitis, bronchiolocentric pattern of interstitial pneumonia, idiopathic pulmonary fibrosis

Subtypes (14): mixed mineral dust pneumoconiosis, baritosis, pneumoconiosis due to talc, slate pneumoconiosis, Caplan syndrome, silicosis, anthracosilicosis, anthracosis, byssinosis, pulmonary hemosiderosis, chronic beryllium disease, asbestosis, mixed dust pneumoconiosis, graphite pneumoconiosis

Genetics & variants

GWAS landscape

3 GWAS associations across 8 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs73329476	2e-08	CPM - CPSF6	T	2.17
rs4320486	4e-06	LAMB1	C	1.69
rs117626015	5e-06	PDZRN4	C	2.43

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478151	Verma A	2024	2,077	447,808	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473717	UK Biobank Whole-Genome Sequencing Consortium	2025	791	457,649	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90018900	Sakaue S	2021	433	478,607	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90436228	Zhou W	2018	234	397,411	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90481090	Verma A	2024	213	121,457	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482085	Verma A	2024	213	121,457	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST002515	Chu M	2014	202	0	A genome-wide association study identifies susceptibility loci of silica-related pneumoconiosis in Han Chinese.
GCST90018680	Sakaue S	2021	85	176,974	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	1
regulatory_region_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs73329476	12	69110303	C>T	0.102	intergenic_variant	CPM - CPSF6	2e-08	Tier 4: intronic/intergenic
rs4320486	7	108003532	C>G,T	0.245	regulatory_region_variant	LAMB1	4e-06	Tier 3: regulatory
rs117626015	12	41230993	T>C	0.04	intron_variant	PDZRN4	5e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNTN1	Orphanet:210163	Congenital lethal myopathy, Compton-North type
LAMB1	Orphanet:352682	Cobblestone lissencephaly without muscular or ocular involvement
MDM2	Orphanet:524	Li-Fraumeni syndrome
MDM2	Orphanet:99970	Dedifferentiated liposarcoma
MDM2	Orphanet:99971	Well-differentiated liposarcoma

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CPSF6	HGNC:13871	ENSG00000111605	Q16630	Cleavage and polyadenylation specificity factor subunit 6	gwas
CNTN1	HGNC:2171	ENSG00000018236	Q12860	Contactin-1	gwas
CPM	HGNC:2311	ENSG00000135678	P14384	Carboxypeptidase M	gwas
PDZRN4	HGNC:30552	ENSG00000165966	Q6ZMN7	PDZ domain-containing RING finger protein 4	gwas
LAMB1	HGNC:6486	ENSG00000091136	P07942	Laminin subunit beta-1	gwas
MDM2	HGNC:6973	ENSG00000135679	Q00987	E3 ubiquitin-protein ligase Mdm2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPSF6	Cleavage and polyadenylation specificity factor subunit 6	Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3’-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs.
CNTN1	Contactin-1	Contactins mediate cell surface interactions during nervous system development.
CPM	Carboxypeptidase M	Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins.
LAMB1	Laminin subunit beta-1	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
MDM2	E3 ubiquitin-protein ligase Mdm2	E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.33

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
Protease	1	6.1×	0.252
Antibody/Immunoglobulin	1	4.9×	0.252
Transcription factor	2	2.8×	0.252
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPSF6	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, CPSF6_RRM
CNTN1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
CPM	Protease	yes	3.4.17.12	Peptidase_M14, CarboxyPept-like_regulatory, CPM_N
PDZRN4	Transcription factor	no		PDZ, Znf_RING, Znf_RING/FYVE/PHD
LAMB1	Other/Unknown	no		EGF, LE_dom, Laminin_N
MDM2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RanBP2, SWIB_MDM2_domain

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
bone marrow cell	1
ganglionic eminence	1
Brodmann (1909) area 23	1
cortical plate	1
endothelial cell	1
adipose tissue	1
lower lobe of lung	1
subcutaneous adipose tissue	1
blood vessel layer	1
cauda epididymis	1
popliteal artery	1
nerve	1
omental fat pad	1
tibial nerve	1
adrenal tissue	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPSF6	291	ubiquitous	marker	ganglionic eminence, bone marrow cell, calcaneal tendon
CNTN1	228	broad	marker	cortical plate, Brodmann (1909) area 23, endothelial cell
CPM	258	ubiquitous	marker	lower lobe of lung, subcutaneous adipose tissue, adipose tissue
PDZRN4	211	tissue_specific	marker	cauda epididymis, blood vessel layer, popliteal artery
LAMB1	284	ubiquitous	marker	nerve, tibial nerve, omental fat pad
MDM2	274	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MDM2	9,892
CPSF6	3,019
CNTN1	2,717
LAMB1	1,970
PDZRN4	1,712
CPM	595

