SFTPB

Chr 2AR

surfactant protein B

Also known as: PSP-B, SFTB3, SFTP3, SMDP1, SP-B

NCBI Gene: 6439 ENSG00000168878 UniProt: P07988 OMIM: 178640

Surfactant protein B is an amphipathic protein that reduces surface tension at the air-liquid interface in alveoli and enhances the spreading and stability of pulmonary surfactant monolayers essential for lung function after birth. Mutations cause surfactant metabolism dysfunction type 1 (pulmonary alveolar proteinosis due to surfactant protein B deficiency), which presents with fatal respiratory distress in the neonatal period. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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.[provided by RefSeq, Feb 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.721 OMIM phenotype

Clinical Summary— SFTPB

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Gene-Disease Validity (ClinGen)

surfactant metabolism dysfunction, pulmonary, 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

20 unique Pathogenic / Likely Pathogenic· 105 VUS of 255 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 2.59

OE 0.42 (0.26–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.60Z-score

OE missense 0.89 (0.79–1.00)

202 obs / 227.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.26–0.72)

0≤0.351.4

Missense OE?0.89 (0.79–1.00)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 10 / 23.6Missense obs/exp: 202 / 227.3Syn Z: 0.49

This gene — mechanism propensity

0.75top 25%

GOF

0.77top 25%

LOF

0.1993th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

255 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic9

VUS105

Likely Benign69

Benign35

Conflicting19

Pathogenic

Likely Pathogenic

105

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	2	1	1	11
Likely Pathogenic	6	2	1	0	9
VUS	1	84	18	2	105
Likely Benign	0	12	25	32	69
Benign	0	4	28	3	35
Conflicting	—				19
Total	14	104	73	38	248

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap SFTPB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →