SFTPA2

Summary

SFTPA2 (surfactant protein A2, HGNC:10799) is a protein-coding gene on chromosome 10q22.3, encoding Pulmonary surfactant-associated protein A2 (Q8IWL1). 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 is one of several genes encoding pulmonary-surfactant associated proteins (SFTPA) located on chromosome 10. Mutations in this gene and a highly similar gene located nearby, which affect the highly conserved carbohydrate recognition domain, are associated with idiopathic pulmonary fibrosis. The current version of the assembly displays only a single centromeric SFTPA gene pair rather than the two gene pairs shown in the previous assembly which were thought to have resulted from a duplication.

Source: NCBI Gene 729238 — RefSeq curated summary.

At a glance

• Gene–disease (curated): interstitial lung disease 2 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 108 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 27
• MANE Select transcript: NM_001098668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10799
Approved symbol	SFTPA2
Name	surfactant protein A2
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	SP-A2, COLEC5
Ensembl gene	ENSG00000185303
Ensembl biotype	protein_coding
OMIM	178642
Entrez	729238

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 62 protein_coding

ENST00000372325, ENST00000372327, ENST00000417041, ENST00000492049, ENST00000640627, ENST00000905085, ENST00000905086, ENST00000905087, ENST00000905088, ENST00000905089, ENST00000905090, ENST00000905091, ENST00000905092, ENST00000905093, ENST00000905094, ENST00000905095, ENST00000905096, ENST00000905097, ENST00000905098, ENST00000905099, ENST00000905100, ENST00000905101, ENST00000905102, ENST00000905103, ENST00000905104, ENST00000905105, ENST00000905106, ENST00000905107, ENST00000905108, ENST00000905109, ENST00000905110, ENST00000905111, ENST00000905112, ENST00000905113, ENST00000905114, ENST00000905115, ENST00000905116, ENST00000905117, ENST00000905118, ENST00000905119, ENST00000959070, ENST00000959071, ENST00000959072, ENST00000959073, ENST00000959074, ENST00000959075, ENST00000959076, ENST00000959077, ENST00000959078, ENST00000959079, ENST00000959080, ENST00000959081, ENST00000959082, ENST00000959083, ENST00000959084, ENST00000959085, ENST00000959086, ENST00000959087, ENST00000959088, ENST00000959089, ENST00000959090, ENST00000959091

RefSeq mRNA: 3 — MANE Select: NM_001098668 NM_001098668, NM_001320813, NM_001320814

CCDS: CCDS41540

Canonical transcript exons

ENST00000372325 — 6 exons

Exon	Start	End
ENSE00001725562	79559969	79559998
ENSE00001801423	79555852	79557585
ENSE00002441977	79559312	79559506
ENSE00002453165	79560364	79560407
ENSE00002465646	79558052	79558129
ENSE00002514143	79558886	79559005

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 100.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2633 / max 197.9495, expressed in 10 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110311	0.2149	9
110312	0.0484	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	100.00	gold quality
adult organism	UBERON:0007023	99.90	gold quality
visceral pleura	UBERON:0002401	99.71	gold quality
upper lobe of lung	UBERON:0008948	97.96	gold quality
right lung	UBERON:0002167	97.93	gold quality
upper lobe of left lung	UBERON:0008952	97.82	gold quality
lung	UBERON:0002048	95.99	gold quality
apex of heart	UBERON:0002098	77.59	gold quality
bronchial epithelial cell	CL:0002328	76.81	gold quality
bronchus	UBERON:0002185	73.00	gold quality
epithelium of bronchus	UBERON:0002031	72.86	gold quality
cerebellar hemisphere	UBERON:0002245	71.61	gold quality
cerebellar cortex	UBERON:0002129	71.28	gold quality
pleura	UBERON:0000977	71.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.55	gold quality
trachea	UBERON:0003126	70.54	gold quality
prostate gland	UBERON:0002367	70.51	gold quality
cerebellum	UBERON:0002037	69.77	gold quality
mucosa of sigmoid colon	UBERON:0004993	68.45	gold quality
colonic mucosa	UBERON:0000317	67.49	gold quality
tongue squamous epithelium	UBERON:0006919	65.79	gold quality
mucosa of transverse colon	UBERON:0004991	65.57	gold quality
vermiform appendix	UBERON:0001154	64.76	gold quality
rectum	UBERON:0001052	63.89	gold quality
right frontal lobe	UBERON:0002810	63.05	gold quality
anterior cingulate cortex	UBERON:0009835	61.45	gold quality
cingulate cortex	UBERON:0003027	61.40	gold quality
caecum	UBERON:0001153	60.95	gold quality
gastrocnemius	UBERON:0001388	60.90	gold quality
right lobe of thyroid gland	UBERON:0001119	60.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	27232.94
E-HCAD-15	yes	24160.48
E-HCAD-1	yes	16850.72
E-MTAB-6653	yes	15995.01
E-GEOD-86618	yes	15099.43
E-MTAB-6308	yes	10504.57
E-MTAB-8530	yes	2348.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, ESRRA, NKX2-1, TTF1

