Interstitial lung disease 2
diseaseOn this page
Also known as fibrocystic pulmonary dysplasiafibrosing alveolitis, cryptogenicidiopathic pulmonary fibrosis, familialinterstitial pneumonitis, usualpulmonary fibrosis, idiopathic
Summary
Interstitial lung disease 2 (MONDO:0800497) is a disease caused by SFTPA2 (GenCC Strong), with 26 cohort genes and 2 clinical trials. The dominant Reactome pathway is Defective CSF2RB causes SMDP5 (4 cohort genes).
At a glance
- Causal gene: SFTPA2 (GenCC Strong)
- Cohort genes: 26
- ClinVar variants: 194
- Clinical trials: 2
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | interstitial lung disease 2 |
| Mondo ID | MONDO:0800497 |
| OMIM | 178500 |
| DOID | DOID:0060971 |
| UMLS | C5561926 |
| MedGen | 1794136 |
| GARD | 0028066 |
| Is cancer (heuristic) | no |
Also known as: fibrocystic pulmonary dysplasia · fibrosing alveolitis, cryptogenic · idiopathic pulmonary fibrosis, familial · interstitial pneumonitis, usual · pulmonary fibrosis, idiopathic
Data availability: 194 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited interstitial lung disease › interstitial lung disease 2
Related subtypes (12): pulmonary fibrosis and/or bone marrow failure, telomere-related, hypersensitivity pneumonitis, familial, alveolar capillary dysplasia with misalignment of pulmonary veins, Niemann-Pick disease type B, interstitial lung disease due to ABCA3 deficiency, lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome, Hermansky-Pudlak syndrome with pulmonary fibrosis, familial hypocalciuric hypercalcemia, SFTPC-related interstitial lung disease, interstitial lung disease 1, Rajab interstitial lung disease with brain calcifications, Lane Hamilton syndrome
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
194 retrieved; paginated sample, class counts are floors:
82 uncertain significance, 39 conflicting classifications of pathogenicity, 16 pathogenic, 15 benign, 11 benign/likely benign, 10 pathogenic/likely pathogenic, 9 likely benign, 6 likely pathogenic, 2 uncertain significance; association, 1 pathogenic/likely risk allele, 1 benign; risk factor, 1 not provided, 1 likely risk allele
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 203381 | NM_001089.3(ABCA3):c.875A>T (p.Glu292Val) | ABCA3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 831918 | NC_000005.10:g.(?218349)(1297373_?)del | AHRR | Pathogenic | criteria provided, single submitter |
| 12738 | NM_198253.3(TERT):c.219+1G>A | LOC110806263 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 36945 | NM_198253.3(TERT):c.164T>A (p.Leu55Gln) | LOC110806263 | Pathogenic | no assertion criteria provided |
| 7327 | NR_001566.3(TERC):n.98G>A | LOC110806306 | Pathogenic | no assertion criteria provided |
| 831255 | NC_000005.10:g.(?218346)(1295046_?)del | NKD2 | Pathogenic | criteria provided, single submitter |
| 217284 | NM_001283009.2(RTEL1):c.2413+1G>C | RTEL1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 217517 | NM_001283009.2(RTEL1):c.958+2dup | RTEL1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 42018 | NM_001283009.1(RTEL1):c.3791G>A (p.Arg1264His) | RTEL1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 42020 | NM_001283009.2(RTEL1):c.2920C>T (p.Arg974Ter) | RTEL1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 217283 | NM_001283009.2(RTEL1):c.2219_2227del (p.His740_Ile742del) | RTEL1-TNFRSF6B | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 217518 | NM_001283009.2(RTEL1):c.1482-1G>A | RTEL1-TNFRSF6B | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 217519 | NM_001283009.2(RTEL1):c.1546G>C (p.Val516Leu) | RTEL1-TNFRSF6B | Pathogenic | criteria provided, single submitter |
