SERPINB4

Chr 18

serpin family B member 4

Also known as: LEUPIN, PI11, SCCA-2, SCCA1, SCCA2

NCBI Gene: 6318ENSG00000206073UniProt: P48594

This protein inhibits serine proteases including granzyme M, which normally kills tumor cells, and modulates immune responses. Mutations cause autosomal recessive severe dermatitis with multiple allergies and metabolic wasting (SAM syndrome), characterized by early-onset severe skin inflammation, food allergies, and failure to thrive. The gene is extremely intolerant to loss-of-function variants, indicating it is highly constrained and essential for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
11
Pubs (1 yr)
98
P/LP submissions
0%
P/LP missense
1.88
LOEUF
DN
Mechanism· predicted
Clinical Summary— SERPINB4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
95 unique Pathogenic / Likely Pathogenic· 78 VUS of 184 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
1.88LOEUF
pLI 0.000
Z-score -1.46
OE 1.41 (0.99–1.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.87Z-score
OE missense 1.37 (1.24–1.51)
279 obs / 203.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.41 (0.99–1.88)
0≤0.351.4
Missense OE1.37 (1.24–1.51)
0≤0.61.4
Synonymous OE1.45
0≤1.21.6
LoF obs/exp: 21 / 14.9Missense obs/exp: 279 / 203.7Syn Z: -3.14
DN
0.81top 10%
GOF
0.6247th %ile
LOF
0.1895th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

184 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic7
VUS78
Likely Benign9
88
Pathogenic
7
Likely Pathogenic
78
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
88
0
88
Likely Pathogenic
0
0
7
0
7
VUS
0
71
7
0
78
Likely Benign
0
9
0
0
9
Benign
0
0
0
0
0
Total0801020182

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINB4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients