SFTPA1

Summary

SFTPA1 (surfactant protein A1, HGNC:10798) is a protein-coding gene on chromosome 10q22.3, encoding Pulmonary surfactant-associated protein A1 (Q8IWL2). In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration.

This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 653509 — RefSeq curated summary.

At a glance

• Gene–disease (curated): interstitial lung disease 1 (Strong, GenCC)
• Clinical variants (ClinVar): 107 total — 4 pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_005411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10798
Approved symbol	SFTPA1
Name	surfactant protein A1
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	SP-A, SP-A1, COLEC4
Ensembl gene	ENSG00000122852
Ensembl biotype	protein_coding
OMIM	178630
Entrez	653509

Gene structure

Transcript identifiers

Ensembl transcripts: 189 — 188 protein_coding, 1 retained_intron

ENST00000398636, ENST00000419470, ENST00000428376, ENST00000429958, ENST00000486922, ENST00000895517, ENST00000895518, ENST00000895519, ENST00000895520, ENST00000895521, ENST00000895522, ENST00000895523, ENST00000895524, ENST00000895525, ENST00000895526, ENST00000895527, ENST00000895528, ENST00000895529, ENST00000895530, ENST00000895531, ENST00000895532, ENST00000895533, ENST00000895534, ENST00000895535, ENST00000895536, ENST00000895537, ENST00000895538, ENST00000895539, ENST00000895540, ENST00000895541, ENST00000895542, ENST00000895543, ENST00000895544, ENST00000895545, ENST00000895546, ENST00000895547, ENST00000895548, ENST00000895549, ENST00000895550, ENST00000895551, ENST00000895552, ENST00000895553, ENST00000895554, ENST00000895555, ENST00000895556, ENST00000895557, ENST00000895558, ENST00000895559, ENST00000895560, ENST00000895561, ENST00000895562, ENST00000895563, ENST00000895564, ENST00000895565, ENST00000895566, ENST00000895567, ENST00000895568, ENST00000895569, ENST00000895570, ENST00000895571, ENST00000895572, ENST00000895573, ENST00000895574, ENST00000895575, ENST00000895576, ENST00000895577, ENST00000895578, ENST00000895579, ENST00000895580, ENST00000895581, ENST00000895582, ENST00000895583, ENST00000895584, ENST00000895585, ENST00000895586, ENST00000895587, ENST00000895588, ENST00000895589, ENST00000895590, ENST00000895591, ENST00000895592, ENST00000895593, ENST00000895594, ENST00000895595, ENST00000895596, ENST00000895597, ENST00000895598, ENST00000964030, ENST00000964031, ENST00000964032, ENST00000964033, ENST00000964034, ENST00000964035, ENST00000964036, ENST00000964037, ENST00000964038, ENST00000964039, ENST00000964040, ENST00000964041, ENST00000964042, ENST00000964043, ENST00000964044, ENST00000964045, ENST00000964046, ENST00000964047, ENST00000964048, ENST00000964049, ENST00000964050, ENST00000964051, ENST00000964052, ENST00000964053, ENST00000964054, ENST00000964055, ENST00000964056, ENST00000964057, ENST00000964058, ENST00000964059, ENST00000964060, ENST00000964061, ENST00000964062, ENST00000964063, ENST00000964064, ENST00000964065, ENST00000964066, ENST00000964067, ENST00000964068, ENST00000964069, ENST00000964070, ENST00000964071, ENST00000964072, ENST00000964073, ENST00000964074, ENST00000964075, ENST00000964076, ENST00000964077, ENST00000964078, ENST00000964079, ENST00000964080, ENST00000964081, ENST00000964082, ENST00000964083, ENST00000964084, ENST00000964085, ENST00000964086, ENST00000964087, ENST00000964088, ENST00000964089, ENST00000964090, ENST00000964091, ENST00000964092, ENST00000964093, ENST00000964094, ENST00000964095, ENST00000964096, ENST00000964097, ENST00000964098, ENST00000964099, ENST00000964100, ENST00000964101, ENST00000964102, ENST00000964103, ENST00000964104, ENST00000964105, ENST00000964106, ENST00000964107, ENST00000964108, ENST00000964109, ENST00000964110, ENST00000964111, ENST00000964112, ENST00000964113, ENST00000964114, ENST00000964115, ENST00000964116, ENST00000964117, ENST00000964118, ENST00000964119, ENST00000964120, ENST00000964121, ENST00000964122, ENST00000964123, ENST00000964124, ENST00000964125, ENST00000964126, ENST00000964127, ENST00000964128, ENST00000964129, ENST00000964130, ENST00000964131