| 559538 | NM_001283009.2(RTEL1):c.3559C>T (p.Gln1187Ter) | RTEL1-TNFRSF6B | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13199 | NM_001098668.4(SFTPA2):c.692G>T (p.Gly231Val) | SFTPA2 | Pathogenic/Likely risk allele | no assertion criteria provided |
| 13200 | NM_001098668.4(SFTPA2):c.593T>C (p.Phe198Ser) | SFTPA2 | Pathogenic | no assertion criteria provided |
| 1322020 | NM_001098668.4(SFTPA2):c.512A>T (p.Asn171Ile) | SFTPA2 | Pathogenic | no assertion criteria provided |
| 1325405 | NM_001098668.4(SFTPA2):c.697T>A (p.Trp233Arg) | SFTPA2 | Pathogenic | no assertion criteria provided |
| 1074267 | NC_000005.9:g.(?1253843)(1297488_?)del | 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 |
| 12737 | NM_198253.3(TERT):c.2240del (p.Val747fs) | TERT | Pathogenic | criteria provided, single submitter |
| 29899 | NM_198253.3(TERT):c.1892G>A (p.Arg631Gln) | TERT | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 36944 | NM_198253.3(TERT):c.2583-2A>C | TERT | Pathogenic | no assertion criteria provided |
| 39123 | NM_198253.3(TERT):c.*6_*182del | TERT | Pathogenic | no assertion criteria provided |
| 410651 | NM_198253.3(TERT):c.336dup (p.Glu113fs) | TERT | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 584005 | NC_000005.10:g.(?1280152)(1280344_?)del | TERT | Pathogenic | criteria provided, single submitter |
| 843002 | NM_198253.3(TERT):c.1434G>A (p.Trp478Ter) | TERT | Pathogenic | criteria provided, single submitter |
| 915844 | NM_001089.3(ABCA3):c.2883C>T (p.Gly961=) | ABCA3 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 915845 | NM_001089.3(ABCA3):c.4885dup (p.Ala1629fs) | ABCA3 | Likely pathogenic | criteria provided, single submitter |
| 559539 | NM_173842.3(IL1RN):c.63A>G (p.Ser21=) | IL1RN | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| SFTPA2 | Strong | Autosomal dominant | interstitial lung disease 2 | 5 |
| MUC5B | Limited | Autosomal recessive | interstitial lung disease | 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SFTPA2 | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| MUC5B | Orphanet:171700 | Diffuse panbronchiolitis |
| MUC5B | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| MUC5B | Orphanet:686465 | Fibrotic hypersensitivity pneumonitis |
| SFTPA1 | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| SFTPC | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| SFTPC | Orphanet:217566 | Chronic respiratory distress with surfactant metabolism deficiency |
| SFTPC | Orphanet:440392 | Interstitial lung disease due to SP-C deficiency |
| SFTPC | Orphanet:685082 | Pediatric acute respiratory distress syndrome |
| 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 |
| NKX2-1 | Orphanet:1429 | Benign hereditary chorea |
| NKX2-1 | Orphanet:146 | Differentiated thyroid carcinoma |
| NKX2-1 | Orphanet:209905 | Brain-lung-thyroid syndrome |
| NKX2-1 | Orphanet:95713 | Athyreosis |
| HPS4 | Orphanet:231500 | Hermansky-Pudlak syndrome due to BLOC-3 deficiency |
| RTEL1 | Orphanet:1775 | Dyskeratosis congenita |
| RTEL1 | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| RTEL1 | Orphanet:3322 | Hoyeraal-Hreidarsson syndrome |
| DTNBP1 | Orphanet:231531 | Hermansky-Pudlak syndrome due to BLOC-1 deficiency |
| FAM13A | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| CTC1 | Orphanet:1775 | Dyskeratosis congenita |
| CTC1 | Orphanet:313838 | Coats plus syndrome |
| 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 |
| ABCA3 | Orphanet:2032 | Idiopathic pulmonary fibrosis |
| ABCA3 | Orphanet:217563 | Neonatal acute respiratory distress syndrome |
| ABCA3 | Orphanet:440402 | Interstitial lung disease due to ABCA3 deficiency |