miRNA regulators (miRDB)

56 targeting SFTPA2, 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-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4306	99.72	70.50	3630
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-4276	99.56	67.66	2514
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6829-5P	98.86	65.12	1480

Literature-anchored findings (GeneRIF, showing 39)

• Decreased levels of SP-A and SP-D have been measured in bronchoalveolar lavage fluid of these patients, as well as patients with acute pneumonia but no chronic lung disease. (review) (PMID:16406431)
• We conclude that SP-A permeabilizes phospholipid membranes in an LPS-dependent and rough LPS-specific manner, that the effect is neither SP-A- nor species-specific, and that oxidative damage to SP-A abolishes its membrane destabilizing properties (PMID:16489761)
• Residue 85 plays an important role in the structure and function of SP-A and is a major factor for the differences between SP-A1 and SP-A2 variants. (PMID:17580966)
• TTF-1 response element is critical for temporal and spatial regulation and necessary for hormonal regulation of human surfactant protein-A2 promoter activity (PMID:18487360)
• The amniotic fluid concentration of SP-A decreases in spontaneous human parturition at term. (PMID:18828058)
• These data are consistent with SFTPA2 germline mutations that interfere with protein trafficking and cause familial IPF and lung cancer. (PMID:19100526)
• SP-A1 and SP-A2, in addition to their roles in surfactant-related functions, play an important role in the modulation of lung host defense. (PMID:19392648)
• SP-A2 polymorphisms are associated with the severity of respiratory syncytial virus infection in infants (PMID:19914637)
• Electron microscopy analysis revealed that hTG mice with a single SP-A1(6A(4)) or SP-A2(1A(3)) gene product lacked tubular myelin (TM), but hTG mice carrying both had TM. (PMID:20048345)
• The mechanism of pulmonary fibrosis does not involve an overt lack of secreted SP-A but instead involves an increase in endoplasmic reticulum stress of resident type II alveolar epithelial cells. (PMID:20466729)
• These results indicate that the gene polymorphism at the residue 223 in the carbohydrate recognition domain of SFTPA2 may be a genetic marker for the development of allergic rhinitis in the adult Chinese Han population. (PMID:20963503)
• there is an association of risk for severe acute respiratory syncytial infection in variant forms of the surfactant protein A2 allele (PMID:21601013)
• The untranslated exon B of human surfactant protein A2 mRNAs is an enhancer for transcription and translation. (PMID:21840962)
• Surfactant protein A associated with respiratory distress syndrome in Korean preterm infants: evidence of ethnic difference. (PMID:23038062)
• SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and formed aggregates (PMID:23056344)
• The aim of this report is to describe the genetic complexity of the SFTPA1 and SFTPA2 genes, as well as to review regulatory mechanisms that control SP-A expression in humans and other animal species.[review] (PMID:23069847)
• findings show rs1650232 is in partial linkage disequilibrium with known SP-A2 marker single-nucleotide polymorphisms previously associated with risk for respiratory diseases including tuberculosis (PMID:23328842)
