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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SFTPC
surfactant protein C
Chromosome 8 Β· 8p21.3
NCBI Gene: 6440Ensembl: ENSG00000168484.13HGNC: HGNC:10802UniProt: A0A0S2Z4Q0
139PubMed Papers
21Diseases
0Drugs
28Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
identical protein bindingprotein bindingalveolar lamellar bodyGO:0005615Congenital pulmonary alveolar proteinosissurfactant metabolism dysfunction, pulmonary, 2hereditary pulmonary alveolar proteinosisinterstitial lung disease
✦AI Summary

SFTPC (surfactant protein C) is a pulmonary surfactant protein synthesized by alveolar type 2 (AT2) cells that reduces surface tension at the air-liquid interface in alveoli, promoting alveolar stability 1. AT2 cells expressing SFTPC function as long-term alveolar stem cells capable of self-renewal and differentiation into AT1 cells over extended periods 1. SFTPC+ cells maintain alveolar homeostasis through metabolically active surfactant biosynthesis and serve as facultative progenitors for alveolar epithelial regeneration 2. In disease pathology, SFTPC mutations contribute to pulmonary surfactant metabolism dysfunction and pulmonary fibrosis susceptibility 3. AT2 cell dysfunction involving compromised SFTPC processing, impaired quality control mechanisms (unfolded protein response, autophagy, proteasome degradation), and ferroptosis drives the pathophysiology of idiopathic pulmonary fibrosis and COPD 45. Clinically, SFTPC gene variants represent heritable risk factors for progressive fibrotic lung disease with prognostic implications 3. Patient-derived AT2 cells with SFTPC mutations can be corrected using CRISPR-Cas9 gene editing, restoring surfactant processing and providing platforms for disease modeling and potential regenerative therapies 26. These advances highlight SFTPC's critical role in alveolar maintenance and its therapeutic potential as a target for precision medicine in pulmonary fibrosis and obstructive lung diseases.

Sources cited
1
SFTPC+ AT2 cells are long-term alveolar stem cells capable of self-renewal and differentiation; they expand clonally upon injury and form alveolospheres with stromal support
PMID: 23921127
2
Human PSC-derived SFTPC+ AEC2s are facultative progenitors displaying self-renewal and functional capacity; CRISPR correction of SFTPB mutations in patient-derived cells restores surfactant processing
PMID: 28965766
3
AT2 cells are metabolically active for surfactant biosynthesis and alveolar homeostasis; failed quality control mechanisms result in ER stress, autophagy defects, and fibrotic signaling in IPF
PMID: 32870817
4
SFTPC genetic variants are heritable contributors to pulmonary fibrosis with implications for disease progression, prognosis, and treatment response; SFTPC is among key genes in telomere biology pathways
PMID: 38573068
5
SFTPC+ alveolar epithelial cells undergo ferroptosis in COPD pathogenesis; HIF-3Ξ±-GPx4 axis activation in these cells prevents ferroptosis and COPD progression
PMID: 39310101
6
SFTPC gene editing in lung tissue achieves 19% average efficiency using thermostable Cas9 RNP-LNP complexes, representing significant improvement for therapeutic genome editing
PMID: 39415058
7
SFTPC+ hiPSC-derived AT2 cells establish stable alveolar organoids with self-renewal capacity, appropriate transcriptomes, and ability to differentiate into AT1-like cells for disease modeling
PMID: 28967890
Disease Associationsβ“˜21
Congenital pulmonary alveolar proteinosisOpen Targets
0.71Strong
surfactant metabolism dysfunction, pulmonary, 2Open Targets
0.68Moderate
hereditary pulmonary alveolar proteinosisOpen Targets
0.52Moderate
interstitial lung diseaseOpen Targets
0.47Moderate
idiopathic pulmonary fibrosisOpen Targets
0.38Weak
newborn respiratory distress syndromeOpen Targets
0.38Weak
pulmonary alveolar proteinosisOpen Targets
0.37Weak
chronic respiratory distress with surfactant metabolism deficiencyOpen Targets
0.37Weak
genetic disorderOpen Targets
0.27Weak
pulmonary fibrosisOpen Targets
0.17Weak
Neonatal acute respiratory distress with surfactant metabolism deficiencyOpen Targets
0.13Weak
surfactant metabolism dysfunction, pulmonary, 1Open Targets
0.13Weak
neoplasmOpen Targets
0.10Weak
non-small cell lung carcinomaOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
Abruptio PlacentaeOpen Targets