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MDM2	Q00987	147
CPSF6	Q16630	16
LAMB1	P07942	3
CNTN1	Q12860	2
CPM	P14384	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PDZRN4	Q6ZMN7	60.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 78. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neurofascin interactions	1	285.5×	0.039	CNTN1
AKT phosphorylates targets in the cytosol	1	163.1×	0.039	MDM2
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	152.3×	0.039	MDM2
Stabilization of p53	1	152.3×	0.039	MDM2
p53-Dependent G1 DNA Damage Response	1	142.8×	0.039	MDM2
p53-Dependent G1/S DNA damage checkpoint	1	142.8×	0.039	MDM2
G1/S DNA Damage Checkpoints	1	134.3×	0.039	MDM2
Signaling by cytosolic FGFR1 fusion mutants	1	126.9×	0.039	CPSF6
MET promotes cell motility	1	120.2×	0.039	LAMB1
SUMOylation of transcription factors	1	114.2×	0.039	MDM2
Processing of Intronless Pre-mRNAs	1	114.2×	0.039	CPSF6
Transcriptional Regulation by NPAS4	1	114.2×	0.039	MDM2
Trafficking of AMPA receptors	1	108.8×	0.039	MDM2
Regulation of TP53 Activity through Methylation	1	108.8×	0.039	MDM2
Regulation of TP53 Expression and Degradation	1	103.8×	0.039	MDM2
Attachment of bacteria to epithelial cells	1	99.3×	0.039	LAMB1
NPAS4 regulates expression of target genes	1	99.3×	0.039	MDM2
L1CAM interactions	2	48.1×	0.039	CNTN1, LAMB1
Post-translational protein modification	3	11.5×	0.039	CPM, LAMB1, MDM2
Metabolism of proteins	3	7.4×	0.039	CPM, LAMB1, MDM2
NOTCH2 Activation and Transmission of Signal to the Nucleus	1	87.8×	0.040	CNTN1
Constitutive Signaling by AKT1 E17K in Cancer	1	84.6×	0.040	MDM2
Laminin interactions	1	76.1×	0.040	LAMB1
MET activates PTK2 signaling	1	76.1×	0.040	LAMB1
PI3K/AKT Signaling in Cancer	1	73.7×	0.040	MDM2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	73.7×	0.040	LAMB1
Activated NOTCH1 Transmits Signal to the Nucleus	1	71.4×	0.040	CNTN1
Oncogene Induced Senescence	1	67.2×	0.040	MDM2
Signaling by MET	1	63.4×	0.040	LAMB1
Formation of the dystrophin-glycoprotein complex (DGC)	1	61.7×	0.040	LAMB1

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
positive regulation of muscle cell differentiation	2	449.4×	7e-04	LAMB1, MDM2
neuronal-glial interaction involved in cerebral cortex radial glia guided migration	1	3370.4×	0.007	LAMB1
cellular response to vitamin B1	1	3370.4×	0.007	MDM2
response to formaldehyde	1	3370.4×	0.007	MDM2
response to ether	1	1123.5×	0.012	MDM2
response to water-immersion restraint stress	1	1123.5×	0.012	MDM2
traversing start control point of mitotic cell cycle	1	842.6×	0.012	MDM2
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	842.6×	0.012	MDM2
mRNA alternative polyadenylation	1	842.6×	0.012	CPSF6
positive regulation of RNA export from nucleus	1	674.1×	0.012	CPSF6
cellular response to alkaloid	1	674.1×	0.012	MDM2
cellular response to UV-C	1	674.1×	0.012	MDM2
regulation of basement membrane organization	1	561.7×	0.012	LAMB1
central nervous system myelin formation	1	481.5×	0.012	CNTN1
cellular response to antibiotic	1	481.5×	0.012	MDM2
fibroblast activation	1	481.5×	0.012	MDM2
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	481.5×	0.012	MDM2
atrial septum development	1	421.3×	0.013	MDM2
co-transcriptional mRNA 3’-end processing, cleavage and polyadenylation pathway	1	374.5×	0.014	CPSF6
response to magnesium ion	1	280.9×	0.017	MDM2
positive regulation of integrin-mediated signaling pathway	1	259.3×	0.017	LAMB1
atrioventricular valve morphogenesis	1	240.7×	0.017	MDM2
peptide metabolic process	1	240.7×	0.017	CPM
cardiac septum morphogenesis	1	240.7×	0.017	MDM2
negative regulation of signal transduction by p53 class mediator	1	240.7×	0.017	MDM2
negative regulation of protein processing	1	224.7×	0.017	MDM2
negative regulation of DNA damage response, signal transduction by p53 class mediator	1	224.7×	0.017	MDM2
protein heterotetramerization	1	210.7×	0.017	CPSF6
positive regulation of vascular associated smooth muscle cell migration	1	198.3×	0.017	MDM2
response to iron ion	1	187.2×	0.017	MDM2