RefSeq mRNA: 6 — MANE Select: NM_005411 NM_001093770, NM_001164644, NM_001164645, NM_001164646, NM_001164647, NM_005411

CCDS: CCDS44444, CCDS44445

Canonical transcript exons

ENST00000398636 — 6 exons

Exon	Start	End
ENSE00002226403	79611319	79611389
ENSE00002316011	79610939	79610982
ENSE00002438638	79613189	79613266
ENSE00003474795	79612312	79612431
ENSE00003492475	79611803	79611997
ENSE00003897398	79613737	79615443

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 97.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8112 / max 1247.7230, expressed in 13 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105810	1.7507	13
105809	0.0492	7
105808	0.0112	6

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	97.94	gold quality
upper lobe of left lung	UBERON:0008952	97.91	gold quality
lung	UBERON:0002048	95.78	gold quality
apex of heart	UBERON:0002098	78.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.08	gold quality
islet of Langerhans	UBERON:0000006	72.41	gold quality
vastus lateralis	UBERON:0001379	64.98	gold quality
gastrocnemius	UBERON:0001388	58.91	gold quality
heart left ventricle	UBERON:0002084	58.85	gold quality
pancreas	UBERON:0001264	58.78	gold quality
right lobe of thyroid gland	UBERON:0001119	58.06	gold quality
vermiform appendix	UBERON:0001154	56.58	gold quality
sural nerve	UBERON:0015488	56.06	gold quality
colonic epithelium	UBERON:0000397	55.07	gold quality
right atrium auricular region	UBERON:0006631	54.76	gold quality
left lobe of thyroid gland	UBERON:0001120	54.58	gold quality
cerebellar hemisphere	UBERON:0002245	54.48	gold quality
muscle of leg	UBERON:0001383	54.30	gold quality
mucosa of stomach	UBERON:0001199	53.99	gold quality
cerebellar cortex	UBERON:0002129	53.94	gold quality
cerebellum	UBERON:0002037	53.77	gold quality
popliteal artery	UBERON:0002250	53.56	gold quality
tibial artery	UBERON:0007610	53.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.08	gold quality
heart	UBERON:0000948	53.07	gold quality
amygdala	UBERON:0001876	52.97	gold quality
blood	UBERON:0000178	52.92	gold quality
right frontal lobe	UBERON:0002810	52.64	gold quality
temporal lobe	UBERON:0001871	52.62	gold quality
left adrenal gland cortex	UBERON:0035825	52.53	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	25937.85
E-GEOD-130148	yes	21827.95
E-MTAB-6653	yes	15441.33
E-HCAD-1	yes	15087.50
E-MTAB-6308	yes	9569.96
E-GEOD-86618	yes	6407.35
E-MTAB-8530	yes	4407.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPD, ESRRA, FOS, MYB, MYBL2, NCOA2, NFKB1, NKX2-1, NR3C1, RELA, USF1

miRNA regulators (miRDB)

50 targeting SFTPA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-11399	98.71	65.69	869

Literature-anchored findings (GeneRIF, showing 40)