| ABCA3 | Orphanet:685082 | Pediatric acute respiratory distress syndrome |
| IL1RN | Orphanet:210115 | Sterile multifocal osteomyelitis with periostitis and pustulosis |
| LAMA3 | Orphanet:2407 | Laryngo-onycho-cutaneous syndrome |
| LAMA3 | Orphanet:79402 | Intermediate generalized junctional epidermolysis bullosa |
| LAMA3 | Orphanet:79404 | Severe generalized junctional epidermolysis bullosa |
| LAMA4 | Orphanet:154 | Familial isolated dilated cardiomyopathy |
Cohort genes → proteins
26 cohort genes, 24 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 26 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SFTPA2 | HGNC:10799 | ENSG00000185303 | Q8IWL1 | Pulmonary surfactant-associated protein A2 | gencc,clinvar |
| MUC5B | HGNC:7516 | ENSG00000117983 | Q9HC84 | Mucin-5B | gencc,clinvar |
| SFTPA1 | HGNC:10798 | ENSG00000122852 | Q8IWL2 | Pulmonary surfactant-associated protein A1 | clinvar |
| SFTPC | HGNC:10802 | ENSG00000168484 | P11686 | Surfactant protein C | clinvar |
| TERT | HGNC:11730 | ENSG00000164362 | O14746 | Telomerase reverse transcriptase | clinvar |
| NKX2-1 | HGNC:11825 | ENSG00000136352 | P43699 | Homeobox protein Nkx-2.1 | clinvar |
| HPS4 | HGNC:15844 | ENSG00000100099 | Q9NQG7 | BLOC-3 complex member HPS4 | clinvar |
| RTEL1 | HGNC:15888 | ENSG00000258366 | Q9NZ71 | Regulator of telomere elongation helicase 1 | clinvar |
| TOLLIP | HGNC:16476 | ENSG00000078902 | Q9H0E2 | Toll-interacting protein | clinvar |
| NKD2 | HGNC:17046 | ENSG00000145506 | Q969F2 | Protein naked cuticle homolog 2 | clinvar |
| DTNBP1 | HGNC:17328 | ENSG00000047579 | Q96EV8 | Dysbindin | clinvar |
| SFTA3 | HGNC:18387 | ENSG00000229415 | P0C7M3 | Surfactant-associated protein 3 | clinvar |
| RTKN2 | HGNC:19364 | ENSG00000182010 | Q8IZC4 | Rhotekin-2 | clinvar |
| FAM13A | HGNC:19367 | ENSG00000138640 | O94988 | Protein FAM13A | clinvar |
| EXOC3-AS1 | HGNC:25175 | ENSG00000221990 | Q8N2X6 | Uncharacterized protein EXOC3-AS1 | clinvar |
| CTC1 | HGNC:26169 | ENSG00000178971 | Q2NKJ3 | CST complex subunit CTC1 | clinvar |
| DSP | HGNC:3052 | ENSG00000096696 | P15924 | Desmoplakin | clinvar |
| ABCA3 | HGNC:33 | ENSG00000167972 | Q99758 | Phospholipid-transporting ATPase ABCA3 | clinvar |
| AHRR | HGNC:346 | ENSG00000063438 | A9YTQ3 | Aryl hydrocarbon receptor repressor | clinvar |
| RTEL1-TNFRSF6B | HGNC:44095 | ENSG00000026036 | RTEL1-TNFRSF6B readthrough (NMD candidate) | clinvar | |
| MUC5B-AS1 | HGNC:53936 | ENSG00000255177 | MUC5B antisense RNA 1 | clinvar | |
| IL1RN | HGNC:6000 | ENSG00000136689 | P18510 | Interleukin-1 receptor antagonist protein | clinvar |
| LAMA3 | HGNC:6483 | ENSG00000053747 | Q16787 | Laminin subunit alpha-3 | clinvar |
| LAMA4 | HGNC:6484 | ENSG00000112769 | Q16363 | Laminin subunit alpha-4 | clinvar |
| MMP1 | HGNC:7155 | ENSG00000196611 | P03956 | Interstitial collagenase | clinvar |
| MMP19 | HGNC:7165 | ENSG00000123342 | Q99542 | Matrix metalloproteinase-19 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SFTPA2 | Pulmonary surfactant-associated protein A2 | In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration. |
| MUC5B | Mucin-5B | Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus. |
| SFTPA1 | Pulmonary surfactant-associated protein A1 | In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration. |
| SFTPC | Surfactant protein C | Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. |
| TERT | Telomerase reverse transcriptase | Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. |
| NKX2-1 | Homeobox protein Nkx-2.1 | Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. |
| HPS4 | BLOC-3 complex member HPS4 | Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. |
