Idiopathic pulmonary fibrosis: genes and variants

Genes linked to Idiopathic pulmonary fibrosis

• TERT: Telomerase reverse transcriptase

  It extends telomeric DNA using an internal RNA template and helps counter progressive chromosome-end shortening in stem and proliferative cells. Loss-of-function variants cause telomere-biology disorders, while promoter activation and increased activity support unlimited proliferation in many cancers.

  13 disease-causing and 1,078 uncertain variants in TERT are linked to Idiopathic pulmonary fibrosis.

• DSP: Desmoplakin

  It anchors intermediate filaments to desmosomes, allowing mechanically stressed tissues such as myocardium and epidermis to maintain strong cell-cell adhesion. Pathogenic variants can cause arrhythmogenic or dilated cardiomyopathy and a range of cardiocutaneous disorders.

  0 disease-causing and 0 uncertain variants in DSP are linked to Idiopathic pulmonary fibrosis.

• FGFR1: Fibroblast growth factor receptor 1

  Its fibroblast-growth-factor signaling controls proliferation, differentiation, migration, and developmental patterning in many tissues. Germline pathogenic variants can cause hypogonadotropic hypogonadism or craniosynostosis syndromes, while fusions and other activating alterations drive selected cancers.

  0 disease-causing and 0 uncertain variants in FGFR1 are linked to Idiopathic pulmonary fibrosis.

• FGFR4: Fibroblast growth factor receptor 4

  It transmits fibroblast-growth-factor signals involved in metabolism, tissue repair, development, and cell proliferation, with FGF19 as an important metabolic ligand. Aberrant signaling can support tumor growth, and activating alterations are therapeutic targets in selected cancers.

  0 disease-causing and 0 uncertain variants in FGFR4 are linked to Idiopathic pulmonary fibrosis.

• PDGFRA: Platelet-derived growth factor receptor alpha

  PDGF signaling through this pathway promotes proliferation, survival, and migration of mesenchymal progenitors. Activating mutations or fusions drive gastrointestinal stromal tumors and selected hematologic and solid malignancies and can create kinase-inhibitor sensitivity.

  0 disease-causing and 0 uncertain variants in PDGFRA are linked to Idiopathic pulmonary fibrosis.

• PDGFRB: Platelet-derived growth factor receptor beta

  Its signaling supports pericytes, vascular smooth-muscle cells, and other mesenchymal lineages during growth and tissue repair. Oncogenic fusions drive myeloid neoplasms, while germline activating or loss-of-function variants can cause developmental and vascular disorders.

  0 disease-causing and 0 uncertain variants in PDGFRB are linked to Idiopathic pulmonary fibrosis.

• SFTPC: Surfactant protein C

  It contributes to pulmonary surfactant organization and is produced specifically by alveolar type II cells. Dominant pathogenic variants can cause interstitial lung disease across infancy and adulthood, often through protein misfolding and toxic cellular stress.

  0 disease-causing and 0 uncertain variants in SFTPC are linked to Idiopathic pulmonary fibrosis.

Weakly linked (only a few uncertain records): ABCA3.

Where Idiopathic pulmonary fibrosis variants cluster

• TERT Reverse transcriptase (positions 605–935): 7 of 13 disease-causing changes, 1.8× more than its size predicts.

Known disease-causing variants in Idiopathic pulmonary fibrosis

Which prediction tools work for Idiopathic pulmonary fibrosis

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 72 out of 100
• CADD: 68 out of 100
• phyloP: 57 out of 100

Same protein, different disease

• Dyskeratosis congenita is also caused by TERT variants; they fall partly in the same places as the Idiopathic pulmonary fibrosis variants (23 disease-causing).
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 is also caused by TERT variants; they fall partly in the same places as the Idiopathic pulmonary fibrosis variants (13 disease-causing).

Diseases related to Idiopathic pulmonary fibrosis

• Interstitial lung disease, also linked to FGFR1, FGFR4, PDGFRA, PDGFRB and 2 more
• Non-small cell lung carcinoma, also linked to FGFR1, FGFR4, PDGFRA and PDGFRB
• Acute myeloid leukemia, also linked to PDGFRA, PDGFRB and TERT
• Colorectal cancer, also linked to FGFR1, PDGFRA and PDGFRB
• Renal cell carcinoma, also linked to FGFR1, PDGFRA and PDGFRB
• Gastrointestinal stromal tumor, also linked to PDGFRA and PDGFRB
• Hepatocellular carcinoma, also linked to PDGFRB and TERT
• Hypertrophic cardiomyopathy, also linked to DSP
• Dilated cardiomyopathy, also linked to DSP
• Cardiac arrhythmia, also linked to DSP
• Hypogonadotropic hypogonadism 2 with or without anosmia, also linked to FGFR1
• Ovarian cancer, also linked to PDGFRA

Frequently asked questions

Which genes are linked to Idiopathic pulmonary fibrosis?

In CATVariant, Idiopathic pulmonary fibrosis is linked to 7 analyzed proteins: TERT (Telomerase reverse transcriptase), DSP (Desmoplakin), FGFR1 (Fibroblast growth factor receptor 1), FGFR4 (Fibroblast growth factor receptor 4), PDGFRA (Platelet-derived growth factor receptor alpha), PDGFRB (Platelet-derived growth factor receptor beta) and 1 more.

How many genetic variants are linked to Idiopathic pulmonary fibrosis?

1,143 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1,078 are of uncertain significance or have conflicting reports.

Which uncertain variants in Idiopathic pulmonary fibrosis look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Idiopathic pulmonary fibrosis?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.71, based on 12 disease-causing and 298 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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