SFTPB

Summary

SFTPB (surfactant protein B, HGNC:10801) is a protein-coding gene on chromosome 2p11.2, encoding Pulmonary surfactant-associated protein B (P07988). Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces.

This gene encodes the pulmonary-associated surfactant protein B (SPB), an amphipathic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. The SPB enhances the rate of spreading and increases the stability of surfactant monolayers in vitro. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 1, also called pulmonary alveolar proteinosis due to surfactant protein B deficiency, and are associated with fatal respiratory distress in the neonatal period. Alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 6439 — RefSeq curated summary.

At a glance

• Gene–disease (curated): surfactant metabolism dysfunction, pulmonary, 1 (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 256 total — 12 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 39
• MANE Select transcript: NM_000542

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10801
Approved symbol	SFTPB
Name	surfactant protein B
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SP-B
Ensembl gene	ENSG00000168878
Ensembl biotype	protein_coding
OMIM	178640
Entrez	6439

Gene structure

Transcript identifiers

Ensembl transcripts: 134 — 132 protein_coding, 2 retained_intron

ENST00000393822, ENST00000409383, ENST00000428225, ENST00000473692, ENST00000491167, ENST00000494165, ENST00000519937, ENST00000860670, ENST00000860671, ENST00000860672, ENST00000860673, ENST00000860674, ENST00000860675, ENST00000860676, ENST00000860677, ENST00000860678, ENST00000860679, ENST00000860680, ENST00000860681, ENST00000860682, ENST00000860683, ENST00000860684, ENST00000860685, ENST00000860686, ENST00000860687, ENST00000860688, ENST00000860689, ENST00000860690, ENST00000860691, ENST00000860692, ENST00000860693, ENST00000860694, ENST00000860695, ENST00000860696, ENST00000860697, ENST00000860698, ENST00000860699, ENST00000860700, ENST00000860701, ENST00000860702, ENST00000860703, ENST00000860704, ENST00000860705, ENST00000860706, ENST00000860707, ENST00000860708, ENST00000860709, ENST00000860710, ENST00000860711, ENST00000860712, ENST00000860713, ENST00000860714, ENST00000860715, ENST00000860716, ENST00000860717, ENST00000860718, ENST00000860719, ENST00000860720, ENST00000860721, ENST00000860722, ENST00000860723, ENST00000860724, ENST00000860725, ENST00000860726, ENST00000860727, ENST00000860728, ENST00000954879, ENST00000954880, ENST00000954881, ENST00000954882, ENST00000954883, ENST00000954884, ENST00000954885, ENST00000954886, ENST00000954887, ENST00000954888, ENST00000954889, ENST00000954890, ENST00000954891, ENST00000954892, ENST00000954893, ENST00000954894, ENST00000954895, ENST00000954896, ENST00000954897, ENST00000954898, ENST00000954899, ENST00000954900, ENST00000954901, ENST00000954902, ENST00000954903, ENST00000954904, ENST00000954905, ENST00000954906, ENST00000954907, ENST00000954908, ENST00000954909, ENST00000954910, ENST00000954911, ENST00000954912, ENST00000954913, ENST00000954914, ENST00000954915, ENST00000954916, ENST00000954917, ENST00000954918, ENST00000954919, ENST00000954920, ENST00000954921, ENST00000954922, ENST00000954923, ENST00000954924, ENST00000954925, ENST00000954926, ENST00000954927, ENST00000954928, ENST00000954929, ENST00000954930, ENST00000954931, ENST00000954932, ENST00000954933, ENST00000954934, ENST00000954935, ENST00000954936, ENST00000954937, ENST00000954938, ENST00000954939, ENST00000954940, ENST00000954941, ENST00000954942, ENST00000954943, ENST00000954944, ENST00000954945, ENST00000954946