| RTEL1 | Regulator of telomere elongation helicase 1 | A probable ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. |
| TOLLIP | Toll-interacting protein | Component of the signaling pathway of IL-1 and Toll-like receptors. |
| NKD2 | Protein naked cuticle homolog 2 | Cell autonomous antagonist of the canonical Wnt signaling pathway. |
| DTNBP1 | Dysbindin | Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. |
| SFTA3 | Surfactant-associated protein 3 | Putative surfactant protein. |
| RTKN2 | Rhotekin-2 | May play an important role in lymphopoiesis. |
| CTC1 | CST complex subunit CTC1 | Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. |
| DSP | Desmoplakin | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
| ABCA3 | Phospholipid-transporting ATPase ABCA3 | Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pul… |
| AHRR | Aryl hydrocarbon receptor repressor | Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. |
| IL1RN | Interleukin-1 receptor antagonist protein | Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A. |
| LAMA3 | Laminin subunit alpha-3 | 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. |
| LAMA4 | Laminin subunit alpha-4 | 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. |
| MMP1 | Interstitial collagenase | Cleaves collagens of types I, II, and III at one site in the helical domain. |
| MMP19 | Matrix metalloproteinase-19 | Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). |
Protein-family classification
Druggable: 3 · Difficult: 4 · Unknown: 19 · Druggable fraction: 0.12
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 | 19 | 1.3× | 0.276 |
| Protease | 2 | 2.8× | 0.395 |
| Transporter | 1 | 3.0× | 0.476 |
| Scaffold/PPI | 2 | 1.3× | 0.561 |
| Transcription factor | 2 | 0.6× | 0.840 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SFTPA2 | Other/Unknown | no | C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold | |
| MUC5B | Other/Unknown | no | VWF_dom, VWF_type-D, TIL_dom | |
| SFTPA1 | Other/Unknown | no | C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold | |
| SFTPC | Other/Unknown | no | SP-C, BRICHOS_dom, Surfactant_protein_propep | |
| TERT | Other/Unknown | no | RT_dom, Telomerase_RT, Telomerase_RBD | |
| NKX2-1 | Transcription factor | no | HD, Homeodomain-like_sf, Homeobox_CS | |
| HPS4 | Other/Unknown | no | HPS4, CCZ1/INTU/HSP4_longin_1, CCZ1/INTU/HSP4_longin_3 | |
| RTEL1 | Other/Unknown | no | Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD | |
| TOLLIP | Other/Unknown | no | C2_dom, CUE, UBA-like_sf | |
| NKD2 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, Nkd-like | |
| DTNBP1 | Other/Unknown | no | Dysbindin | |
| SFTA3 | Other/Unknown | no | ||
| RTKN2 | Scaffold/PPI | no | PH_domain, HR1_rho-bd, PH-like_dom_sf | |
| FAM13A | Other/Unknown | no | RhoGAP_dom, Rho_GTPase_activation_prot, FAM13 | |
| EXOC3-AS1 | Other/Unknown | no | ||
| CTC1 | Other/Unknown | no | CTC1, CTC1-like | |
| DSP | Scaffold/PPI | no | Plectin_repeat, SH3_domain, Spectrin/alpha-actinin | |
| ABCA3 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM | |
| AHRR | Transcription factor | no | PAS, bHLH_dom, PAS_fold | |
| RTEL1-TNFRSF6B | Other/Unknown | no | ||
| MUC5B-AS1 | Other/Unknown | no | ||
| IL1RN | Other/Unknown | no | IL-1_fam, IL-1RA/IL-36, IL1/FGF | |
| LAMA3 | Other/Unknown | no | Laminin_IV, EGF, Laminin_G | |
| LAMA4 | Other/Unknown | no | EGF, Laminin_G, LE_dom | |
| MMP1 | Protease | yes | 3.4.24.7 | Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like |
| MMP19 | Protease | yes | Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like |
Expression context
Cohort genes with no expression data: 0.