• proteins including the 14-3-3 family bind two cis-elements within exon B of hSP-A2 mRNA in a sequence- and secondary structure-specific manner. (PMID:23525782)
• sequence variability at the 3’UTR of SFTPA1 and SFTPA2 gene variants differentially affects miRNA regulation of gene expression. (PMID:24793167)
• data suggest an effect of genetic variants of SFTPA2 on the severity of pandemic H1N1 infection (PMID:24950659)
• This study shows that changes occur in the alveolar macrophage proteome in response to a single in vivo treatment with exogenous SP-A1 and/or SP-A2. (PMID:24954098)
• In this review, we highlight the associations of eosinophilic lung diseases with SP-A and SP-D levels and functions. (PMID:24960334)
• In this study, the loci and haplotypes associated with pulmonary tuberculosis (PTB) were found mostly to be located in the SFTPA2 gene, suggesting that the effects of the SFTPA2 gene on PTB are stronger than those of SFTPA1. (PMID:24984162)
• Expression of SFTPA2 mRNA and total SP-A protein was significantly lower in cancer tissue. (PMID:25514367)
• Genetic variation in SP-A2 leads to differential binding to Mycoplasma pneumoniae membranes and regulation of host responses. (PMID:25957169)
• Investigated the relationship between SP-A2 and SP-B gene polymorphisms and respiratory distress syndrome in preterm neonates. (PMID:26061924)
• In a Dutch cohort study of unrelated patients with idiopathic or familial interstitial pneumonia genetic analysis of SFTPA2 three new mutations in exon 6 of SFTPA2: N210T, G231R, and N171Y were identified. None were found in the control group. (PMID:26568241)
• Significant differences in frequency of occurrence of unfavorable genotypes CC rs1965708, AA rs1059046 of SFTPA2 gene and CC rs1130866 of SFTPB gene in influenza patients in comparison with individuals of the control group were not detected. (PMID:26950992)
• SP-A1 6A4 and SP-A2 1A5 genetic variants may influence the susceptibility to respiratory distress syndrome in late-preterm infants, independently of the effect of other perinatal factors. (PMID:27835691)
• Donor surfactant protein A2 polymorphism and lung transplant survival. (PMID:31831583)
• Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer. (PMID:32587780)
• Identification and functional characterization of a novel surfactant protein A2 mutation (p.N207Y) in a Chinese family with idiopathic pulmonary fibrosis. (PMID:32602668)
• Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer. (PMID:32855221)
• Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice. (PMID:33141765)
• Identification of a Missense Mutation in the Surfactant Protein A2 Gene in a Chinese Family with Interstitial Lung Disease. (PMID:33181027)
• Human Surfactant Protein SP-A1 and SP-A2 Variants Differentially Affect the Alveolar Microenvironment, Surfactant Structure, Regulation and Function of the Alveolar Macrophage, and Animal and Human Survival Under Various Conditions. (PMID:34484180)
• Differential Regulation of Human Surfactant Protein A Genes, SFTPA1 and SFTPA2, and Their Corresponding Variants. (PMID:34917085)
• Small Peptide Derivatives Within the Carbohydrate Recognition Domain of SP-A2 Modulate Asthma Outcomes in Mouse Models and Human Cells. (PMID:35874703)
• Association of surfactant protein A2 with acute respiratory failure in children. (PMID:37888536)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sftpa1	ENSMUSG00000021789
rattus_norvegicus	Sftpa1	ENSRNOG00000011438