RefSeq mRNA: 3 — MANE Select: NM_000542 NM_000542, NM_001367281, NM_198843

CCDS: CCDS1983

Canonical transcript exons

ENST00000519937 — 11 exons

Exon	Start	End
ENSE00001135249	85663346	85663491
ENSE00001135259	85663664	85663847
ENSE00001135266	85665289	85665378
ENSE00001135274	85665606	85665794
ENSE00001135279	85666617	85666742
ENSE00001154897	85661454	85661535
ENSE00001516582	85657314	85659682
ENSE00003460916	85667679	85667806
ENSE00003490775	85668117	85668199
ENSE00003497188	85667106	85667177
ENSE00003701547	85662029	85662109

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 36.7977 / max 27686.2256, expressed in 54 samples.

FANTOM5 promoters (45 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29498	34.2523	39
29486	0.6160	10
29463	0.2975	10
29487	0.2643	8
29471	0.1295	6
29481	0.1292	9
29484	0.1087	8
29477	0.0920	8
29489	0.0893	8
29453	0.0656	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.98	gold quality
visceral pleura	UBERON:0002401	99.95	gold quality
upper lobe of lung	UBERON:0008948	99.84	gold quality
upper lobe of left lung	UBERON:0008952	99.83	gold quality
right lung	UBERON:0002167	99.80	gold quality
adult organism	UBERON:0007023	99.09	gold quality
lung	UBERON:0002048	98.62	gold quality
tendon of biceps brachii	UBERON:0008188	94.86	gold quality
type B pancreatic cell	CL:0000169	94.50	silver quality
sperm	CL:0000019	94.17	gold quality
male germ cell	CL:0000015	94.15	silver quality
buccal mucosa cell	CL:0002336	93.93	gold quality
right lobe of thyroid gland	UBERON:0001119	93.79	gold quality
olfactory bulb	UBERON:0002264	93.11	silver quality
diaphragm	UBERON:0001103	90.89	silver quality
mucosa of paranasal sinus	UBERON:0005030	90.80	gold quality
left lobe of thyroid gland	UBERON:0001120	89.56	gold quality
epithelium of bronchus	UBERON:0002031	87.97	gold quality
thyroid gland	UBERON:0002046	87.89	gold quality
bronchial epithelial cell	CL:0002328	87.83	gold quality
bronchus	UBERON:0002185	87.81	gold quality
nasal cavity epithelium	UBERON:0005384	87.80	silver quality
cardia of stomach	UBERON:0001162	87.37	gold quality
cervix squamous epithelium	UBERON:0006922	87.25	silver quality
oocyte	CL:0000023	86.90	silver quality
ventral tegmental area	UBERON:0002691	85.49	silver quality
superficial temporal artery	UBERON:0001614	85.33	silver quality
cervix epithelium	UBERON:0004801	84.63	silver quality
epithelial cell of pancreas	CL:0000083	84.49	silver quality
subthalamic nucleus	UBERON:0001906	84.26	silver quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	37618.51
E-GEOD-130148	yes	25456.93
E-ANND-2	yes	21446.33
E-HCAD-1	yes	13617.89
E-CURD-126	yes	12862.04
E-MTAB-6653	yes	11820.24
E-MTAB-6308	yes	11776.71
E-CURD-122	yes	8909.70
E-MTAB-10662	yes	8425.63
E-GEOD-86618	yes	5453.14
E-MTAB-8221	yes	4230.47
E-MTAB-8530	yes	3282.53
E-HCAD-8	yes	2419.74
E-MTAB-9388	yes	10.49
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF2, CEBPB, CREB1, ESR2, FOXA1, FOXA2, FOXF2, FOXM1, IRF6, JUN, MYBBP1A, NCOA1, NCOA2, NCOA3, NF1, NKX2-1, PARP1, PAX3, PLAGL2, PPARG, RARA, RXRG, SMAD3, SP1, SP3, STAT3, STAT5A, TGFB1, TTF1, TXK

miRNA regulators (miRDB)

87 targeting SFTPB, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4261	99.59	70.30	3415

Literature-anchored findings (GeneRIF, showing 40)

• review of lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics (PMID:11699574)
• Data suggest that SMAD3 interactions with the positive regulators NKX2.1 and HNF-3 underlie the molecular basis for TGF-beta-induced repression of surfactant protein B gene transcription. (PMID:12161428)
• role of Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580 in disease (PMID:12356334)
• suggest that polymorphisms in intron 4 of the surfactant protein B gene independently modify the course of neonatal respiratory distress syndrome (PMID:12424586)
• An association between SP-B polymorphism and RDS was found in premature, first-born twins. In particular, the threonine allele was associated with an increased risk of RDS. (PMID:12483294)
• dimeric SP-B(1-25) is more efficient in restoring lung function in neonatal RDS and ARDS than monomeric SP-B(1-25) surfactant. (PMID:12490037)
• surfactant protein B expression is regulated by an enhancer region which binds to thyroid transcription factor-1, retinoic acid receptor, signal transducers and activators of transcription 3, nuclear receptor coactivators (SRC-1, ACTR, TIF2, and CBP/p300 (PMID:12573987)
• Mutataions and Polymorphisms in SFTPB is associated with severe unexplained respiratory distress (PMID:12784301)
• SP-B expression is regulated by PPARgamma in the lung (PMID:12829715)
• Reduced SP-B expression due to elevated nitric oxide levels can contribute to lung injury. (PMID:12896877)
• In human lungs, mature SP-B is involved in the structural organization of lamellar bodies and tubular myelin by the formation of core particles. (PMID:12972403)
• role of napsin A in the N- and C-terminal processing of pro-surfactant protein-B in type-II pneumocytes (PMID:13129928)
• The variant polymorphism of the SP-B gene is associated with ARDS and with direct pulmonary injury in women (PMID:14718442)
• Examination of different immunohistochemical marker SP-B is helpful in the diagnosis and differential diagnosis of pulmonary sclerosing hemangioma. (PMID:14720435)
• Current state of knowledge concerning the lung diseases associated with mutations in the SP-B and SP-C genes, and the potential roles of abnormal SP-B and SP-C expression and genetic variation in these genes in other lung diseases. Review. (PMID:14977415)
• The early postnatal fatal respiratory distress seen in SP-B-deficient children is combined with the near absence of active variants of surfactant protein C (SP-C). (PMID:15049696)
• most premature infants requiring continued respiratory support after 7 d of age experience transient episodes of dysfunctional surfactant that are associated with a deficiency of SP-B and SP-C. (PMID:15496605)
• Comparison of structural features of surfactant protein B (SP-B) C-terminal fragment in sodium dodecyl sulfate detergent micelles and hexafluoro-2-propanol provides clues about the role of anionic lipid headgroups in defining the structure of SP-B. (PMID:15568810)
• mapping the fusogenic and lytic domains of SP-B and assess the effects of altered fusion and lysis on surface activity (PMID:15654742)
• Results describe surfactant-associated protein B kinetics and synthesis in newborn infants, as measured by stable isotope technology (PMID:15695595)
• Intron 4 length variants affect SP-B mRNA splicing, and that this may contribute to lung disease. (PMID:15790313)
