SERPINB9

Chr 6

serpin family B member 9

Also known as: CAP-3, CAP3, PI-9, PI9

NCBI Gene: 5272ENSG00000170542UniProt: P50453

This gene encodes a member of the serine protease inhibitor family which are also known as serpins. The encoded protein belongs to a subfamily of intracellular serpins. This protein inhibits the activity of the effector molecule granzyme B. Overexpression of this protein may prevent cytotoxic T-lymphocytes from eliminating certain tumor cells. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2012]

120
ClinVar variants
52
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— SERPINB9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 63 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.012
Z-score 1.87
OE 0.42 (0.22–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.01Z-score
OE missense 1.00 (0.89–1.12)
218 obs / 218.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.22–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.89–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 5 / 12.0Missense obs/exp: 218 / 218.3Syn Z: 0.72

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic5
VUS63
Likely Benign5
47
Pathogenic
5
Likely Pathogenic
63
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
47
0
47
Likely Pathogenic
0
0
5
0
5
VUS
0
58
5
0
63
Likely Benign
0
3
1
1
5
Benign
0
0
0
0
0
Total061581120

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINB9 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response.
Jiang P et al.·Nat Med
2018
Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial.
Liao M et al.·Endocrine
2024
SERPINB9 is commonly amplified and high expression in cancer cells correlates with poor immune checkpoint blockade response.
Ibáñez-Molero S et al.·Oncoimmunology
2022
Reduced serpinB9-mediated caspase-1 inhibition can contribute to autoinflammatory disease.
van der Burgh R et al.·Oncotarget
2016
Overexpression of an Engineered SERPINB9 Enhances Allogeneic T-cell Persistence and Efficacy.
Teo PY et al.·Cancer Immunol Res
2024
Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer.
Peters FS et al.·Clin Exp Immunol
2019Clinical trial
Identification of genes with abnormal expression changes in acute myeloid leukemia.
Stirewalt DL et al.·Genes Chromosomes Cancer
2008
Differential gene expression patterns and interaction networks in BCR-ABL-positive and -negative adult acute lymphoblastic leukemias.
Juric D et al.·J Clin Oncol
2007
Quercetin supplementation and its effect on human monocyte gene expression profiles in vivo.
Boomgaarden I et al.·Br J Nutr
2010
The novel role of SERPINB9 in cytotoxic protection of human mesenchymal stem cells.
El Haddad N et al.·J Immunol
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SerpinB9 sustains CIITA to orchestrate MHC-II expression and Th1 differentiation in β-glucan-induced macrophages.
Huang X et al.·Immunol Res
2025
Biomimetic self-assembly nanoparticles inhibit serpinB9 and synergistically enhance COD-induced ferroptosis for cancer therapy.
Han R et al.·Mater Today Bio
2025🔓 Open Access
Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance.
Huang H et al.·Nat Commun
2025
Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma.
Yan W et al.·Nat Commun
2025🔓 Open Access
Single-cell landscape identified SERPINB9 as a key player contributing to stemness and metastasis in non-seminomas.
Bian Z et al.·Cell Death Dis
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools