Characteristics of genes involved in monogenic parenchymal lung disease

 Genomic location10q22.310q22.32p11.28p21.316p13.314q13.3
 Size kb4.
 Number of exons (coding)6 (4)6 (4)11 (10)6 (5)33 (30)3 (3)
 Exons encoding mature protein3–63–66–724–331–3
 Number of amino acids in mature protein (numbering)227 (21–248)227 (21–248)79 (201–279)35 (24–58)1704 (1–1704)401 (1–401)
 Molecular weight of mature protein kDa35358419139
 InheritanceAutosomal dominantAutosomal dominantAutosomal recessiveAutosomal dominantAutosomal recessiveAutosomal dominant
 Children at diagnosisRare (one infant)Not reportedNeonatal RDS
Rarely ILD in childhood
ILD in childhood
Some neonatal RDS
Neonatal RDS
ILD in childhood
Neonatal RDS
ILD in childhood
 Adults at diagnosisInterstitial pneumonitis/pulmonary fibrosis
Lung cancer
Interstitial pneumonitis/pulmonary fibrosis
Lung cancer
Not reportedInterstitial pneumonitis/pulmonary fibrosisRarely
Interstitial pneumonitis/pulmonary fibrosis
Interstitial pneumonitis/pulmonary fibrosis
 Mutation sitesCRDCRDCoding sequenceMature peptide
C-terminal linker
BRICHOS domain
Coding sequenceGene deletion
Exon 2–3
Most frequent mutation
 Known asNANA121ins2I73TE292VNA
 DNA notationc.361delCinsGAA#c.218T>Cc.875A>T
 RS numberrs35328240rs121917834rs149989682
 Mutation frequency>60% of mutated alleles>25% of mutated alleles<10% of mutated alleles
 OriginHaplotype of NW European descentMutation hotspotUnique haplotype associated with European descent
 GnomAD allele frequency0.0004+0.0000.004

RDS: respiratory distress syndrome; ILD: interstitial lung disease; CRD: carbohydrate recognition domain; NA: not applicable; NW: North-Western. #: depending on the transcript referred to as c.397delCinsGAA and p.Pro133GlnfsTer95; : GnomAD frequency for European non-Finnish; +: frequency of rs779795233, the read data shows this concerns rs35328240.