Characteristics of genes involved in monogenic parenchymal lung disease
| Characteristic | SFTPA1 | SFTPA2 | SFTPB | SFTPC | ABCA3 | NKX2-1 |
| Genomic | ||||||
| Genomic location | 10q22.3 | 10q22.3 | 2p11.2 | 8p21.3 | 16p13.3 | 14q13.3 |
| Size kb | 4.5 | 4.5 | 9.5 | 9.8 | 65 | 3.8 |
| Number of exons (coding) | 6 (4) | 6 (4) | 11 (10) | 6 (5) | 33 (30) | 3 (3) |
| Exons encoding mature protein | 3–6 | 3–6 | 6–7 | 2 | 4–33 | 1–3 |
| 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 kDa | 35 | 35 | 8 | 4 | 191 | 39 |
| Disease | ||||||
| Inheritance | Autosomal dominant | Autosomal dominant | Autosomal recessive | Autosomal dominant | Autosomal recessive | Autosomal dominant |
| Children at diagnosis | Rare (one infant) | Not reported | Neonatal RDS Rarely ILD in childhood | ILD in childhood Some neonatal RDS | Neonatal RDS ILD in childhood | Neonatal RDS ILD in childhood |
| Adults at diagnosis | Interstitial pneumonitis/pulmonary fibrosis Lung cancer | Interstitial pneumonitis/pulmonary fibrosis Lung cancer | Not reported | Interstitial pneumonitis/pulmonary fibrosis | Rarely Interstitial pneumonitis/pulmonary fibrosis | Rarely Interstitial pneumonitis/pulmonary fibrosis |
| Mutation sites | CRD | CRD | Coding sequence | Mature peptide C-terminal linker BRICHOS domain | Coding sequence | Gene deletion Exon 2–3 |
| Most frequent mutation | ||||||
| Known as | NA | NA | 121ins2 | I73T | E292V | NA |
| DNA notation | c.361delCinsGAA# | c.218T>C | c.875A>T | |||
| Protein | p.(Pro121GlufsTer95)# | p.(Ile73Thr) | p.(Glu292Val) | |||
| Transcript | NM_000542.5 | NM_003018.3 | NM_001089.3 | |||
| RS number | rs35328240 | rs121917834 | rs149989682 | |||
| Classification | Pathogenic | Pathogenic | Pathogenic | |||
| Mutation frequency | >60% of mutated alleles | >25% of mutated alleles | <10% of mutated alleles | |||
| Origin | Haplotype of NW European descent | Mutation hotspot | Unique haplotype associated with European descent | |||
| GnomAD allele frequency¶ | 0.0004+ | 0.000 | 0.004 |
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.