• Immuno-analysis of the hydrophobic surfactant proteins and their precursor forms in bronchoalveolar lavage is minimally invasive and can give valuable clues for the involvement of processing abnormalities in pediatric pulmonary disorders. (PMID:16042774)
• treatment with TGF-beta1 dose-dependently repressed Sftpb promoter activity in vitro, and a novel TGF-beta-responsive region in the Sftpb promoter was identified. (PMID:16100012)
• ceramide inhibited basal and dexamethasone induced SP-B mRNA levels in lung epithelial cells; inhibition was associated with inhibition of SP-B promoter activity and with inhibition of DNA binding activity of TTF-1 (PMID:16183668)
• biophysical analysis of structure-function determinants within the N-terminal region of pulmonary surfactant protein SP-B (PMID:16214863)
• Data are consistent with the view that an indel mutation occurred on a relatively common SFTPB haplotype. (PMID:16333843)
• PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of surfactant protein B, a protein required for lung function (PMID:16461352)
• We conclude that the described SNP causes differences in SP-B transcriptional activity and thus may contribute to individually different SP-B mRNA levels (PMID:16500948)
• Via promoter mutation analysis, adjacent TTF-1 binding sites within the proximal promoter region of SP-C were found to be essential for TTF-1/TAP26-enhanced SP-C promoter activity. (PMID:16630564)
• Single Nucleotide Polymorphism in Surfactant Protein B gene is associated with Chronic obstructive pulmonary disease (PMID:16971405)
• Differences in amounts of SP-B resulting from the promoter single nucleotide polymorphism could affect the clinical presentation of pulmonary disease. (PMID:17071721)
• We demonstrate that SP-A, SP-B, and SP-D are expressed in human nasal mucosa and cultured normal human nasal epithelial cells. (PMID:17209137)
• Possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. (PMID:17498296)
• This is the first study to detect and characterize SP-B in human sinus mucosa. Furthermore, SP-B is significantly up-regulated in cystic fibrosis chronic rhinosinusitis. (PMID:17507829)
• T/C mutation in exon 4 of SFPB does not translate into altered pulmonary function in young men (PMID:17540055)
• Analysis of the SP-B polymorphism G/C at nucleotide 8714 showed that among white neonates the GG genotype was found only in the RDS group at a frequency of 17% and the GC genotype was more frequently found in healthy term newborns. (PMID:17581675)
• Excess low-frequency variation, intragenic recombination and lack of common disruptive exonic variants favor complete resequencing for genetic association studies to identify regulatory SFTPB variants that cause neonatal respiratory distress syndrome. (PMID:17597650)
• pepsinogen C has a role in SP-B proteolytic processing in alveolar type 2 cells (PMID:18256027)
• In Systemic sclerosis, where massive fibrosis occurs, possession of the T/T genotype in the SP-B gene would reduce the risk of ILD in Japanese. (PMID:18263595)
• Determined population-based frequencies of SP-B mutations in newborn respiratory distress syndrome. (PMID:18317237)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sftpbb	ENSDARG00000067566
danio_rerio	sftpba	ENSDARG00000094708
mus_musculus	Sftpb	ENSMUSG00000056370
rattus_norvegicus	Sftpb	ENSRNOG00000010761
drosophila_melanogaster	Sap-r	FBGN0000416
caenorhabditis_elegans		WBGENE00004995