• By binding C1q and preventing it from activating complement, and by blocking C1 complex formation, SP-A protects the delicate alveolar epithelium from inflammation and damage. (PMID:11714829)
• We propose that SP-A modulates inflammatory responses against the bacterial components by interactions with pattern-recognition receptors. (PMID:11724772)
• Potential role of nuclear factor kappaB and reactive oxygen species in cAMP and cytokine regulation of surfactant protein-A gene expression in lung type II cells (PMID:12040027)
• Human SP-A induces the secretion of immunoregulatory molecules such as TNF-alpha and IL-10 by two well-defined populations of human and murine macrophages. (PMID:12055204)
• SP-A selectively enhances mannose receptor expression on monocyte-derived macrophages, a process involving both the attached sugars and collagen-like domain of SP-A. (PMID:12244146)
• SP-A enhances phagocytosis of apoptotic cells by human and murine alveolar macrophages in vitro, independent of the apoptotic cell type. (PMID:12244199)
• Inhibition of T cell proliferation by SP-A occurs via an IL-2-dependent mechanism observed with accessory cell-dependent T cell mitogens and specific antigen, and IL-2-independent mechanism that potentially involves attenuation of cytosolic free calcium. (PMID:12421966)
• structural analysis and lipid-binding properties of recombinant human protein derived from one or both genes (PMID:12437362)
• intronic polymorphism of SP-A1 (C1416T) and redundant polymorphism of SP-A2 (A redundant SNPA1660G)showed significant association with pulmonary tuberculosis (PMID:12476938)
• SP-A2 binds with a higher affinity to a wider variety of sugars than SP-A1 at either 1 or 5 mM Ca(2+). (PMID:12505869)
• This protein decreases nitric oxide production by macrophages in a tumor necrosis factor-alpha-dependent mechanism. (PMID:12654642)
• Pseudomonas aeruginosa elastase degrades this protein in human lung. (PMID:12654643)
• SP-A and SP-D are antimicrobial proteins that directly inhibit the proliferation of Gram-negative bacteria in a macrophage- and aggregation-independent manner by increasing the permeability of the microbial cell membrane (PMID:12750409)
• SP-A enhances apoptotic neutrophil(PNM) uptake, stimulates alveolar macrophage(AM) TGF-beta1 release, and modulates the amount of TGF-beta1 released when AMs phagocytose apoptotic PMNs. (PMID:12794007)
• SP-A significantly attenuates zymosan-induced TNF-alpha secretion in murine RAW264.7 cells and alveolar macrophages in a concentration-dependent manner, and can down-regulate TLR2-mediated signaling and TNF-alpha secretion stimulated by zymosan. (PMID:12817025)
• SP-A induced expression of MMP-9 in both cell types, effect was time and dose dependent, and MMP-9 was released in its zymogen form. May influence protease/antiprotease balance in lungs with changes in surfactant constituents. (PMID:12842807)
• Expression of SP-A was used to characterize the fibroblast cells dedrived from synovial membrane. (PMID:12846554)
• variants may serve as markers to identify subgroups of patients at risk, and may contribute to pulmonary fibrosis (PMID:13680361)
• Data show that surfactant proteins-A and -D bind SIRPalpha through globular heads to block proinflammatory mediator production, while binding to their collagenous tails stimulates proinflammatory mediator production through binding to calreticulin. (PMID:14531999)
• differences among SP-A variants may partly explain the individual variability of pulmonary complications observed during bleomycin chemotherapy and/or in an environment that may promote protein oxidation. (PMID:14617519)
• Glucocorticoid receptor inhibits SP-A promoter activity through the ttf-1 binding element. (PMID:14633512)
• Examination of different immunohistochemical marker SP-A is helpful in the diagnosis and differential diagnosis of pulmonary sclerosing hemangioma. (PMID:14720435)
• tetradecanoylphorbol acetate inhibits SP-A gene expression via novel isoforms of PKC, the p44/42 MAPK pathway, and the activator protein-1 complex. (PMID:14751851)
• effect of lipid peroxidation (LPO) on the function of surfactant protein A (SP-A) (PMID:15026426)
• SP-A interacts with chlamydial pathogens and enhance their phagocytosis into macrophages (PMID:15075250)
• surfactant proteins A and D and mannose-binding lectin play roles in inflammation caused by DNA in lungs and other tissues (PMID:15145932)
• Lung adenocarcinoma tissues display higher SP-A1/SP-A2 than the corresponding tumor-free tissues and that the variation of SP-A-mRNA expression rises in cases of higher tumor-grading. (PMID:15216431)
• Data describe a proteome analysis of surfactant proteins SP-A and SP-D in bronchoalveolar lavage fluid from patients with cystic fibrosis, chronic bronchitis and pulmonary alveolar proteinosis. (PMID:15274124)
• anti-inflammatory effects of SP-A on LPS-challenged alveolar macrophages are associated with a SP-A-mediated direct modulation of the IkappaB-alpha turnover (PMID:15308505)
• Human SP-A variants in vitro enhance association of P. aeruginosa with rat alveolar macrophages differentially and in a concentration-dependent manner, with SP-A2 variants having a higher activity compared with SP-A1 variants. (PMID:15377498)
• SP-D, SP-A, and gp340 showed cooperative antiviral interactions (PMID:15608147)
• a supratrimeric assembly is not essential for the binding of surfactant protein A to ligands and anti-inflammatory effects of SP-A (PMID:15615713)
• Genetic polymorphism in surfactant protein A is associated with the development of chronic obstructive pulmonary disease in the Chinese Hans. (PMID:15696492)
• binds to Mycoplasma pneumoniae surface protein MPN372 (PMID:15845487)
• SP-A is a major microbial permeablizing factor in lavage fluid and that oxidative stress inhibits the antibacterial activity of SP-A by a mechanism that includes oxidative modification and functional inactivation of the protein (PMID:15890661)
• hSP-A1 5’-UTR splice variants play an important role in both SP-A translation and mRNA stability. (PMID:15894557)
• studies suggest that SP-A could contribute to modulate Re-LPS responses by altering the competence of the LBP-CD14 receptor complex (PMID:15932345)
• Deletions of the SP-A gene are specific genomic aberrations in bronchial epithelial cells adjacent to and within NSCLC, and are associated with tumor progression and a history of smoking (PMID:16061856)
• SP-A produced in the lung plays a role in modulating macrophage biology, thereby contributing to the alternative activation state of the alveolar macrophage. (PMID:16081790)
• role in Aspergillus mediated allergies and infections (PMID:16114131)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sftpa1	ENSMUSG00000021789
rattus_norvegicus	Sftpa1	ENSRNOG00000011438

Paralogs (4): COLEC11 (ENSG00000118004), SFTPD (ENSG00000133661), COLEC10 (ENSG00000184374), SFTPA2 (ENSG00000185303)

Protein

Protein identifiers

Pulmonary surfactant-associated protein A1 — Q8IWL2 (reviewed: Q8IWL2)

Alternative names: 35 kDa pulmonary surfactant-associated protein, Alveolar proteinosis protein, Collectin-4

All UniProt accessions (2): A0A0C4DG36, Q8IWL2

UniProt curated annotations — full annotation on UniProt →

Function. In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration. Enhances the expression of MYO18A/SP-R210 on alveolar macrophages. (Microbial infection) Recognition of M.tuberculosis by dendritic cells may occur partially via this molecule. Can recognize, bind, and opsonize pathogens to enhance their elimination by alveolar macrophages. (Microbial infection) Binds M.pneumoniae CARDS toxin, serves as one receptor for this pathogen. When SFTPA1 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen.

Subunit / interactions. Oligomeric complex of 6 set of homotrimers. Interacts with CD93. (Microbial infection) Binds M.bovis cell surface protein Apa via its glycosylated sites; probably also recognizes other bacterial moieties. (Microbial infection) Binds to the S.aureus extracellular adherence protein, Eap, thereby enhancing phagocytosis and killing of S.aureus by alveolar macrophages. (Microbial infection) Interacts with M.pneumoniae CARDS toxin; CARDS probably uses this protein as a receptor.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Surface film.

Post-translational modifications. N-acetylated.

Disease relevance. Interstitial lung disease 1 (ILD1) [MIM:619611] A form of interstitial lung disease, a heterogeneous group of diseases affecting the distal part of the lung and characterized by a progressive remodeling of the alveolar interstitium. The disease spectrum ranges from idiopathic interstitial pneumonia or pneumonitis to idiopathic pulmonary fibrosis, that is associated with an increased risk of developing lung cancer. Clinical features of interstitial lung disease include dyspnea, clubbing of the fingers, and restrictive lung capacity. ILD1 inheritance can be autosomal dominant with incomplete penetrance, and autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Respiratory distress syndrome in premature infants (RDS) [MIM:267450] A lung disease affecting usually premature newborn infants. It is characterized by deficient gas exchange, diffuse atelectasis, high-permeability lung edema and fibrin-rich alveolar deposits called ‘hyaline membranes’. Disease susceptibility may be associated with variants affecting the gene represented in this entry. The association between SFTPA1 alleles and respiratory distress syndrome in premature infants is dependent on a variation Ile to Thr at position 131 in SFTPB.

Polymorphism. At least 5 allelic variants of SFTPA1 are known: 6A, 6A(2), 6A(3), 6A(4) and 6A(5). The sequence shown is that of allele 6A(3).

Miscellaneous. Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).

Similarity. Belongs to the SFTPA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWL2-1	1	yes
Q8IWL2-2	2

RefSeq proteins (6): NP_001087239, NP_001158116, NP_001158117, NP_001158118, NP_001158119, NP_005402* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033990	Collectin_CTLD	Domain
IPR051663	CLec_Tetranectin-domain	Family

Pfam: PF00059

UniProt features (34 total): sequence variant 10, modified residue 9, disulfide bond 3, sequence conflict 3, domain 2, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWL2-F1	83.15	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 42, 54, 57, 63, 67, 70, 30, 33, 36

Disulfide bonds (3): 26, 155–246, 224–238

Glycosylation sites (1): 207

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-391160	Signal regulatory protein family interactions
R-HSA-5683826	Surfactant metabolism
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-5688849	Defective CSF2RB causes SMDP5
R-HSA-5688890	Defective CSF2RA causes SMDP4
R-HSA-1500931	Cell-Cell communication
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-392499	Metabolism of proteins
R-HSA-5668914	Diseases of metabolism
R-HSA-5687613	Diseases associated with surfactant metabolism

MSigDB gene sets: 138 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOCC_COLLAGEN_TRIMER, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, MODULE_410, GOBP_IMMUNE_EFFECTOR_PROCESS, GOBP_IMPORT_INTO_CELL, GOBP_LIPID_LOCALIZATION, GOBP_ENDOCYTOSIS, GOBP_PHAGOCYTOSIS, GOBP_PHAGOCYTOSIS_RECOGNITION, GOCC_CLATHRIN_COATED_VESICLE, GOCC_MULTIVESICULAR_BODY

GO Biological Process (3): respiratory gaseous exchange by respiratory system (GO:0007585), opsonization (GO:0008228), lipid transport (GO:0006869)

GO Molecular Function (3): lipid carrier activity (GO:0005319), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), multivesicular body (GO:0005771), endoplasmic reticulum membrane (GO:0005789), lamellar body (GO:0042599), clathrin-coated endocytic vesicle (GO:0045334)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Toll-like Receptor Cascades	3
Diseases associated with surfactant metabolism	2
Toll Like Receptor 2 (TLR2) Cascade	1
Cell-Cell communication	1
Metabolism of proteins	1
Immune System	1
Innate Immune System	1
Disease	1
Diseases of metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
multicellular organismal process	1
immune effector process	1
phagocytosis, recognition	1
transport	1
lipid localization	1
molecular carrier activity	1
cellular anatomical structure	1
protein-containing complex	1
late endosome	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
secretory granule	1
clathrin-coated vesicle	1
endocytic vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SFTPA1	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.560
cards	SFTPA1	psi-mi:“MI:0915”(physical association)	0.540
cards	SFTPA1	psi-mi:“MI:0407”(direct interaction)	0.540

BioGRID (7): SFTPA1 (Reconstituted Complex), SFTPA1 (Reconstituted Complex), PRDX6 (Reconstituted Complex), SFTPD (Co-purification), DMBT1 (Co-purification), DMBT1 (Reconstituted Complex), SFTPA1 (Reconstituted Complex)

ESM2 similar proteins: B1A4N2, B1A4P2, B1A4P8, B1A4Q3, B1A4Q5, C0STK6, O02659, P06908, P08427, P08661, P11226, P12842, P19999, P23805, P35242, P35247, P35248, P39039, P41317, P42916, P49874, P50403, P50404, Q1PBC5, Q2LK95, Q5M8X6, Q5U9S1, Q66S37, Q66S41, Q66S45, Q66S50, Q66S54, Q66S58, Q66S60, Q66S61, Q66S62, Q66S63, Q66S64, Q66S65, Q6RXL1