0.08Suggestive
infectionOpen Targets
0.06Suggestive
lung carcinomaOpen Targets
0.05Suggestive
Respiratory Syncytial Virus InfectionOpen Targets
0.05Suggestive
primary ciliary dyskinesiaOpen Targets
0.05Suggestive
Pulmonary surfactant metabolism dysfunction 2UniProt
Pathogenic Variants28
NM_001317778.2(SFTPC):c.218T>C (p.Ile73Thr)Pathogenic
Surfactant metabolism dysfunction, pulmonary, 2|not provided|Hereditary pulmonary alveolar proteinosis|Pulmonary fibrosis
β˜…β˜…β˜†β˜†2026β†’ Residue 73
NM_001317778.2(SFTPC):c.435+2T>CPathogenic
not provided|Surfactant metabolism dysfunction, pulmonary, 2
β˜…β˜…β˜†β˜†2025
NM_001317778.2(SFTPC):c.329T>C (p.Leu110Pro)Pathogenic
Hereditary pulmonary alveolar proteinosis|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 110
NM_001317778.2(SFTPC):c.163C>T (p.Leu55Phe)Likely pathogenic
SFTPC-related disorder|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 55
NM_001317778.2(SFTPC):c.325-1G>CPathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_001317778.2(SFTPC):c.400del (p.Glu135fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 135
NM_001317778.2(SFTPC):c.435+1G>APathogenic
Surfactant metabolism dysfunction, pulmonary, 2|not provided
β˜…β˜†β˜†β˜†2024
NM_001317778.2(SFTPC):c.314A>G (p.Asp105Gly)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 105
NM_001317778.2(SFTPC):c.325-1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_001317778.2(SFTPC):c.313G>T (p.Asp105Tyr)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 105
NM_001317778.2(SFTPC):c.314A>T (p.Asp105Val)Likely pathogenic
Surfactant metabolism dysfunction, pulmonary, 2
β˜…β˜†β˜†β˜†2022β†’ Residue 105
NM_001317778.2(SFTPC):c.481C>T (p.Arg161Ter)Likely pathogenic
Surfactant metabolism dysfunction, pulmonary, 2
β˜…β˜†β˜†β˜†2021β†’ Residue 161
NM_001317778.2(SFTPC):c.444del (p.Ala149fs)Likely pathogenic
Surfactant metabolism dysfunction, pulmonary, 2
β˜…β˜†β˜†β˜†2021β†’ Residue 149
NM_001317778.2(SFTPC):c.334G>C (p.Ala112Pro)Likely pathogenic
Hereditary pulmonary alveolar proteinosis
β˜…β˜†β˜†β˜†2020β†’ Residue 112
NM_001317778.2(SFTPC):c.316T>C (p.Tyr106His)Likely pathogenic
Interstitial lung disease 2
β˜…β˜†β˜†β˜†2019β†’ Residue 106
NM_001317778.2(SFTPC):c.435G>A (p.Gln145=)Likely pathogenic
Hereditary pulmonary alveolar proteinosis
β˜…β˜†β˜†β˜†2018β†’ Residue 145
NM_001317778.2(SFTPC):c.337T>C (p.Tyr113His)Likely pathogenic
Hereditary pulmonary alveolar proteinosis
β˜…β˜†β˜†β˜†2018β†’ Residue 113
NM_001317778.2(SFTPC):c.413_430delinsAGGTGATC (p.Thr138fs)Pathogenic
Hereditary pulmonary alveolar proteinosis
β˜…β˜†β˜†β˜†2017β†’ Residue 138
NM_001317778.2(SFTPC):c.397A>C (p.Ser133Arg)Likely pathogenic
Inborn genetic diseases|Surfactant metabolism dysfunction, pulmonary, 2
β˜…β˜†β˜†β˜†2017β†’ Residue 133
NM_001317778.2(SFTPC):c.476_477del (p.Glu159fs)Likely pathogenic
Hereditary pulmonary alveolar proteinosis
β˜…β˜†β˜†β˜†2017β†’ Residue 159
View on ClinVar β†—
Related Genes
SFTPA2Protein interaction99%AQP5Protein interaction95%FOXJ1Protein interaction95%SCGB3A2Protein interaction95%SCGB1A1Protein interaction95%TTF1Protein interaction91%
Tissue Expression6 tissues
Lung
100%
Brain
0%
Liver
0%
Ovary
0%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
SFTPCSFTPA2AQP5FOXJ1SCGB3A2SCGB1A1TTF1
PROTEIN STRUCTURE
Preparing viewer…
PDB2YAD Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.00LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.40–1.00]
RankingsWhere SFTPC stands among ~20K protein-coding genes
  • #3,323of 20,598
    Most Researched139 Β· top quartile
  • #1,868of 5,498
    Most Pathogenic Variants28
  • #9,653of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedSFTPC
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Type 2 alveolar cells are stem cells in adult lung.
PMID: 23921127
J Clin Invest Β· 2013
1.00
2
Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells.
PMID: 28965766
Cell Stem Cell Β· 2017
0.90
3
Contributions of alveolar epithelial cell quality control to pulmonary fibrosis.
PMID: 32870817
J Clin Invest Β· 2020
0.80
4
Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.
PMID: 38573068
Am J Respir Crit Care Med Β· 2024
0.70
5
S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells suppress ferroptosis and alleviate radiation-induced lung injury and long-term pulmonary fibrosis.
PMID: 39462403
J Nanobiotechnology Β· 2024
0.60