Paralogs (2): PSAPL1 (ENSG00000178597), PSAP (ENSG00000197746)

Protein

Protein identifiers

Pulmonary surfactant-associated protein B — P07988 (reviewed: P07988)

Alternative names: 18 kDa pulmonary-surfactant protein, 6 kDa protein, Pulmonary surfactant-associated proteolipid SPL(Phe)

All UniProt accessions (3): P07988, H0Y7V6, U3KQT2

UniProt curated annotations — full annotation on UniProt →

Function. Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of palmitic acid to nearly 70 millinewtons per meter.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Secreted. Extracellular space. Surface film.

Disease relevance. Pulmonary surfactant metabolism dysfunction 1 (SMDP1) [MIM:265120] A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. 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. A variation Ile to Thr at position 131 influences the association between specific alleles of SFTPA1 and respiratory distress syndrome in premature infants.

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).

RefSeq proteins (3): NP_000533, NP_001354210, NP_942140 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003119	SAP_A	Domain
IPR007856	SapB_1	Domain
IPR008138	SapB_2	Domain
IPR008139	SaposinB_dom	Domain
IPR008373	Saposin	Family
IPR011001	Saposin-like	Homologous_superfamily
IPR051428	Sphingo_Act-Surfact_Prot	Family

Pfam: PF02199, PF03489, PF05184

UniProt features (32 total): disulfide bond 10, sequence variant 6, domain 4, helix 3, propeptide 2, sequence conflict 2, glycosylation site 2, signal peptide 1, chain 1, strand 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
1DFW	INFRARED SPECTROSCOPY
1KMR	SOLUTION NMR
1RG3	SOLUTION NMR
1RG4	SOLUTION NMR
1SSZ	INFRARED SPECTROSCOPY
2DWF	SOLUTION NMR
2JOU	SOLUTION NMR
2M0H	SOLUTION NMR
2M1T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07988-F1	73.31	0.17

Functional residue map

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

Disulfide bonds (10): 69–143, 72–137, 100–112, 208–277, 211–271, 235–246, 248, 299–366, 302–360, 325–335

Glycosylation sites (2): 129, 311

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5683826	Surfactant metabolism
R-HSA-5688031	Defective pro-SFTPB causes SMDP1 and RDS
R-HSA-5688849	Defective CSF2RB causes SMDP5
R-HSA-5688890	Defective CSF2RA causes SMDP4

MSigDB gene sets: 176 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOCC_SECRETORY_GRANULE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOCC_COATED_VESICLE, NAKAMURA_LUNG_CANCER_DIFFERENTIATION_MARKERS, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GOBP_LIPID_METABOLIC_PROCESS, chr2p11, MODULE_397, GOBP_MEMBRANE_LIPID_METABOLIC_PROCESS, MCDOWELL_ACUTE_LUNG_INJURY_DN

GO Biological Process (4): sphingolipid metabolic process (GO:0006665), respiratory gaseous exchange by respiratory system (GO:0007585), animal organ morphogenesis (GO:0009887), lipid metabolic process (GO:0006629)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), multivesicular body (GO:0005771), endoplasmic reticulum membrane (GO:0005789), lamellar body (GO:0042599), clathrin-coated endocytic vesicle (GO:0045334), alveolar lamellar body (GO:0097208), multivesicular body lumen (GO:0097486), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with surfactant metabolism	3
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lipid metabolic process	1
multicellular organismal process	1
anatomical structure morphogenesis	1
animal organ development	1
primary metabolic process	1
binding	1
lytic vacuole	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
lamellar body	1
multivesicular body	1
late endosome lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

882 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFTPB	SFTPC	P11686	991
SFTPB	SFTPA2	P07714	985
SFTPB	ABCA3	Q99758	959
SFTPB	SFTPD	P35247	947
SFTPB	X6REF7	X6REF7	935
SFTPB	NKX2-1	P43699	904
SFTPB	SCGB1A1	P11684	800
SFTPB	FOXF1	Q12946	746
SFTPB	MBL2	P11226	729
SFTPB	P3H3	Q8IVL6	693
SFTPB	AQP5	P55064	671
SFTPB	FOXF2	Q12947	670
SFTPB	CSF2RA	P15509	668
SFTPB	SLC23A1	Q9UHI7	662
SFTPB	SLC23A2	Q9UGH3	660

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SFTPB	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
SFTPB	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): SFTPB (Two-hybrid), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS), SFTPB (Proximity Label-MS)

ESM2 similar proteins: A0JNB3, A5PJC7, A6NGW2, B1AWI6, O02708, O46641, O70540, O94772, P07988, P09919, P09920, P10960, P15285, P15781, P17129, P17813, P19794, P22355, P22749, P27106, P37176, P40967, P49000, P50405, P51500, P51693, Q06154, Q29075, Q49LS3, Q4R5M8, Q5GH66, Q60696, Q61207, Q61826, Q6NUJ1, Q6PL45, Q6PX77, Q6UX68, Q6ZUA9, Q7RTU9