20 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) | 26 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| right lung | 5 |
| cerebellar hemisphere | 4 |
| right hemisphere of cerebellum | 4 |
| lower lobe of lung | 3 |
| gall bladder | 3 |
| upper lobe of left lung | 3 |
| adult organism | 2 |
| lung | 2 |
| stromal cell of endometrium | 2 |
| left lobe of thyroid gland | 2 |
| right lobe of thyroid gland | 2 |
| thyroid gland | 2 |
| primordial germ cell in gonad | 2 |
| buccal mucosa cell | 2 |
| visceral pleura | 1 |
| mucosa of transverse colon | 1 |
| trachea | 1 |
| olfactory bulb | 1 |
| type B pancreatic cell | 1 |
| cerebellar cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SFTPA2 | 159 | tissue_specific | marker | lower lobe of lung, adult organism, visceral pleura |
| MUC5B | 171 | tissue_specific | marker | trachea, gall bladder, mucosa of transverse colon |
| SFTPA1 | 111 | tissue_specific | marker | right lung, upper lobe of left lung, lung |
| SFTPC | 208 | tissue_specific | marker | lower lobe of lung, right lung, adult organism |
| TERT | 105 | broad | yes | stromal cell of endometrium, type B pancreatic cell, olfactory bulb |
| NKX2-1 | 101 | broad | marker | right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland |
| HPS4 | 261 | ubiquitous | marker | cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex |
| RTEL1 | 134 | ubiquitous | yes | sural nerve, right hemisphere of cerebellum, cerebellar hemisphere |
| TOLLIP | 263 | ubiquitous | marker | right frontal lobe, anterior cingulate cortex, cingulate cortex |
| NKD2 | 130 | broad | yes | upper lobe of left lung, right lung, lung |
| DTNBP1 | 249 | ubiquitous | marker | tendon of biceps brachii, nucleus accumbens, putamen |
| SFTA3 | 107 | tissue_specific | marker | right lobe of thyroid gland, thyroid gland, left lobe of thyroid gland |
| RTKN2 | 152 | ubiquitous | marker | right lung, ventricular zone, primordial germ cell in gonad |
| FAM13A | 293 | ubiquitous | marker | secondary oocyte, oocyte, jejunal mucosa |
| EXOC3-AS1 | 188 | ubiquitous | yes | primordial germ cell in gonad, adenohypophysis, buccal mucosa cell |
| CTC1 | 198 | ubiquitous | marker | granulocyte, right hemisphere of cerebellum, cerebellar hemisphere |
| DSP | 253 | ubiquitous | marker | skin of hip, upper leg skin, hair follicle |
| ABCA3 | 222 | ubiquitous | marker | lower lobe of lung, upper lobe of lung, upper lobe of left lung |
| AHRR | 131 | ubiquitous | yes | left testis, stromal cell of endometrium, right testis |
| RTEL1-TNFRSF6B | 135 | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellum | |
| MUC5B-AS1 | 85 | yes | colonic epithelium, gall bladder, tonsil | |
| IL1RN | 220 | broad | marker | lower esophagus mucosa, buccal mucosa cell, palpebral conjunctiva |
| LAMA3 | 239 | broad | marker | right lung, skin of leg, skin of abdomen |
| LAMA4 | 268 | ubiquitous | marker | lower esophagus muscularis layer, lower esophagus, nerve |
| MMP1 | 172 | broad | marker | epithelial cell of pancreas, pancreatic ductal cell, islet of Langerhans |
| MMP19 | 222 | ubiquitous | marker | left uterine tube, gall bladder, omental fat pad |
Protein interactions among cohort
Intra-cohort edges: 11.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TERT | 5,717 |