Diamond homologs: A1XRN2, B1A4M7, B1A4N2, B1A4N8, B1A4P2, B1A4P6, B1A4P7, B1A4P8, B1A4P9, B1A4Q0, B1A4Q2, B1A4Q3, B1A4Q5, B1A4Q6, B1A4Q8, B1A4Q9, B1A4R0, B1A4R4, B2D1Y0, C0STK6, P06908, P08427, P0DQP8, P12842, P21755, P21756, P35242, P35246, P49874, P50404, P81077, P82142, Q66S45, Q6RXL1, Q8AXS4, Q8AYA2, Q8IWL1, Q8IWL2, Q95L88, Q9N1X4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

107 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	53
Likely benign	20
Benign	21

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1322016	NM_005411.5(SFTPA1):c.631T>C (p.Trp211Arg)	Pathogenic
1322018	NM_005411.5(SFTPA1):c.673G>A (p.Val225Met)	Pathogenic
1325403	NM_005411.5(SFTPA1):c.532G>A (p.Val178Met)	Pathogenic
1325404	NM_005411.5(SFTPA1):c.622T>C (p.Tyr208His)	Pathogenic

SpliceAI

1003 predictions. Top by Δscore:

Variant	Effect	Δscore
10:79612308:GCAG:G	acceptor_loss	1.0000
10:79612310:A:AG	acceptor_gain	1.0000
10:79612310:AG:A	acceptor_gain	1.0000
10:79612311:G:GA	acceptor_gain	1.0000
10:79612311:GG:G	acceptor_gain	1.0000
10:79612311:GGCC:G	acceptor_gain	1.0000
10:79612311:GGCCC:G	acceptor_gain	1.0000
10:79612428:CCAGG:C	donor_loss	1.0000
10:79612430:AGGTG:A	donor_loss	1.0000
10:79612431:GGTGA:G	donor_loss	1.0000
10:79612432:G:GA	donor_loss	1.0000
10:79611895:G:GT	donor_gain	0.9900
10:79612307:T:A	acceptor_gain	0.9900
10:79612311:GGC:G	acceptor_gain	0.9900
10:79612388:A:T	donor_gain	0.9900
10:79611954:C:T	donor_gain	0.9800
10:79611958:G:T	donor_gain	0.9800
10:79611993:TCCAG:T	donor_loss	0.9800
10:79611994:CCAGG:C	donor_loss	0.9800
10:79611995:CAGG:C	donor_loss	0.9800
10:79611996:AGGT:A	donor_loss	0.9800
10:79611997:GGT:G	donor_loss	0.9800
10:79611998:G:GA	donor_loss	0.9800
10:79611999:T:A	donor_loss	0.9800
10:79612432:G:GG	donor_gain	0.9800
10:79611908:G:GT	donor_gain	0.9700
10:79611972:TCTCA:T	donor_gain	0.9700
10:79613173:G:A	acceptor_gain	0.9700
10:79613735:A:AG	acceptor_gain	0.9700
10:79613736:G:GG	acceptor_gain	0.9700

AlphaMissense

1602 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:79614065:G:C	W233C	0.993
10:79614065:G:T	W233C	0.993
10:79614108:T:C	F248L	0.992
10:79614110:C:A	F248L	0.992
10:79614110:C:G	F248L	0.992
10:79614063:T:A	W233R	0.991
10:79614063:T:C	W233R	0.991
10:79613999:G:C	W211C	0.985
10:79613999:G:T	W211C	0.985
10:79614109:T:G	F248C	0.980
10:79614064:G:C	W233S	0.976
10:79613782:T:C	F139S	0.972
10:79614109:T:C	F248S	0.970
10:79614036:T:A	C224S	0.966
10:79614037:G:C	C224S	0.966
10:79613782:T:G	F139C	0.965
10:79613854:C:A	A163D	0.959
10:79614102:T:A	C246S	0.959
10:79614103:G:C	C246S	0.959
10:79613997:T:A	W211R	0.958
10:79613997:T:C	W211R	0.958
10:79614091:G:C	R242P	0.956
10:79613958:T:C	F198L	0.954
10:79613960:C:A	F198L	0.954
10:79613960:C:G	F198L	0.954
10:79613879:T:A	N171K	0.951
10:79613879:T:G	N171K	0.951
10:79614103:G:A	C246Y	0.948
10:79614064:G:T	W233L	0.947
10:79613808:T:C	F148L	0.946