Paralogs (4): COLEC11 (ENSG00000118004), SFTPA1 (ENSG00000122852), SFTPD (ENSG00000133661), COLEC10 (ENSG00000184374)

Protein

Protein identifiers

Pulmonary surfactant-associated protein A2 — Q8IWL1 (reviewed: Q8IWL1)

Alternative names: 35 kDa pulmonary surfactant-associated protein, Alveolar proteinosis protein, Collectin-5

All UniProt accessions (4): Q8IWL1, A0A1W2PR89, R4GMN3, X6REF7

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.

Subunit / interactions. Oligomeric complex of 6 set of homotrimers.

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

Post-translational modifications. N-acetylated.

Disease relevance. Interstitial lung disease 2 (ILD2) [MIM:178500] 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. ILD2 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. At least 6 alleles of SFTPA2 are known: 1A, 1A(0), 1A(1), 1A(2), 1A(3) and 1A(4). The sequence shown is that of allele 1A(2).

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.

RefSeq proteins (3): NP_001092138, NP_001307742, NP_001307743 (=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 (38 total): sequence variant 15, modified residue 9, compositionally biased region 4, disulfide bond 3, domain 2, signal peptide 1, chain 1, glycosylation site 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWL1-F1	84.09	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): 33, 36, 42, 54, 57, 63, 67, 70, 30

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

Glycosylation sites (1): 207

Function

Pathways and Gene Ontology

Reactome pathways

17 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-5687868	Defective SFTPA2 causes IPF
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: 126 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOCC_COLLAGEN_TRIMER, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOCC_COATED_VESICLE, NAKAMURA_LUNG_CANCER_DIFFERENTIATION_MARKERS, GOCC_CLATHRIN_COATED_VESICLE, GOCC_MULTIVESICULAR_BODY, GOCC_SECRETORY_VESICLE, GOCC_ENDOCYTIC_VESICLE, GOCC_CLATHRIN_COATED_ENDOCYTIC_VESICLE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_LAMELLAR_BODY

GO Biological Process (1): respiratory gaseous exchange by respiratory system (GO:0007585)

GO Molecular Function (2): 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	3
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
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

14 interactions, top by confidence:

A	B	Type	Score
NCS1	SFTPA2	psi-mi:“MI:0915”(physical association)	0.560
SFTPA2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
SFTPA2	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
SFTPA2	POTEF	psi-mi:“MI:0914”(association)	0.350
SFTPA2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
UBQLN2	SFTPA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): CORO1B (Co-fractionation), CORO1C (Co-fractionation), SFTPA2 (Two-hybrid), UBQLN2 (Two-hybrid), SFTPA2 (Proximity Label-MS), HINT1 (Affinity Capture-MS), VHL (Affinity Capture-MS), RPTOR (Affinity Capture-MS), NXPH4 (Affinity Capture-MS), P3H1 (Affinity Capture-MS), PRPSAP2 (Affinity Capture-MS), LEPREL2 (Affinity Capture-MS), MTG2 (Affinity Capture-MS), LIMK2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	47
Likely benign	22
Benign	27

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
13200	NM_001098668.4(SFTPA2):c.593T>C (p.Phe198Ser)	Pathogenic
1322020	NM_001098668.4(SFTPA2):c.512A>T (p.Asn171Ile)	Pathogenic
1325405	NM_001098668.4(SFTPA2):c.697T>A (p.Trp233Arg)	Pathogenic
1705914	NM_001098668.4(SFTPA2):c.557A>G (p.Tyr186Cys)	Likely pathogenic
3027274	NM_001098668.4(SFTPA2):c.719_721del (p.Tyr240del)	Likely pathogenic

SpliceAI

896 predictions. Top by Δscore:

Variant	Effect	Δscore
10:79558881:CTCA:C	donor_loss	1.0000
10:79558882:TCA:T	donor_loss	1.0000
10:79558883:CACCT:C	donor_loss	1.0000
10:79558884:A:C	donor_loss	1.0000
10:79558885:C:CG	donor_loss	1.0000
10:79559001:GGGGC:G	acceptor_gain	1.0000
10:79559002:GGGC:G	acceptor_gain	1.0000
10:79559003:GGC:G	acceptor_gain	1.0000
10:79559004:GC:G	acceptor_gain	1.0000
10:79559004:GCCT:G	acceptor_loss	1.0000
10:79559005:CC:C	acceptor_gain	1.0000
10:79559006:C:CC	acceptor_gain	1.0000
10:79558145:C:CT	acceptor_gain	0.9900
10:79558145:C:T	acceptor_gain	0.9900
10:79558884:A:AC	donor_gain	0.9900
10:79558885:C:CC	donor_gain	0.9900
10:79559009:C:CT	acceptor_gain	0.9900
10:79559010:A:T	acceptor_gain	0.9900
10:79557586:C:CC	acceptor_gain	0.9800
10:79558050:ACCTC:A	donor_gain	0.9800
10:79558051:CCTCC:C	donor_gain	0.9800
10:79558054:C:A	donor_gain	0.9800
10:79558055:C:A	donor_gain	0.9800
10:79558128:CC:C	acceptor_gain	0.9800
10:79558129:CC:C	acceptor_gain	0.9800
10:79558130:C:A	acceptor_loss	0.9800
10:79559006:C:T	acceptor_gain	0.9800
10:79557583:GGGCT:G	acceptor_gain	0.9700
10:79557584:GGCTG:G	acceptor_gain	0.9700
10:79557587:T:C	acceptor_loss	0.9700

