Combined pulmonary fibrosis-emphysema syndrome

Summary

Combined pulmonary fibrosis-emphysema syndrome (MONDO:0017591) is a disease with 4 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 4
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	combined pulmonary fibrosis-emphysema syndrome
Mondo ID	MONDO:0017591
Orphanet	300564
ICD-11	1361267223
UMLS	C3872815
MedGen	838971
GARD	0021238
Is cancer (heuristic)	no

Also known as: CPFE

Data availability: 4 ClinVar variants.

Disease family

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

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

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance; association, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162779	NM_014883.4(FAM13A):c.843+16335C>A	FAM13A	Uncertain significance; association	no assertion criteria provided
1162781	NM_019009.4(TOLLIP):c.184-1067G>C	TOLLIP	Uncertain significance; association	no assertion criteria provided
672128	NM_004415.4(DSP):c.726+219T>G	DSP	Benign	criteria provided, single submitter
375480	NM_198253.3(TERT):c.1574-3777G>T	TERT	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 21 · 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
FAM13A	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:158687	Lethal acantholytic erosive disorder
DSP	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome
DSP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSP	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSP	Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome
DSP	Orphanet:50942	Striate palmoplantar keratoderma
DSP	Orphanet:65282	Carvajal syndrome

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
TOLLIP	HGNC:16476	ENSG00000078902	Q9H0E2	Toll-interacting protein	clinvar
FAM13A	HGNC:19367	ENSG00000138640	O94988	Protein FAM13A	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	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.
TOLLIP	Toll-interacting protein	Component of the signaling pathway of IL-1 and Toll-like receptors.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · 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
Scaffold/PPI	1	4.3×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TOLLIP	Other/Unknown	no		C2_dom, CUE, UBA-like_sf
FAM13A	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, FAM13
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
anterior cingulate cortex	1
cingulate cortex	1
right frontal lobe	1
jejunal mucosa	1
oocyte	1
secondary oocyte	1
hair follicle	1
skin of hip	1
upper leg skin	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
TOLLIP	263	ubiquitous	marker	right frontal lobe, anterior cingulate cortex, cingulate cortex
FAM13A	293	ubiquitous	marker	secondary oocyte, oocyte, jejunal mucosa
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
DSP	2,897
TOLLIP	2,543
FAM13A	830

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TERT	O14746	23
DSP	P15924	4
TOLLIP	Q9H0E2	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM13A	O94988	61.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 4 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
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	407.9×	0.040	TERT
Apoptotic cleavage of cell adhesion proteins	1	259.6×	0.040	DSP
Extension of Telomeres	1	150.3×	0.040	TERT
Telomere Extension By Telomerase	1	114.2×	0.040	TERT
Telomere Maintenance	1	92.1×	0.040	TERT
Neutrophil degranulation	2	11.5×	0.040	TOLLIP, DSP
RND1 GTPase cycle	1	66.4×	0.042	DSP
RND3 GTPase cycle	1	64.9×	0.042	DSP
Chromosome Maintenance	1	52.9×	0.046	TERT
MITF-M-dependent gene expression	1	45.3×	0.048	TERT
Interleukin-1 signaling	1	31.0×	0.052	TOLLIP
Formation of the beta-catenin:TCF transactivating complex	1	30.1×	0.052	TERT
TCF dependent signaling in response to WNT	1	29.4×	0.052	TERT
MITF-M-regulated melanocyte development	1	28.6×	0.052	TERT
Signaling by WNT	1	28.0×	0.052	TERT
Formation of the cornified envelope	1	22.0×	0.062	DSP
RHOA GTPase cycle	1	18.7×	0.068	FAM13A
RAC1 GTPase cycle	1	15.3×	0.078	FAM13A
Keratinization	1	13.9×	0.081	DSP
Cell Cycle	1	9.0×	0.117	TERT
Developmental Biology	1	3.6×	0.261	TERT
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 4 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	4213.0×	0.004	TERT
DNA strand elongation	1	4213.0×	0.004	TERT
siRNA transcription	1	4213.0×	0.004	TERT
positive regulation of transdifferentiation	1	4213.0×	0.004	TERT
RNA-templated DNA biosynthetic process	1	2106.5×	0.005	TERT
positive regulation of hair cycle	1	2106.5×	0.005	TERT
leukocyte activation	1	842.6×	0.009	TOLLIP
positive regulation of protein localization to nucleolus	1	702.2×	0.009	TERT
ventricular compact myocardium morphogenesis	1	601.9×	0.009	DSP
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	601.9×	0.009	DSP
desmosome organization	1	526.6×	0.009	DSP
establishment of protein localization to telomere	1	526.6×	0.009	TERT
siRNA processing	1	468.1×	0.009	TERT
protein localization to cell-cell junction	1	468.1×	0.009	DSP
telomere maintenance via recombination	1	383.0×	0.009	TERT
protein localization to endosome	1	383.0×	0.009	TOLLIP
peptide cross-linking	1	351.1×	0.009	DSP
regulation of ventricular cardiac muscle cell action potential	1	351.1×	0.009	DSP
phosphorylation	1	324.1×	0.009	TOLLIP
positive regulation of protein sumoylation	1	324.1×	0.009	TOLLIP
epithelial cell-cell adhesion	1	300.9×	0.009	DSP
replicative senescence	1	247.8×	0.011	TERT
positive regulation of vascular associated smooth muscle cell migration	1	247.8×	0.011	TERT
intermediate filament cytoskeleton organization	1	234.1×	0.011	DSP
interleukin-1-mediated signaling pathway	1	200.6×	0.011	TOLLIP
DNA biosynthetic process	1	200.6×	0.011	TERT
telomere maintenance via telomerase	1	183.2×	0.012	TERT
response to cadmium ion	1	183.2×	0.012	TERT
negative regulation of cellular senescence	1	162.0×	0.013	TERT
positive regulation of stem cell proliferation	1	131.7×	0.015	TERT

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
TOLLIP	0	0
FAM13A	0	0
DSP	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

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
DSP	2	Binding:2

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: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

10 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

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	TOLLIP, FAM13A, DSP

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)
TOLLIP	0	—
FAM13A	0	—
DSP	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.