dbSNP variants (sampled 300 via entrez): RS1000017533 (10:79614588 C>G), RS1000273415 (10:79612499 G>A,C), RS1000426450 (10:79609932 G>A,T), RS1000881265 (10:79613274 G>A,T), RS1001545985 (10:79615429 G>A), RS1001598451 (10:79615637 C>T), RS1001839447 (10:79614898 C>G,T), RS1001935366 (10:79614692 G>T), RS1001944516 (10:79611592 C>T), RS1002641659 (10:79609290 C>G), RS1003623699 (10:79610617 G>C), RS1004272089 (10:79609512 G>C), RS1004316246 (10:79610857 G>A), RS1004392703 (10:79613897 C>A,T), RS1004495654 (10:79614363 T>C)

Disease associations

OMIM: gene MIM:178630 | disease phenotypes: MIM:619611, MIM:611913, MIM:178500

GenCC curated gene-disease

Disease	Classification	Inheritance
interstitial lung disease 1	Strong	Semidominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
interstitial lung disease 1	Moderate	AD

Mondo (3): interstitial lung disease 1 (MONDO:0030608), proximal 16p11.2 microdeletion syndrome (MONDO:0012756), interstitial lung disease 2 (MONDO:0800497)

Orphanet (3): Proximal 16p11.2 microdeletion syndrome (Orphanet:261197), Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001063	Acrocyanosis
HP:0001217	Clubbing
HP:0002020	Gastroesophageal reflux
HP:0002091	Restrictive ventilatory defect
HP:0002094	Dyspnea
HP:0002110	Bronchiectasis
HP:0002206	Pulmonary fibrosis
HP:0002875	Exertional dyspnea
HP:0003546	Exercise intolerance
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0010444	Pulmonic regurgitation
HP:0011462	Young adult onset
HP:0012378	Fatigue
HP:0012735	Cough
HP:0025175	Honeycomb lung
HP:0025179	Ground-glass opacification
HP:0025390	Reticular pattern on pulmonary HRCT
HP:0030830	Crackles
HP:0030879	Interlobular septal thickening
HP:0031631	Subpleural honeycombing
HP:0031950	Usual interstitial pneumonia
HP:0032341	Reduced forced vital capacity
HP:0032977	Elevated bronchoalveolar lavage fluid neutrophil proportion
HP:0032987	Elevated bronchoalveolar lavage fluid eosinophil proportion
HP:0033367	Orthodeoxia
HP:0033584	Nonspecific interstitial pneumonia
HP:0033638	Intralobular septal thickening

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C579850	16p11.2 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Ozone	increases expression, increases reaction, increases oxidation, affects response to substance, increases abundance (+3 more)	4
Silicon Dioxide	decreases expression, decreases reaction, increases reaction, increases expression	2
Particulate Matter	affects localization, increases expression, affects expression	2
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, decreases reaction	1
calfactant	decreases reaction, increases expression, increases reaction, affects binding	1
pyrazolanthrone	decreases expression, decreases reaction	1
lipopolysaccharide, E. coli O26-B6	decreases reaction, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetylcysteine	decreases expression, decreases reaction	1
Adenosine Triphosphate	affects binding, decreases reaction, increases secretion	1
Air Pollutants	affects response to substance, increases abundance	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Bleomycin	increases reaction, decreases reaction, affects cotreatment, increases expression, affects binding	1
Calcitriol	decreases expression	1
Dexamethasone	decreases expression, decreases reaction	1
Lipopolysaccharides	increases expression	1
Nitrogen Oxides	affects response to substance, increases abundance	1
Paraquat	increases expression	1
Phosphatidylcholines	affects binding, decreases reaction, increases secretion	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases nitrosation	1
Thiram	decreases expression, decreases reaction	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

4 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04271332	PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, and Efficacy of Arbaclofen in 16p11.2 Deletion
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
NCT06372353	Not specified	COMPLETED	The Effect Of Baduanjin Exercises In Patients With Idiopathic Pulmonary Fibrosis
NCT06644144	Not specified	RECRUITING	P4O2 ILD Extension