| MMP1 | 2,933 |
| DSP | 2,897 |
| LAMA4 | 2,688 |
| MUC5B | 2,659 |
| IL1RN | 2,550 |
| TOLLIP | 2,543 |
| NKX2-1 | 2,403 |
| RTEL1 | 2,324 |
| LAMA3 | 2,195 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ABCA3 | NKX2-1 | string_interaction |
| ABCA3 | RTEL1 | string_interaction |
| ABCA3 | SFTPC | string_interaction |
| CTC1 | RTEL1 | string_interaction |
| CTC1 | TERT | string_interaction |
| DTNBP1 | HPS4 | string_interaction |
| FAM13A | RTEL1 | biogrid_interaction |
| FAM13A | RTEL1-TNFRSF6B | intact |
| MUC5B | SFTPC | string_interaction |
| NKX2-1 | SFTPC | string_interaction |
| RTEL1 | TERT | string_interaction |
Structural data
PDB: 13 · AlphaFold-only: 11 · No structure: 2
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TERT | O14746 | 23 |
| MMP1 | P03956 | 15 |
| CTC1 | Q2NKJ3 | 7 |
| IL1RN | P18510 | 5 |
| DSP | P15924 | 4 |
| SFTPC | P11686 | 3 |
| RTEL1 | Q9NZ71 | 3 |
| MUC5B | Q9HC84 | 2 |
| NKX2-1 | P43699 | 2 |
| TOLLIP | Q9H0E2 | 2 |
| ABCA3 | Q99758 | 2 |
| HPS4 | Q9NQG7 | 1 |
| AHRR | A9YTQ3 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SFTPA2 | Q8IWL1 | 84.09 |
| SFTPA1 | Q8IWL2 | 83.15 |
| MMP19 | Q99542 | 79.70 |
| DTNBP1 | Q96EV8 | 75.92 |
| LAMA4 | Q16363 | 73.75 |
| RTKN2 | Q8IZC4 | 70.33 |
| SFTA3 | P0C7M3 | 61.17 |
| FAM13A | O94988 | 61.00 |
| NKD2 | Q969F2 | 56.15 |
| EXOC3-AS1 | Q8N2X6 | 50.37 |
| LAMA3 | Q16787 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 99. Enrichment computed across 26 evidence-associated genes (20 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 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective CSF2RB causes SMDP5 | 4 | 326.3× | 1e-08 | SFTPA2, SFTPA1, SFTPC, SFTA3 |
| Defective CSF2RA causes SMDP4 | 4 | 326.3× | 1e-08 | SFTPA2, SFTPA1, SFTPC, SFTA3 |
| Surfactant metabolism | 5 | 92.1× | 5e-08 | SFTPA2, SFTPA1, SFTPC, SFTA3, ABCA3 |
| Diseases associated with surfactant metabolism | 3 | 428.2× | 5e-07 | SFTPA2, SFTPA1, ABCA3 |
| Diseases of metabolism | 4 | 16.1× | 0.002 | SFTPA2, MUC5B, SFTPA1, ABCA3 |
| Extracellular matrix organization | 4 | 12.6× | 0.004 | LAMA3, LAMA4, MMP1, MMP19 |
| Signal regulatory protein family interactions | 2 | 67.2× | 0.005 | SFTPA2, SFTPA1 |
| Cell-Cell communication | 3 | 20.6× | 0.005 | SFTPA2, SFTPA1, LAMA3 |
| Extension of Telomeres | 2 | 60.1× | 0.005 | TERT, RTEL1 |
| MET promotes cell motility | 2 | 60.1× | 0.005 | LAMA3, LAMA4 |
| Degradation of the extracellular matrix | 3 | 17.7× | 0.005 | LAMA3, MMP1, MMP19 |
| Regulation of TLR by endogenous ligand | 2 | 49.6× | 0.005 | SFTPA2, SFTPA1 |
| Attachment of bacteria to epithelial cells | 2 | 49.6× | 0.005 | LAMA3, LAMA4 |
| Telomere Extension By Telomerase | 2 | 45.7× | 0.006 | TERT, RTEL1 |
| Laminin interactions | 2 | 38.1× | 0.008 | LAMA3, LAMA4 |
| MET activates PTK2 signaling | 2 | 38.1× | 0.008 | LAMA3, LAMA4 |
| Telomere Maintenance | 2 | 36.8× | 0.008 | TERT, RTEL1 |
| Defective ABCA3 causes SMDP3 | 1 | 571.0× | 0.008 | ABCA3 |
| Defective SFTPA2 causes IPF | 1 | 571.0× | 0.008 | SFTPA2 |
| Defective pro-SFTPC causes SMDP2 and RDS | 1 | 571.0× | 0.008 | SFTPC |
| Signaling by MET | 2 | 31.7× | 0.008 | LAMA3, LAMA4 |
| Formation of the dystrophin-glycoprotein complex (DGC) | 2 | 30.9× | 0.008 | LAMA3, LAMA4 |