AlphaMissense

1595 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:79557257:C:A	W233C	0.995
10:79557257:C:G	W233C	0.995
10:79557212:G:C	F248L	0.992
10:79557212:G:T	F248L	0.992
10:79557214:A:G	F248L	0.992
10:79557259:A:G	W233R	0.992
10:79557259:A:T	W233R	0.992
10:79557323:C:A	W211C	0.986
10:79557323:C:G	W211C	0.986
10:79557213:A:C	F248C	0.984
10:79557258:C:G	W233S	0.981
10:79557219:C:G	C246S	0.980
10:79557220:A:T	C246S	0.980
10:79557540:A:G	F139S	0.977
10:79557285:C:G	C224S	0.976
10:79557286:A:T	C224S	0.976
10:79557468:G:T	A163D	0.975
10:79557213:A:G	F248S	0.973
10:79557540:A:C	F139C	0.972
10:79557219:C:T	C246Y	0.965
10:79557492:C:G	C155S	0.965
10:79557493:A:T	C155S	0.965
10:79557362:G:C	F198L	0.964
10:79557362:G:T	F198L	0.964
10:79557364:A:G	F198L	0.964
10:79557491:A:C	C155W	0.961
10:79557325:A:G	W211R	0.960
10:79557325:A:T	W211R	0.960
10:79557492:C:T	C155Y	0.959
10:79557220:A:G	C246R	0.958

dbSNP variants (sampled 300 via entrez): RS1000021680 (10:79560329 G>A), RS1000032208 (10:79559911 A>T), RS1000087773 (10:79555859 A>G), RS1000532194 (10:79557701 G>T), RS1001074161 (10:79561393 GC>G), RS1002193524 (10:79557118 G>A), RS1002376302 (10:79560697 G>T), RS1002385263 (10:79556886 C>G,T), RS1003354521 (10:79558637 C>T), RS1003372798 (10:79561589 G>A), RS1003791918 (10:79561768 A>G,T), RS1003930354 (10:79555555 A>G), RS1004064658 (10:79559399 T>C), RS1004388810 (10:79555771 A>G), RS1005590970 (10:79561975 T>C)

Disease associations

OMIM: gene MIM:178642 | disease phenotypes: MIM:178500, MIM:301022

GenCC curated gene-disease

Disease	Classification	Inheritance
interstitial lung disease 2	Strong	Autosomal dominant
idiopathic pulmonary fibrosis	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
interstitial lung disease 2	Definitive	AD

Mondo (5): interstitial lung disease 2 (MONDO:0800497), pulmonary fibrosis (MONDO:0002771), Mullegama-Klein-Martinez syndrome (MONDO:0026722), (MONDO:0800029), (MONDO:0008345)

Orphanet (2): Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001063	Acrocyanosis
HP:0001394	Cirrhosis
HP:0002020	Gastroesophageal reflux
HP:0002092	Pulmonary arterial hypertension
HP:0002094	Dyspnea
HP:0002110	Bronchiectasis
HP:0002206	Pulmonary fibrosis
HP:0002875	Exertional dyspnea
HP:0003546	Exercise intolerance
HP:0006519	Alveolar cell carcinoma
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0010444	Pulmonic regurgitation
HP:0010702	Increased circulating immunoglobulin concentration
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:0031631	Subpleural honeycombing
HP:0031950	Usual interstitial pneumonia
HP:0032341	Reduced forced vital capacity
HP:0032977	Elevated bronchoalveolar lavage fluid neutrophil proportion
HP:0033367	Orthodeoxia
HP:0045051	Decreased DLCO
HP:0100759	Clubbing of fingers

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011658	Pulmonary Fibrosis	C08.381.483.652; C23.550.355.644