Diamond homologs: O13035, P07602, P07988, P10960, P20097, P26779, P81405, Q61207, Q6NUJ1, Q8C1C1, P15285, P15781, P15782, P17129, P22355, P50405

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TGFB1	“down-regulates quantity by repression”	SFTPB	“transcriptional regulation”
FOXA1	“up-regulates quantity by expression”	SFTPB	“transcriptional regulation”
NKX2-1	“up-regulates quantity by expression”	SFTPB	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	9
Uncertain significance	105
Likely benign	59
Benign	35

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
13201	NM_000542.5(SFTPB):c.361delinsGAA (p.Pro121fs)	Pathogenic
13202	NM_000542.5(SFTPB):c.365del (p.Leu122fs)	Pathogenic
13203	SFTPB, 1-BP DEL, 457C	Pathogenic
13205	NM_000542.5(SFTPB):c.465G>T (p.Gly155=)	Pathogenic
1418303	NM_000542.5(SFTPB):c.876G>A (p.Trp292Ter)	Pathogenic
1691339	NM_000542.5(SFTPB):c.146G>A (p.Cys49Tyr)	Pathogenic
1752055	NM_000542.5(SFTPB):c.581del (p.Gln194fs)	Pathogenic
1761177	NM_000542.5(SFTPB):c.754C>T (p.Arg252Cys)	Pathogenic
1766142	NM_000542.5(SFTPB):c.883C>T (p.Arg295Ter)	Pathogenic
3062403	GRCh37/hg19 2p11.2(chr2:85860694-85917890)x1	Pathogenic
587605	NM_000542.5(SFTPB):c.1084-1G>A	Pathogenic
631868	NM_000542.5(SFTPB):c.361_362insAA (p.Pro121fs)	Pathogenic
1766887	NM_000542.5(SFTPB):c.904T>G (p.Cys302Gly)	Likely pathogenic
2433325	NM_000542.5(SFTPB):c.479del (p.Leu160fs)	Likely pathogenic
2627672	NM_000542.5(SFTPB):c.324dup (p.Met109fs)	Likely pathogenic
2629885	NM_000542.5(SFTPB):c.583-1G>T	Likely pathogenic
2633519	NM_000542.5(SFTPB):c.268-2del	Likely pathogenic
2734240	NM_000542.5(SFTPB):c.195+4A>G	Likely pathogenic
2897901	NM_000542.5(SFTPB):c.195+1G>A	Likely pathogenic
4280031	NM_000542.5(SFTPB):c.439C>T (p.Gln147Ter)	Likely pathogenic
978726	NM_000542.5(SFTPB):c.730G>A (p.Gly244Ser)	Likely pathogenic

SpliceAI

1520 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85663658:GCTCA:G	donor_loss	1.0000
2:85663659:CTCAC:C	donor_loss	1.0000
2:85663660:TCA:T	donor_loss	1.0000
2:85663661:CACT:C	donor_loss	1.0000
2:85663662:A:AC	donor_gain	1.0000
2:85663663:C:CC	donor_gain	1.0000
2:85663844:CACC:C	acceptor_gain	1.0000
2:85663846:CC:C	acceptor_gain	1.0000
2:85663847:CC:C	acceptor_gain	1.0000
2:85666616:CAGT:C	donor_gain	1.0000
2:85667101:ATTAC:A	donor_loss	1.0000
2:85667103:TACC:T	donor_loss	1.0000
2:85667104:A:C	donor_loss	1.0000
2:85667105:CCTG:C	donor_loss	1.0000
2:85667178:C:CC	acceptor_gain	1.0000
2:85662110:C:CC	acceptor_gain	0.9900
2:85663663:CT:C	donor_gain	0.9900
2:85663681:T:TA	donor_gain	0.9900
2:85663843:GCACC:G	acceptor_gain	0.9900
2:85663844:CACCC:C	acceptor_gain	0.9900
2:85663845:ACC:A	acceptor_gain	0.9900
2:85663846:CCC:C	acceptor_gain	0.9900
2:85663848:C:CA	acceptor_loss	0.9900
2:85663848:C:CC	acceptor_gain	0.9900
2:85663848:C:T	acceptor_gain	0.9900
2:85663849:T:C	acceptor_loss	0.9900
2:85663854:C:CT	acceptor_gain	0.9900
2:85663860:C:CT	acceptor_gain	0.9900
2:85665600:CCTCA:C	donor_loss	0.9900
2:85665601:CTCAC:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010266 (2:85669392 G>A), RS1000062910 (2:85669662 C>G), RS1000118895 (2:85668330 C>G), RS1000241702 (2:85663791 G>A,T), RS1000373667 (2:85657863 T>C), RS1000847057 (2:85662210 C>G,T), RS1001068933 (2:85668247 G>A,C,T), RS1001288624 (2:85669296 A>C), RS1001341615 (2:85662565 G>A), RS1001516388 (2:85657226 C>T), RS1001586761 (2:85657529 C>T), RS1001637675 (2:85663790 C>A,T), RS1001917615 (2:85665451 C>G,T), RS1001932742 (2:85657820 A>C,G), RS1001974773 (2:85665148 G>A,T)

Disease associations

OMIM: gene MIM:178640 | disease phenotypes: MIM:265120

GenCC curated gene-disease

Disease	Classification	Inheritance
surfactant metabolism dysfunction, pulmonary, 1	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
surfactant metabolism dysfunction, pulmonary, 1	Definitive	AR

Mondo (2): surfactant metabolism dysfunction, pulmonary, 1 (MONDO:0009929), hereditary pulmonary alveolar proteinosis (MONDO:0012580)

Orphanet (2): Neonatal acute respiratory distress syndrome (Orphanet:217563), Hereditary pulmonary alveolar proteinosis (Orphanet:264675)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000765	Abnormal thorax morphology
HP:0000961	Cyanosis
HP:0001217	Clubbing
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001622	Premature birth
HP:0001649	Tachycardia
HP:0001662	Bradycardia
HP:0001667	Right ventricular hypertrophy
HP:0001695	Cardiac arrest
HP:0002090	Pneumonia
HP:0002092	Pulmonary arterial hypertension
HP:0002094	Dyspnea
HP:0002104	Apnea
HP:0002113	Pulmonary infiltrates
HP:0002615	Hypotension
HP:0002643	Neonatal respiratory distress
HP:0002789	Tachypnea
HP:0002878	Respiratory failure
HP:0003623	Neonatal onset
HP:0003811	Neonatal death
HP:0004876	Spontaneous neonatal pneumothorax
HP:0005942	Desquamative interstitial pneumonitis
HP:0006515	Interstitial pneumonitis
HP:0006517	Intraalveolar phospholipid accumulation
HP:0006528	Chronic lung disease
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0011947	Respiratory tract infection
HP:0012418	Hypoxemia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1139	Blood protein levels	3.000000e-189

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535832	Pulmonary alveolar proteinosis, congenital (supp.)
C566882	Surfactant Metabolism Dysfunction, Pulmonary, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Dexamethasone	affects cotreatment, increases expression, increases stability, decreases reaction	4
nitrofen	decreases expression, decreases reaction	2
Resveratrol	affects cotreatment, decreases expression	2
Ascorbic Acid	decreases expression, decreases reaction	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
lead acetate	decreases expression	1
titanium dioxide	increases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases expression	1
didecyldimethylammonium	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
pyrazolanthrone	decreases expression, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Acetylcysteine	decreases expression, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Chromium	affects response to substance	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	increases expression	1
Hydrocortisone	increases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Malathion	decreases expression	1
Manganese	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_WN80	SP212	Induced pluripotent stem cell	Female
CVCL_WN81	SP212Corr	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01511068	PHASE2	COMPLETED	Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP)
NCT05761899	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of PMT Therapy of hPAP