SFTPB

Chr 2

surfactant protein B

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

NCBI Gene: 6439 ENSG00000168878 UniProt: P07988

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPulmonary surfactant metabolism dysfunction 1

UniProtRespiratory distress syndrome in premature infants

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · surfactant metabolism dysfunction, pulmonary, 1 · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in SFTPB?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

475 rare PASS variants

Rare truncating (LoF)

1 in 870

69 rare PASS variants

Rare synonymous (reference)

1 in 170

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SFTPB. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 750
South Asian	~43k	1 in 94	1 in 2,800
Remaining (unassigned)	~30k	1 in 77	1 in 2,200
European (Finnish)	~27k	1 in 320	≈ 1 in 26,000
Admixed American	~22k	1 in 84	1 in 1,300
African / African American	~21k	1 in 76	1 in 1,300
East Asian	~20k	1 in 110	1 in 2,800
Ashkenazi Jewish	~13k	1 in 620	1 in 2,200
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