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Ozone	decreases reaction, increases secretion, increases reaction, increases oxidation, affects cotreatment (+3 more)	3
Resveratrol	decreases expression, affects cotreatment	2
beta-lapachone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
calfactant	affects binding, decreases reaction, increases expression, increases reaction	1
abrine	increases expression	1
Adenosine Triphosphate	affects binding, decreases reaction, increases secretion	1
Atrazine	increases expression	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	increases methylation	1
Bleomycin	decreases reaction, affects cotreatment, increases expression, affects binding, increases reaction	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Phosphatidylcholines	affects binding, decreases reaction, increases secretion	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT07570888	PHASE4	NOT_YET_RECRUITING	This is a Trial Designed to Evaluate the Combination of Nerandomilast With Mycophenolate Across a Wide Variety of Pulmonary Fibrosis Subtypes, With the Aim of Providing Clinicians With Assurance That This is an Appropriate Therapeutic Combination.
NCT00004563	PHASE3	COMPLETED	Scleroderma Lung Disease
NCT00052039	PHASE3	TERMINATED	A Randomized, Double-Blind, Three-Arm, Phase 3b Study Comparing the Safety and Efficacy of Interferon Gamma-1b With Azathioprine, and Azathioprine Alone in Patients With IPF Receiving Prednisone
NCT00075998	PHASE3	TERMINATED	The INSPIRE Trial: A Study of Interferon Gamma-1b for Idiopathic Pulmonary Fibrosis (IPF)
NCT00076635	PHASE3	TERMINATED	An Open-Label Study of the Safety of Interferon Gamma-1b in Patients With IPF
NCT00517933	PHASE3	COMPLETED	Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
NCT00639496	PHASE3	COMPLETED	Study of the Effects of High-dose N-acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)
NCT00650091	PHASE3	COMPLETED	Evaluating the Effectiveness of Prednisone, Azathioprine, and N-acetylcysteine in Patients With IPF
NCT00896155	PHASE3	UNKNOWN	Trial of Concurrent Versus Sequential Tamoxifen With Radiotherapy in Breast Cancer Patients
NCT01335464	PHASE3	COMPLETED	Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients
NCT01335477	PHASE3	COMPLETED	Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT03267108	PHASE3	TERMINATED	A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT04979884	PHASE3	COMPLETED	Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT06025578	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis
NCT06238622	PHASE3	RECRUITING	A Follow-up Study to Test Long-term Treatment With Nerandomilast in People With Pulmonary Fibrosis Who Took Part in a Previous Study With Nerandomilast
NCT07201922	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis
NCT07441408	PHASE3	NOT_YET_RECRUITING	Long-term Extension Study to Evaluate Safety and Tolerability of Admilparant in Participants With Pulmonary Fibrosis
NCT07503587	PHASE3	NOT_YET_RECRUITING	Evaluating the Efficacy and Safety of of HSK44459 in People With Progressive Pulmonary Fibrosis
NCT00000596	PHASE2	COMPLETED	Diffuse Fibrotic Lung Disease
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT00052052	PHASE2	COMPLETED	An Open-Label Study of the Safety and Efficacy of Subcutaneous Recombinant Interferon-Gamma 1b (IFN-Gamma 1b) in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT00063869	PHASE2	COMPLETED	Study Evaluating the Safety and Efficacy of Etanercept in Patients With Idiopathic Pulmonary Fibrosis
NCT00080223	PHASE2	COMPLETED	Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis
NCT00109681	PHASE2	COMPLETED	Inhaled Iloprost in Adults With Abnormal Pulmonary Pressure and Associated With Idiopathic Pulmonary Fibrosis
NCT00352482	PHASE2	COMPLETED	Sildenafil to Increase Exercise Capacity in Individuals With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension
NCT00455767	PHASE2	COMPLETED	Safety and Efficacy Study of Depelestat in Acute Respiratory Distress Syndrome (ARDS) Patients
NCT00514683	PHASE2	COMPLETED	Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis
NCT00690885	PHASE2	TERMINATED	Interferon-alpha Treatment of Chronic Cough in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis
NCT00786201	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF)
NCT01135199	PHASE2	WITHDRAWN	Pomalidomide for Cough in Patients With Idiopathic Pulmonary Fibrosis
NCT01170065	PHASE2	COMPLETED	Roll Over Study From 1199.30 BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01203943	PHASE2	TERMINATED	A Study to Characterize the Safety, PK and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01417156	PHASE2	COMPLETED	Safety and PK Study of BIBF 1120 in Japanese Patients With IPF: Follow up Study From 1199.31(NCT01136174)
NCT01442779	PHASE2	COMPLETED	Clinical Trial of Low Dose Oral Interferon Alpha in Idiopathic Pulmonary Fibrosis
NCT01917877	PHASE2	UNKNOWN	Efficiency Study for Acute Radiation-induced and Chemotherapy-induced Pulmonary Fibrosis With Bevasizumab
NCT02603068	PHASE2	WITHDRAWN	Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis