SERPINB3

Chr 18

serpin family B member 3

Also known as: HsT1196, SCC, SCCA-1, SCCA-PD, SCCA1, SSCA1, T4-A

NCBI Gene: 6317ENSG00000057149UniProt: P29508

The protein functions as a cysteine protease inhibitor that modulates immune responses and inhibits UV-induced apoptosis by suppressing JNK1 activity. SERPINB3 mutations cause autosomal recessive intellectual disability with seizures and hypotonia, typically presenting in early childhood. The gene shows very low constraint against loss-of-function variants (high LOEUF score), consistent with recessive inheritance where heterozygous carriers are unaffected.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
27
Pubs (1 yr)
98
P/LP submissions
0%
P/LP missense
1.86
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SERPINB3
⚡
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· 64 VUS of 178 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
1.86LOEUF
pLI 0.000
Z-score -1.28
OE 1.36 (0.95–1.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.66Z-score
OE missense 1.32 (1.20–1.46)
277 obs / 209.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.36 (0.95–1.86)
0≤0.351.4
Missense OE1.32 (1.20–1.46)
0≤0.61.4
Synonymous OE1.32
0≤1.21.6
LoF obs/exp: 20 / 14.7Missense obs/exp: 277 / 209.3Syn Z: -2.28
DN
0.81top 10%
GOF
0.6735th %ile
LOF
0.1894th %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
GOFprediction 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

178 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic7
VUS64
Likely Benign11
Benign2
88
Pathogenic
7
Likely Pathogenic
64
VUS
11
Likely Benign
2
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
57
7
0
64
Likely Benign
0
10
0
1
11
Benign
0
2
0
0
2
Total0691021172

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINB3 · protein map & ClinVar variants

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

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