| Developmental Lineage of Pancreatic Ductal Cells | 2 | 22.8× | 0.014 | LAMA3, LAMA4 |
| Chromosome Maintenance | 2 | 21.1× | 0.016 | TERT, RTEL1 |
| Collagen degradation | 2 | 17.6× | 0.021 | MMP1, MMP19 |
| Toll Like Receptor 2 (TLR2) Cascade | 2 | 17.3× | 0.021 | SFTPA2, SFTPA1 |
| Toll Like Receptor TLR1:TLR2 Cascade | 2 | 16.8× | 0.022 | SFTPA2, SFTPA1 |
| Non-integrin membrane-ECM interactions | 2 | 15.4× | 0.025 | LAMA3, LAMA4 |
| ECM proteoglycans | 2 | 15.0× | 0.025 | LAMA3, LAMA4 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| respiratory gaseous exchange by respiratory system | 3 | 81.4× | 0.001 | SFTPA2, SFTPA1, SFTPC |
| telomere maintenance | 3 | 34.9× | 0.009 | TERT, RTEL1, CTC1 |
| replicative senescence | 2 | 86.2× | 0.017 | TERT, CTC1 |
| DNA strand displacement | 1 | 732.7× | 0.021 | RTEL1 |
| RNA-templated transcription | 1 | 732.7× | 0.021 | TERT |
| DNA strand elongation | 1 | 732.7× | 0.021 | TERT |
| positive regulation of protein homooligomerization | 1 | 732.7× | 0.021 | ABCA3 |
| positive regulation of eye pigmentation | 1 | 732.7× | 0.021 | HPS4 |
| siRNA transcription | 1 | 732.7× | 0.021 | TERT |
| positive regulation of transdifferentiation | 1 | 732.7× | 0.021 | TERT |
| negative regulation of telomere maintenance in response to DNA damage | 1 | 732.7× | 0.021 | RTEL1 |
| positive regulation of telomeric loop disassembly | 1 | 732.7× | 0.021 | RTEL1 |
| platelet dense granule organization | 2 | 58.6× | 0.021 | HPS4, DTNBP1 |
| response to hormone | 2 | 37.6× | 0.021 | NKX2-1, MMP19 |
| collagen catabolic process | 2 | 34.1× | 0.022 | MMP1, MMP19 |
| RNA-templated DNA biosynthetic process | 1 | 366.4× | 0.023 | TERT |
| developmental induction | 1 | 366.4× | 0.023 | NKX2-1 |
| positive regulation of hair cycle | 1 | 366.4× | 0.023 | TERT |
| Golgi vesicle fusion to target membrane | 1 | 366.4× | 0.023 | NKD2 |
| positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization | 1 | 366.4× | 0.023 | DTNBP1 |
| telomeric loop disassembly | 1 | 366.4× | 0.023 | RTEL1 |
| regulation of phosphatidylcholine metabolic process | 1 | 366.4× | 0.023 | ABCA3 |
| extracellular matrix disassembly | 2 | 31.9× | 0.023 | MMP1, MMP19 |
| regulation of embryonic development | 2 | 28.7× | 0.023 | LAMA3, LAMA4 |
| response to glucocorticoid | 2 | 28.2× | 0.023 | ABCA3, IL1RN |
| regulation of cell adhesion | 2 | 26.6× | 0.023 | LAMA3, LAMA4 |
| cerebral cortex GABAergic interneuron differentiation | 1 | 244.2× | 0.029 | NKX2-1 |
| xenobiotic export from cell | 1 | 244.2× | 0.029 | ABCA3 |
| negative regulation of single-species biofilm formation in or on host organism | 1 | 244.2× | 0.029 | MUC5B |
| mitotic telomere maintenance via semi-conservative replication | 1 | 244.2× | 0.029 | RTEL1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 24
Druggability breadth: 7 of 26 evidence-associated genes (27%) 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 |
| MMP1 | TILUDRONATE DISODIUM |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MMP1 | 21 | 4 |
| TERT | 10 | 4 |
| SFTPA2 | 0 | 0 |
| MUC5B | 0 | 0 |
| SFTPA1 | 0 | 0 |
| SFTPC | 0 | 0 |
| NKX2-1 | 0 | 0 |
| HPS4 | 0 | 0 |
| RTEL1 | 0 | 0 |
| TOLLIP | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| BERBERINE | 4 | TERT |
| DOXORUBICIN | 4 | TERT |
