TABLE 1

Main genes with rare variants associated with pulmonary fibrosis

FunctionGeneTransmissionAge of onset of pulmonary manifestationAssociated signs
TelomeraseTERT-TERCADAdults, average 55 yearsTelomeropathy;
combined pulmonary fibrosis and emphysema
TINF2ADChildren, rare adults <50 yearsTelomeropathy [31]
DKC1XChildren, rare adults <50 yearsTelomeropathy [120]
HelicaseRTEL1ADAdults 35–60 yearsTelomeropathy
RNA regulationPARNADAdults 47–81 yearsPulmonary granulomatosis;
telomeropathy [33]
NAF1ADAdults 45–60 yearsTelomeropathy [5]
SurfactantSFTPA1-SFTPA2ADFrom newborn to 72 yearsLung cancer [90, 121]
SFTPBARNewborn[122]
SFTPCADChildren, rare adults <50 yearsCombined pulmonary fibrosis and emphysema [123]
ABCA3ARChildren, rare adults <50 yearsCombined pulmonary fibrosis and emphysema [83]
NFKX2-1 (TITF1)ADChildren, rare adults <50 yearsChorea, hypothyroidism [93]
Tumour suppressorNF1ADAdultsType 1 neurofibromatosis [124]
LysosomeHPS-1 to HPS-8/AP-3B1ARAdultsHermansky–Pudlak syndrome [125]
Stimulation of interferon synthesisTMEM173ADChildren, rare adults <50 yearsRecurrent fever;
alopecia; skin rash;
antinuclear antibodies;
vasculitis [95, 100]
Endoplasmic reticulum stressCOPAADChildren, rare adults <25 yearsArthritis, antinuclear antibodies and ANCA [8]
UnknownFAM111BAD7–30 yearsMyopathy, poikiloderma [6]
MitochondriaNDUFAF6AR19–50 yearsAcadian variant of Fanconi syndrome [126]
Zinc finger transcription factorsGATA2AD4–76 yearsAlveolar proteinosis;
myeloid disease;
monoMAC syndrome [10]

  • AD: autosomal dominant; X: X-linked; AR: autosomal recessive; ANCA: anti-neutrophil cytoplasmic antibodies.