SFTPC

Chr 8AD

surfactant protein C

Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces

Primary Disease Associations & Inheritance

Surfactant metabolism dysfunction, pulmonary, 2MIM #610913
AD
UniProtPulmonary surfactant metabolism dysfunction 2
3
Active trials
61
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.25
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySFTPC
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Gene-Disease Validity (ClinGen)
SFTPC- related interstitial lung disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.001
Z-score 1.04
OE 0.64 (0.351.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.85Z-score
OE missense 0.78 (0.660.93)
90 obs / 115.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.351.25)
00.351.4
Missense OE0.78 (0.660.93)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 6 / 9.4Missense obs/exp: 90 / 115.7Syn Z: -1.02
DN
0.6358th %ile
GOF
0.5661th %ile
LOF
0.2484th %ile

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

DNprediction above median · 1 literature citation
GOF1 literature citation

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.

Literature Evidence

DNIn studies of transfected human lung cancer cells, Wang et al. (2003) demonstrated that the 460+1G-A mutation resulted in the diversion of both mutant and wildtype unprocessed proSPC to aggresomes, consistent with a dominant-negative effect.PMID:12538769
GOFMore plausible, the data suggest that SP-C mutations induce a toxic gain of function that is a consequence of the resultant abnormalities in protein trafficking.PMID:15557112

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SFTPC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