| TILUDRONATE DISODIUM | 4 | MMP1 |
| PRAZOSIN | 4 | MMP1 |
| SULFASALAZINE | 4 | MMP1 |
| IRINOTECAN | 4 | MMP1 |
| NIMESULIDE | 4 | MMP1 |
| DOXAZOSIN | 4 | MMP1 |
| RESVERATROL | 3 | TERT |
| EPIGALOCATECHIN GALLATE | 3 | MMP1, TERT |
| PERIFOSINE | 3 | TERT |
| CAFFEIC ACID | 3 | MMP1 |
| MARIMASTAT | 3 | MMP1 |
| QUERCETIN | 3 | MMP1 |
| PRINOMASTAT | 3 | MMP1 |
| ISOMETAMIDIUM | 2 | TERT |
| HOMIDIUM BROMIDE | 2 | TERT |
| ALLICIN | 2 | TERT |
| OLEIC ACID | 2 | TERT |
| ETHACRIDINE | 2 | TERT |
| CIPEMASTAT | 2 | MMP1 |
| ILOMASTAT | 2 | MMP1 |
| APRATASTAT | 2 | MMP1 |
| SOLIMASTAT | 2 | MMP1 |
| TANOMASTAT | 2 | MMP1 |
| BATIMASTAT | 2 | MMP1 |
| (+)-SECOISOLARICIRESINOL | 2 | MMP1 |
| CTS-1027 | 2 | MMP1 |
| REBIMASTAT | 2 | MMP1 |
| AMINOQUINURIDE | 2 | MMP1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| MMP1 | 588 | Binding:574, ADMET:10, Functional:3, Toxicity:1 |
| TERT | 391 | Binding:389, Functional:2 |
| IL1RN | 26 | Binding:26 |
| MMP19 | 4 | ADMET:2, Binding:1, Toxicity:1 |
| DSP | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| MMP1 | 3.4.24.7 | interstitial collagenase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| TERT | 391 |
| MMP1 | 588 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 23; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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 |
| TILUDRONATE DISODIUM | 4 | MMP1 |
| PRAZOSIN | 4 | MMP1 |
| SULFASALAZINE | 4 | MMP1 |
| IRINOTECAN | 4 | MMP1 |
| NIMESULIDE | 4 | MMP1 |
| DOXAZOSIN | 4 | MMP1 |
| RESVERATROL | 3 | TERT |
| EPIGALOCATECHIN GALLATE | 3 | MMP1, TERT |
| PERIFOSINE | 3 | TERT |
| CAFFEIC ACID | 3 | MMP1 |
| MARIMASTAT | 3 | MMP1 |
| QUERCETIN | 3 | MMP1 |
| PRINOMASTAT | 3 | MMP1 |
| ISOMETAMIDIUM | 2 | TERT |
| HOMIDIUM BROMIDE | 2 | TERT |
| ALLICIN | 2 | TERT |
| OLEIC ACID | 2 | TERT |
| ETHACRIDINE | 2 | TERT |
| CIPEMASTAT | 2 | MMP1 |
| ILOMASTAT | 2 | MMP1 |
| APRATASTAT | 2 | MMP1 |
| SOLIMASTAT | 2 | MMP1 |
| TANOMASTAT | 2 | MMP1 |
| BATIMASTAT | 2 | MMP1 |
| (+)-SECOISOLARICIRESINOL | 2 | MMP1 |
| CTS-1027 | 2 | MMP1 |
| REBIMASTAT | 2 | MMP1 |
| AMINOQUINURIDE | 2 | MMP1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | TERT, MMP1 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | ABCA3 |
| D | Druggable family + AlphaFold only, no drug | 1 | MMP19 |
| E | Difficult family or no structure, no drug | 22 | SFTPA2, MUC5B, SFTPA1, SFTPC, NKX2-1, HPS4, RTEL1, TOLLIP, NKD2, DTNBP1 (+12 more) |
Undrugged target profiles
24 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| SFTPA2 | 0 | — |
| MUC5B | 0 | — |
| SFTPA1 | 0 | — |
| SFTPC | 0 | — |
| NKX2-1 | 0 | — |
| HPS4 | 0 | — |
| RTEL1 | 0 | — |
| TOLLIP | 0 | — |
| NKD2 | 0 | — |
| DTNBP1 | 0 | — |
| SFTA3 | 0 | — |
| RTKN2 | 0 | — |
| FAM13A | 0 | — |
| EXOC3-AS1 | 0 | — |
| CTC1 | 0 | — |
| DSP | 2 | — |
| ABCA3 | 0 | — |
| AHRR | 0 | — |
| RTEL1-TNFRSF6B | 0 | — |
| MUC5B-AS1 | 0 | — |
| IL1RN | 26 | — |
| LAMA3 | 0 | — |
| LAMA4 | 0 | — |
| MMP19 | 4 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 2.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06644144 | Not specified | RECRUITING | P4O2 ILD Extension |
| NCT06372353 | Not specified | COMPLETED | The Effect Of Baduanjin Exercises In Patients With Idiopathic Pulmonary Fibrosis |