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

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

Drug	Highest phase
Pirfenidone	Phase 3

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
MDM2	NITROFURANTOIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MDM2	14	4
CPSF6	0	0
CNTN1	0	0
CPM	0	0
PDZRN4	0	0
LAMB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	MDM2
APOMORPHINE	4	MDM2
CYTARABINE	4	MDM2
IDASANUTLIN	3	MDM2
NAVTEMADLIN	3	MDM2
MILADEMETAN	3	MDM2
BRIGIMADLIN	3	MDM2
THIRAM	2	MDM2
SIREMADLIN	2	MDM2
ALRIZOMADLIN	2	MDM2
SAR-405838	1	MDM2
PF-03758309	1	MDM2
CGM-097	1	MDM2
RO-5045337	1	MDM2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
MDM2	1,007	Binding:979, Functional:28
CPSF6	1	Binding:1
CNTN1	1	Binding:1
CPM	1	Binding:1
LAMB1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CPM	3.4.17.12	carboxypeptidase M
MDM2	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MDM2	1,007

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

14 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)
NITROFURANTOIN	4	MDM2
APOMORPHINE	4	MDM2
CYTARABINE	4	MDM2
IDASANUTLIN	3	MDM2
NAVTEMADLIN	3	MDM2
MILADEMETAN	3	MDM2
BRIGIMADLIN	3	MDM2
THIRAM	2	MDM2
SIREMADLIN	2	MDM2
ALRIZOMADLIN	2	MDM2
SAR-405838	1	MDM2
PF-03758309	1	MDM2
CGM-097	1	MDM2
RO-5045337	1	MDM2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MDM2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	CNTN1, CPM
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	CPSF6, PDZRN4, LAMB1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CPSF6	1	—
CNTN1	1	—
CPM	1	—
PDZRN4	0	—
LAMB1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE1	2
PHASE3	1
PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05288179	PHASE3	RECRUITING	Efficacy and Safety of Pirfenidone Capsules in the Treatment of Pneumoconiosis
NCT07178184	PHASE2	NOT_YET_RECRUITING	Evaluating the Efficacy and Safety of Modified Qing-Zao-Jiu-Fei Decoction on Pneumoconiosis Patients
NCT02668068	PHASE1	COMPLETED	A Study on Pneumoconiosis Treated With Whole-lung Lavage Combined With Mesenchymal Stem Cells
NCT02790762	PHASE1	UNKNOWN	Human Umbilical Cord-Mesenchymal Stem Cells for Pneumoconiosis
NCT05365802	EARLY_PHASE1	RECRUITING	FAPI PET for Lung Fibrosis
NCT06563674	Not specified	RECRUITING	Acceptance-based Healthy Lifestyles Program for Patients With Pneumoconiosis
NCT07077382	Not specified	RECRUITING	Pneumoconiosis and Dust Exposure China Cohort
NCT00005280	Not specified	COMPLETED	Specialized Center of Research in Occupational and Immunologic Lung Disease
NCT04022902	Not specified	COMPLETED	The Experience of Patients and Family Caregivers in Managing Pneumoconiosis in the Family Context
NCT04841200	Not specified	UNKNOWN	TCM for Coal Worker’s Pneumoconiosis
NCT04952675	Not specified	UNKNOWN	Evaluation of Pneumoconiosis High Risk Early Warning Models
NCT04963348	Not specified	COMPLETED	Potential of Deep Learning in Assessing Pneumoconiosis Depicted on Digital Chest Radiography

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PIRFENIDONE	4	1